TR NG I H C C N TH

KHOA KHOA H C B MN HA

B C U TM HI U THNH PH N HA H C C A NH A T D U CY M U (Calophyllum inophyllum L.)

LU N VN T T NGHI P I H C

CN B

Ths. Th M Linh

H NG D N

SINH VIN TH C HI N
L p: C Nhn Ha K31

L Minh Vng - 2052021

C n Th, thng 05/2009

Lu n vn t t nghi p

CBHD: Th M Linh

L I C M N
c h c h i r t nhi u ki n th c v nh ng kinh nghi m qu bu. cng l Sau th i gian h c t p v rn luy n d i mi tr ng i H c C n Th, em

nh cng n c a qu th y c d y d v truy n t nh ng ki n th c y cho em, gip em c c nh ng hnh trang c n thi t v ng tin trn con ng l p nghi p sau ny.

H c, khoa Khoa H c, tr ng i H c C n Th.

Em xin g i l i c m n chn thnh n t t c qu th y c b mn Ha c bi t, em xin g i l i c m n chn thnh v su s c nh t n c Th

M Linh, ng i d c h t lng nhi t tnh v s t n tm c a mnh gip em hon thnh t t ti lu n vn t t nghi p. Em xin chn thnh c m n qu th y c b mn Mi Tr ng Khoa Mi

Tr ng v Ti Nguyn Thin Nhin, tr ng i H c C n Th t o i u ki n thu n l i gip em hon thnh ti ny. ng th i, con xin by t lng bi t n su s c i v i gia nh nh ng

ng i lun bn con, ng vin v gip con trong su t th i gian th c hi n lu n vn t t nghi p. th i gian qua.

Ngoi ra, ti xin c m n cc b n c a ti, cc b n gip ti trong su t Xin chn thnh c m n!

SVTH: L Minh Vng

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CBHD: Th M Linh

TR NG I H C C N TH KHOA KHOA H C B MN HA H C

C NG HA X H I CH NGHA VI T NAM c l p T do H nh phc

1. Cn b h ng d n: ThS. Th M Linh 2. ti: B c u tm hi u thnh ph n ha h c c a nh a t d u cy m u (Calophyllum inophyllum L.) 3. Sinh vin th c hi n: L Minh Vng MSSV: 2052021 4. L p: C nhn ha h c. Kha 31 5. N i dung nh n xt: a. Nh n xt v hnh th c c a lu n vn t t nghi p ............................................................................................................................... .............................................................................................................. . ............................................................................................................................... b. Nh n xt v n i dung c a lu n vn t t nghi p ( ngh ghi chi ti t y ) nh gi n i dung th c hi n c a ti: ............................................................................................................................... ............................................................................................................................... ............................................................................................................................... Nh ng v n cn h n ch : ............................................................................................................................... ............................................................................................................................... ............................................................................................................................... c. Nh n xt i v i t ng sinh vin tham gia th c hi n ti (ghi r t ng n i dung chnh do sinh vin no ch u trch nhi m th c hi n n u c): ............................................................................................................................... ............................................................................................................................... ............................................................................................................................... d. K t lu n, ngh v i m: ............................................................................................................................... ............................................................................................................................... ............................................................................................................................... C n Th, ngy
Cn b h ng d n

NH N XT NH GI C A CN B

H NG D N

thng

nm 2009

Th M Linh
SVTH: L Minh Vng

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PH N I: T NG QUAN..................................................................................................1 Chng 1: M

M CL C

Chng 2: T NG QUAN V CY M U...............................................................3

U...................................................................................................2

2.1. GI I THI U CHUNG V CY M U [1,2,4,10,11,15] ..................................... 4 2.1.1. Ngu n g c cy m u ................................................................................... 4 2.1.2. Danh php v phn lo i............................................................................... 4 Tn khoa h c: Calophyllum inophyllum L............................................................ 4 2.1.3. c i m th c v t ....................................................................................... 5 2.1.4. Sinh thi v phn b .................................................................................... 6 2.1.5. Cng d ng [1,6,7] ......................................................................................... 6

2.2. THNH PH N HA H C C A CY M U ................................................ 9 2.2.2. Thnh ph n ha h c c a thn cy [17] ........................................................ 9

2.1.8. Hnh nh v cy m u ................................................................................. 8

2.1.6. Cc bi thu c dn gian s d ng m u [25] .................................................. 7

2 .2.1. Thnh ph n ha h c c a l[9,14,16,18,19,20] ................................................ 9 2.2.2.1. Thnh ph n ha h c c a li cy.......................................................... 9 2.2.2.2. Thnh ph n ha h c c a g cy (timber)........................................... 10 2.2.2.3. Thnh ph n ha h c c a v cy......................................................... 10

2.2.3. Thnh ph n ha h c c a v r [21] ........................................................... 10 2.2.4. Thnh ph n ha h c c a d u th [2,9,10] ................................................... 11 2.2.4.1. Friedelin .......................................................................................... 11

2.2.4.2. Cc d n xu t c a coumarin ............................................................. 11 2.2.4.4. Cc acid bo, glycerides, sterols v ba nhm lipid ......................... 13 2.2.4.5. Ngoi ra, d u m u cn ch a cc tnh ch t terpenic, benzoic, v

2.2.4.3. Nhm Xanthone .............................................................................. 12

2.3. TNH CH T V T L V HA H C C A D U M U [2] ....................... 15 2.4. TC D NG C A CC CH T C TRONG D U M U [2] ....................... 15

oxibenzoic acid, m t ph n nh vitamin F....................................................... 15

SVTH: L Minh Vng

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2.4.1. Cc d n xu t c a coumarin ....................................................................... 15

2.4.2. Nhm Xanthone:....................................................................................... 16

2.4.3. Friedelin .................................................................................................... 16

2.5. TC D NG D C L C A D U M U [2,7,22,23,25,27,28]........................ 16 2.5.1. c tnh..................................................................................................... 16 2.5.3. 2.5.2. Tc d ng c a d u m u i v i c th ...................................................... 17

2.4.4. Cc acid bo .............................................................................................. 16

Chng 3: PHNG PHP CHI T XU T [1] .............................................................. 19

2.6. GI TR KINH T C A D U M U ....................................................... 18

ng d ng c a d u m u ............................................................................ 17

3.1. C S C A PHNG PHP CHI T .......................................................... 19 3.2. YU C U C A DUNG MI KHI CHI T .................................................... 19 3.3.1. Chi t b ng phng php ng m ki t (Percolation) .................................... 21 3.3. CC PHNG PHP CHI T XU T ........................................................... 20 3.3.2. Chi t b ng phng php ngm d m(Maceration) .................................... 21 3.3.4. Chi t b ng Soxhlet .................................................................................... 22 3.3.5. Chi t b ng cch un hon lu ................................................................... 22

3..3.3. Chi t b ng phng php ng m ki t ng c dng ..................................... 21

Chng 4: PHNG PHP S C K C T [1]................................................................ 24

3.3.6. Chi t b ng phng php li cu n hi n c .............................................. 23

4.1. S C K C T [4] ............................................................................................ 24 4.2. K THU T TRI N KHAI ............................................................................. 25

4.1.1 Nguyn t c ................................................................................................. 24 4.2.1. Chu n b c t .............................................................................................. 25 4.2.2. a ch t phn tch vo c t........................................................................ 26 H T TRI M U.............29 4.2.3. R a c t - cn c g i l gi i ly ch t ra kh i c t ..................................... 27

Chng 5: QUY TRNH C L P CC CH T T

5.1. QUY TRNH THAM KH O 1[6] ................................................................... 29

SVTH: L Minh Vng

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5.1. QUY TRNH THAM KH O 2[21] .................................................................. 31

PH N II: TH C NGHI M ........................................................................................ 35 Chng 1: PHNG TI N V PHNG PHP NGHIN C U....................36 1.1. PHNG TI N............................................................................................... 36

5.3. QUY TRNH THAM KH O 3[3] ................................................................... 33

1.2. PHNG PHP NGHIN C U ................................................................... 36 1.2.1. Phng php tch chi t ............................................................................. 36 1.2.2. Phn l p cc c u t h u c ....................................................................... 36

1.2.3. nh tnh .................................................................................................. 37 1.2.4. Xc nh c u trc ...................................................................................... 37 1.2.5. Quy trnh th c nghi m chi t tch v c l p cc h p ch t h u c c a nh a t d u m u.............................................................................................................. 38 D U TH................................................................. 41 CAO ETHANOL ..................... 41

Chng 2: TH C NGHI M ..................................................................................41 2.1. I U CH NH A T

2.2. NH TNH CAO ETHNOL S B B NG S C K B NG M NG ........ 41 2.3. QU TRNH I U CH COUMARIN T

2.4. S C K C T L N M T CAO BENZENE ........................................... 43 2.5. S C K C T L N 2 PHN O N C ................................................... 45 2.6. QU TRNH K T TINH V LM S CH ............................................... 47 V TH O LU N .................................................................... 49

PH N III: K T QU

KH O ST CH T THU C SAU QU TRNH C L P ...........................50

3.1. PHNG PHP ............................................................................................. 50

PH N IV: K T LU N V KI N NGH ..................................................................... 53 4.1.K T LU N....................................................................................................... 54 4.2.KI N NGH ...................................................................................................... 54

3.2. K T QU ........................................................................................................ 50

PH L C...................................................................................................................55 TI LI U THAM KH O ........................................................................................56

SVTH: L Minh Vng

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CBHD: Th M Linh

Hnh 1.1.1. Cy m u [16] ....................................................................................3 Hnh 1.1.2. Cy m u v tri .................................................................................4 Hnh 1.1.5. Cc cng nhn ang tch v tri m u l y nhn p d u [5] ..........8 Hnh 1.1.4. Hoa m u [4] ......................................................................................8 Hnh 1.1.6. Chi t xu t tinh d u m u theo tiu chu n Organic x ng c a cng ty

M C L C HNH

Chuyn Thin Nhin [5] ........................................................................................8 Hnh 2.1. S c k b ng m ng cao ethanol v i h gi i ly Benzene/EtOAc (9:1)..41

Hnh 2.2. S c k b ng m ng cao benzene v i h dung mi gi i ly Benzene/EtOAc Hnh 2.3. S c k c t cao benzene........................................................................44 (9:1) ......................................................................................................................44

Benzene/EtOAc (2:1)...........................................................................................46

Hnh 2.4. S c k b ng m ng phn o n C v i h dung mi gi i ly

Hnh 2.5. H dung mi n-hexane/EtOAc(2:1) ....................................................48

Hnh 2.6. H dung mi PE/EtOAc(2:1) ..............................................................48 Hnh 2.8. S c k l p m ng ch t A v i 3 h dung mi khc nhau......................48

Hnh 2.7. H dung mi .......................................................................................48

SVTH: L Minh Vng

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M C L C B NG
B ng 2.2. Cc thnh ph n chnh c trong cc acid bo B ng 2.1. Ba nhm lipid chnh c trong d u m u .............................................14 d u m u....................45

B ng 2.1. K t qu s c k c t cao benzene ..........................................................45 B ng 3.1. K t qu o ph IR ...............................................................................51 B ng 3.2. K t qu o ph IR h p ch t Calophylloid cng b .......................51 B ng 2.1. K t qu s c k c t phn o n C..........................................................47

SVTH: L Minh Vng

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T NG QUAN

PH N I

SVTH: L Minh Vng

Lu n vn t t nghi p

CBHD: Th M Linh

v ng d ng th c ti n phong ph trong m i lnh v c v i s ng c a con ng i. Ngoi ch t l ng g t t cy m u cn c xem nh m t ngu n ti nguyn cy m u t l, thn, r , tri, th m ch l b c a tri sau khi p l y d u u c tc d ng d c l. thu c qu m thin nhin ban t ng cho loi ng i. T t c cc b ph n c a cy

T hng nghn nm tr c cy m u c bi t n v i nh ng cng d ng

Chng 1: M

d u v tm cch ly trch dng vo vi c sn sc, b o v da ch ng l i cc tc nhn gy t n h i nh nh n ng, Qua kinh nghi m th c t , d u m u tr thnh phng thu c v m m cao, gi bi n.

T xa, ng i Tahiti s m khm ph ra nh ng h t m u kh c ch a

ph m dn gian chm sc b o v da, l s n ph m thin nhin gip ch ng n ng v

lm m da. V i nh ng tc d ng y, ng i ta ch b o v cy m u, thu hi h t v xem l mn qu t ng qu gi c a thin nhin. Ph n Tahiti dng d u m u hng ngy nh ch t lm m da, lm m ph m bi ln m t v thn th .

gn qu n l i lm nh ng ng n u c trong cng vi c ng n vo ban m.

Vi t Nam ng i dn cn s d ng tri m u c phi kh v dng bng

c a cy m u c tc d ng ch ng HIV-1; Nh ng vi sinh v t nh: S. aureus tropicalis (ATCC66029).

Qua nh ng nghin c u g n y cn cho th y nh ng ch t trong l, thn, r

(ATCC6538), V. angillarium (ATCC19264), E. coli (ATCC8739), v C. Cy m u c tn khoa h c l Calophyllum inophyllum L thu c hai h

Clusiaceae v Guttiferea. Nhng th c ch t th hai h ny ch khc nhau cao c a cy.

chi u

HI U THNH PH N HA H C C A NH A T

c a n. Do nn chng ti ti n hnh nghin c u ti: B C U TM D U CY M U

G n y, cy m u ang c quan tm nghin c u v tc d ng d c l

(Calophyllum inophyllum L ), xc nh thnh ph n ha h c.

SVTH: L Minh Vng

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CBHD: Th M Linh

Hnh 1.1. Cy m u [30]

SVTH: L Minh Vng

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CBHD: Th M Linh

2.1. GI I THI U CHUNG V CY M U [1,2,4,10,11,15]

2.1.1. Ngu n g c cy m u Cy m u c ngu n g c t vng Tahiti thu c

Chng 2: T NG QUAN V

CY M U

Nam . c bi t n c nhi u

Hawaii v c. Cy m u c ng i dn Polynesia r t sng bi v c nh c c xu t hi n r ng ri cc siu th

vng o Polynesia. Sau n c du nh p n

n , thu c vng b n a

n trong cc bi thnh ca c a ng i Hawaii. T m t vi nm tr c, d u m u kh p ni trn th gi i Chu u v M . Ngy nay, cy m u c tr ng nh ng qu c gia kh h u nhi t i gi ma.

Hnh 1.1.2. Cy m u v tri [29]

2.1.2. Danh php v phn lo i

Tn khoa h c: Calophyllum inophyllum L. Tn th ng: Cy m u. Tn n c ngoi: Alexandrian laurel, beach mahogany, beauty leaf, poon,

Btaches (Palau); Daog, daok (Guam, N. Marianas); Dilo (Fiji); Eet (Kosrae); Fetau (Tonga); Fetau (Samoa); Isou (Pohnpei); Kamani, kamanu (Hawaii);

oil nut tree (Anh); Beach calophyllum (Papua New Guinea); Biyuch (Yap);

SVTH: L Minh Vng

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CBHD: Th M Linh

Lueg (Marshalls); Rakich (Chuuk); Tamanu (Cook Islands, Society Islands, Marquesas); Te itai (Kiribati); Phn lo i: Gi i: Plantae

Ngnh: Magnoliophyta

L p: Magnoliopsida

H : Clusiaceae, Guttiferae Chi: Calophyllum

Phn h : Kielmeyeroideae Loi: inophyllum L

2.1.3. c i m th c v t

chi u cao, cn nh ng c i m khc chng tng t nhau.

Cy m u c hai h l Clusiacee v Guttiferea. Chng ch khc nhau v Cy m u cao 8 20 m ( i v i h Clusiaceae) v cao 10 15 m ho c 25

30 m ( i v i h Guttiferae, ty theo kh h u t ng vng m chng c chi u cao khc nhau), ng knh trung bnh 30 35 cm. Cnh non nh n, trn, tng i ng n ch kho ng 2 3 m. L m u mu xanh, bng lng, hnh b u d c. L l n, m c i, thon di,

m ng, gn ph nhi u, nh , song song v g n nh th ng gc v i gn chnh, n i r c hai m t, cu ng l dy v b t. Cy m u c hoa to kho ng 25 mm, m c thnh chm v c ki u pht hoa

hnh chy, m i chm t 4 15 hoa, thng th ng l 9 hoa, hoa c mu tr ng ho c vng cam. C 4 i l, m i hoa c 4 cnh, nhi u nh x p thnh 4 6 b, b u m t l non v i m t non nh g c, 1 vi nh y. Qu m u c d ng hnh trn, kch c gi ng nh qu m, ng knh kho ng

2 4 cm, mu xanh, da trn, v m ng, bn trong h t mu vng nh t c b c b i m t l p mu xm. Khi chn, qu m u chuy n t t sang mu vng r i cu i cng l mu nu. Cy ra hoa thng 2 6, c qu thng 10 12.

SVTH: L Minh Vng

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CBHD: Th M Linh

2.1.4. Sinh thi v phn b m u th ng pht tri n

Do cy m u c tnh ch t thch h p v i kh h u nhi t i gi ma nn cy vng duyn h i v pht tri n t t nh t nhi u vng c cao v a ph i. r ng t th p.

Tuy nhin n cng c tr ng

h i, t st v k c t thoi ha.

Cy m u c kh nng ch u ng nhi u lo i t tr ng: t ct mi n duyn nhi u qu c gia khc nhau nh: Thi n , Sri Lanka, v

Lan, Vi t Nam, Myanmar, Malaysia, Nam Melanesia v Polynesia, 2.1.5. Cng d ng [1,6,7]

Hi n nay, cy m u c th tm th y

nhi u o c a

ng k v m t d c l v kinh t . Theo kinh nghi m dn gian:

T t c cc b ph n c a cy m u (d u, l, thn cy, g ), u c cng d ng

Polynesian dng d u trch t h t c a tri m u th p sng cho n, ngoi ra n cng c th c dng trong vi c d ng da, lm d u d ng tc, d u thm, b. Nh a m u c v m n, tnh r t l nh, c tc d ng gy nn, gi i cc lo i

a. Tri chn c tc d ng lm gi m sng t y do b mu i t. Ng i dn

ng c, b ng tr ng y. Nh a m u dng bi lm tan cc ch sng t y, ch a h ng sng khng nu t c, cam rng t u m th i lot v cc m n trng nh c khng tiu, cc m n nh t, v t lot nhi m trng, tai c m .

dy th n kinh trong b nh ci, cc v t thng, th p kh p. D u M u c tc d ng tiu sng, gi m au, st trng, c m mu. V se, lm sn da. d. L c i v i c. e. M dng ngoi lm lnh s o, nh t l tr b ng. trong i s ng h ng ngy(bn, gh , salon,...). g. R dng ch a vim chn rng.

c.D u M u dng tr gh , n m tc v cc b nh v da ni chung, ch a vim

f. V cy dng tr b nh au d dy v xu t huy t bn trong. G cy dng

SVTH: L Minh Vng

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2.1.6. Cc bi thu c dn gian s d ng m u [25]

t d c v a lm thnh 100 vin, ngy u ng 2 l n, m i l n 4 vin. bi. Ho c d u M u tr n v i vi, chng nng ln bi. c nh a th dng 120 g g ch nh s c u ng nhi u l n. n bi lin t c vo chn rng.

Bi 1: au d dy: B t v M u 20 g, b t Cam th o nam 14 g, b t Qu 1 g, M n nh t, gh , l : H t M u gi nh , thm vi, un si ngu i lm thu c Bi 2: Gi i c: Ho nh a vo n c, u ng nhi u l n th m a ra. N u khng Bi 3: Cam t u m, vim rng th i lot: Nh a M u tr n v i b t Hong Bi 4: Rng ch y mu hay l i rng t t xu ng, chn rng l ra: R M u

v r Cu k (Rau kh i) li u l ng b ng nhau, s c n c ng m nhi u l n. nh c: R M u 40 g s c u ng. 2.1.7. Thu hi v ch bi n

Bi 5: Phong th p au xng v th n h au lng ho c b thng au

v , s cho nhi u d u nh t. Nn thu t thng 10 n thng 2 nm sau. H t dng ti hay p l y d u. Nh a thu quanh nm, phi kh, tn b t. R , l thu hi quanh nm, phi kh.
Qu m u c thu ho ch d ng chn ti, lc ny qu m u khng ch a d u.

Thu hi qu t t nh t vo lc cy c 7 10 nm tu i, qu chn r ng r i kh

Sau , chng c v nt cho n khi l p v b n t ra m t t. Ti p theo, x p nh ng qu

m u c v nt thnh m t l p r i em i phi kh ngoi n ng. Trong qu trnh h t kh c mu nu, v c mi thm, lc ny l ng d u c tng ln ng k . Th i gian di. Theo th ng k, trung bnh t m t cy m u c th tinh ch ra 11,7 kg d u, v 4680 kg d u/ha.

phi kh, h t m u b gi m tr ng l ng (t 7 g h t ti xu ng cn 4 5 g h t kh) v gian phi kh kho ng hai thng. Lc ny h t m u c th c d tr trong m t th i

SVTH: L Minh Vng

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CBHD: Th M Linh

2.1.8. Hnh nh v cy m u

Hnh 1.1.4. Hoa m u [29]

Hnh 1.1.5. Cc cng nhn ang tch v tri m u l y nhn p d u [30]

Hnh 1.1.6. Chi t xu t tinh d u m u theo tiu chu n Organic x ng c a cng ty Chuyn Thin Nhin [30]
SVTH: L Minh Vng

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CBHD: Th M Linh

2.2. THNH PH N HA H C C A CY M U
2 .2.1. Thnh ph n ha h c c a l[9,14,16,18,19,20] Inophynone, Isoinophynone, Calophyllolide, Inophyllum B, Inophyllum C, Inophyllum P, Inophyllum G1, Canophyllol, Inophyllum G2,

Canophyllol acetate, Canophyllic acid, Amentoflavone, Apetalic acid, Isoapetalic acid, (+)- calanolide A, (-)- calanolide B, Soulattrolide , (+)- calanolide C, 2.2.2. Thnh ph n ha h c c a thn cy [17] 2.2.2.1. Thnh ph n ha h c c a li cy 1,5,6-trihydroxyxanthone, Jacareubin,

6-(3-methyl-2-butenyl)-1,5-dihydroxyxanthone, 6-desoxyjacareubin,

2-(3-methyl-2-butenyl)-1,3,5,6-tetrahydroxyxanthone, 1,7-dihydroxyxanthone, 1,5,6-trihydroxyxanthone,

1,6-dihydroxy-5-methoxyxanthone,
SVTH: L Minh Vng

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CBHD: Th M Linh

2-(3-methyl-2-butenyl)-1,3,5-trihyroxyxanthone, 2.2.2.2. Thnh ph n ha h c c a g cy (timber) 6-(3-methyl-2-butenyl)-1,5-dihyroxyxanthone, 6-desoxyjacareubin, Jacareubin, 1,7-dihydroxy-3,6-dimethoxyxanthone, 2.2.2.3. Thnh ph n ha h c c a v cy Friedelin, Friedelan-3-ol, -amyrin, Sitosterol,

1-hydroxy-3,6,7-trimethoxyxanthone, 2.2.3. Thnh ph n ha h c c a v r T v r cy thu c: Inoxanthone, Frielan-3-one,

1,7-dihydroxy-3,6-dimethoxyxanthone,
[21]

Macluraxanthone, Brasiliensic acid, Inophyllolidic acid,

Caloxanthone B,

1,5 dihydroxyxanthone,

SVTH: L Minh Vng

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2.2.4. Thnh ph n ha h c c a d u th [2,9,10]

u, bao g m nhi u ch t khc nhau nh:

Nhn h t ch a 50,2% - 73% d u, d u m u c tch chi t t qu v h t m

d ng terpenoid.

2.2.4.1. Friedelin: C tn l canophyllal, canophyllol, canophyllic acid. y l

H3C CH3 H O H
CH3

CH3

H CH3

CH3

CH3 CH3 Friedelin

2.2.4.2.

a) Calophyllolide l m t phn t ch a lactonic v nhm methoxyl.

Cc d n xu t c a coumarin

Ph

MeO

Calophyllolide

c) Nhm Inophyllolid
SVTH: L Minh Vng

b) Calophyllic acid ( C25H24O6 )

11

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O OH

O OH

O R

O OH

Inophyllum G-1

Inophyllum G-2

Inophyllum P

2.2.4.3. Nhm Xanthone: Dehydrocycloguanindin, calophyllin-B, caloxanthone-A, caloxanthone-B, caloxanthone-C

O OH

jacareubin v 6-deoxy jacareubin, mesuazanthone-A, mesuazanthone-B,

OH

O O
Dehyrocycloguanindin

O OH
Calophyllin-B

OH

OH

HO

O OH
Jacareubin

O OH
6-desoxyjacareubin

SVTH: L Minh Vng

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OCH3 HO O

OH

HO

OH

OH

Caloxanthone A

Caloxanthone B

OH O O

O HO O

OH

OH

O
Euxanthone

Caloxanthone C

OH

OH

O OH
Mesuaxanthone A

OH OH

OH

Mesuaxanthone B

SVTH: L Minh Vng

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CBHD: Th M Linh

2.2.4.4.

Cc acid bo, glycerides, sterols v ba nhm lipid Ba nhm lipid chnh

B ng 2.1. Ba nhm lipid chnh c trong d u m u.

Neutral lipid Glycolipid

% kh i l ng 6,4% 92%

Phospholipid

Trong

1,6%

Monoacylglycerol

Neutral lipid

sn 1,3 Diaglyceride Free fatty acid

sn 1,2 (2,3) - Diaglyceride Triacylglycerol

2,4%

1,8% 2,6%

Sterols, sterolesters and hydrocarbon Monogalactosyldiacylglycerol Acylated sterolglucoside Monogalactosylmonoacylglycerol Phospholipid Glycolipid

82,3% 3,5%

7,4%

11,4% 22,2%

13,1%

Acylmonogalactosyldiacylglycerol Phosphatidylethanolamine Phosphatidylcholine Phosphatidic acid Phosphatidylserine

53,3%

46,3% 8,1% 6,1%

33,8%

Lysophosphatidylcholine

5,7%

B ng 2.2. Cc thnh ph n chnh c trong cc acid bo

SVTH: L Minh Vng

d u m u
14

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CBHD: Th M Linh

Oleic acid (C18:1)

Thnh ph n chnh trong cc acid bo (%)

Linoleic acid (C18:2) Stearic acid (C18) Palmitic acid (C16)

21,3%

49,4% 14,7%

Eicosanoic acid (C20)

12,66% 0,72% 0,94%

Eicosenoic acid (C20:1) Linolenic acid (C18:3)

0,28%

2.2.4.5. Ngoi ra, d u m u cn ch a cc tnh ch t terpenic, benzoic, v oxibenzoic acid, m t ph n nh vitamin F

2.3. TNH CH T V T L V HA H C C A D U M U [2]

B ngoi: T n t i Mi hng: C mi thm gi ng nh qu h ch. tan trong n c. d ng l ng, d u th c mu xanh m.

Tnh ha tan: C kh nng ha tan trong c n v cc lo i d u khc, khng Ch s khc x : 1,471 1,495 20C.

T tr ng: 0,910 0,960 Ch s acid : 10. Ch s Iod: 80 100.

20C.

Th i h n s d ng: 6 9 thng.

Ch s x phng ha: 185 235.

SVTH: L Minh Vng

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CBHD: Th M Linh

2.4. TC D NG C A CC CH T C TRONG D U M U [2]

n m.

2.4.1. Cc d n xu t c a coumarin: C tc d ng khng vim, khng khu n v tr 2.4.2. Nhm Xanthone: Bao g m dehydrocycloguanandin, calophyllin-B,

jacareubin, mesuaxanthone-A, mesuaxanthone-B v euxanthonecungx c tc v t sng, v t tr y

d ng khng vim, ngoi ra n cn c tc d ng lm gi m ch ng pht ban, v t au, 2.4.3. Friedelin: Cng c tc d ng khng khu n v tr n m. Trong :

khng khu n Proteus mirabilis nguyn nhn gy ra b nh nhi m trng ng ru t, nhi m trng v t thng, nhi m trng mu v vim ph i. khng khu n: b) Canophyllol: Cng c so snh v i ampicillin v amoxicillin, c th

a) Canophyllic acid: C tc d ng gi ng v i ampicillin v amoxicillin, c th

Staphylococcus aureus nguyn nhn c a ch ng vim, mng m , p xe, Cornebacterium diptheriae nguyn nhn c a b nh b ch h u. trng mu, nhi m trng ng th i n c ti u. inh nh t, nhi m trng v t thng, nhi m trng mu v tim mng k t.

Klebsiella pneumonia nguyn nhn c a nhi m trng v t thng, nhi m c) Friedelin: Cng c so snh v i ampicillin v amoxicillin, c th khng

khu n:

S.aureus nguyn nhn c a b nh n m. v t thng, vim xoang.

Pseudallescheria boydii nguyn nhn c a b nh n m ha s ng, mng m Trichophyton schoenleinii nguyn nhn c a cc n t si trn da, da u,

2.4.4. Cc acid bo

trn mng, b nh hecpet m ng trn.

ch l lm gia tng s pht tri n cc nguyn bo s i nn lm tng sinh m h t v tc ng ln s ti t o l p th ng b.

SVTH: L Minh Vng

C tc d ng ti sinh m. C ch lm lnh v t thng c a cc acid bo ny

16

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CBHD: Th M Linh

2.5. TC D NG D C L C A D U M U [2,7,22,23,25,27,28]
2.5.1. c tnh Qua nhi u ti li u th hi n nay cha ch ng minh c d u m u c c tnh. D u m u c tnh ch t quan tr ng nh t l c kh nng ti sinh m nn da. V d nh tr cc

2.5.2. Tc d ng c a d u m u i v i c th

c ng d ng r ng ri, dng ch a lnh cc v t thng li n s o,

v t thng b cn trng c n, b b ng, cc v t c c, v t c t, v t m , tr m n, lm

ngn ng a HIV, gi m au dy th n kinh, gi m au v t nh c ch ng pht ban, 2.5.3. a) Trong y h c ng d ng c a d u m u

D u m u c tnh khng khu n, khng vim, ngn ng a khu n t c u, chn, ngn ng a

Ch a tr ch ng au c v au dy th n kinh. Ch a tr ch ng au c. D u m u cn c kh nng tr b nh i ng v b nh tr, tr b nh th n lot c t cung, chm b i nhi m,

kinh t a, b nh zona, b nh th p kh p, b nh h i, vim m o, tr mn v

b) Trong m ph m

D u m u c ph i tr n v i cc lo i th o d c v tinh d u khc

d ng vo cc s n ph m chm sc da v tr m n. Hi n nay, cc cng ty m

ng

ph m trn th gi i s d ng m t s tinh d u ph i tr n v i d u m u tinh d u o i hng, tinh d u hoa h ng, tinh d u hoa phong l , v m t s tinh d u khc.

thnh cc d ng dung d ch ho c d ng kem lm s n ph m chm sc da l:

vi khu n t m d u m u c tc d ng sinh h c trong i u tr b ng.

ng d ng s n ph m ln men c a Acetobacter xylinum lm mng cellulose

SVTH: L Minh Vng

17

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CBHD: Th M Linh

s d ng d u m u ph i tr n v i tinh d u trm c v ramasol lm lnh nhanh v t thng. ng d ng vo cc s n ph m tr b nh v y n n, b nh m n r p v m n tr ng

ng d ng tnh ch t lm li n s o c a d u m u, h i d c h c Vi t Nam

c.

2.6. GI TR KINH T C A D U M U

tnh th m th u qua da t t, c mi thm, lm sng da nn th ng c a vo cc thnh ph m d ng n c (lotion), kem, pommade v cc m ph m khc. Vi t Nam hi n nay, d u m u c ti m nng l n trn th tr ng cc s n ph m tr

D u m u c dng trong d c ph m v cc b nh l da v m ph m nh

b nh ngoi da l n trong k ngh m ph m. Trong tng lai, d u m u c th k t

h p v i vitamin E, aloes vera (cy l h i, t c nha am) t o nn cc s n ph m sn sc da. Hi n nay c nhi u cng ty s n xu t d u m u ng chai nh Active Botanicals, Port Villa, Pure World Botanicals,

SVTH: L Minh Vng

18

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CBHD: Th M Linh

3.1. C S

Chng 3: PHNG PHP CHI T XU T C A PHNG PHP CHI T

[1]

bi t, c l p v tinh ch cc c u t c trong h n h p thnh nh ng c u t ring. Qu trnh chi t g m m t s giai o n sau: Giai o n 1: Dung mi th m t ln b m t nguyn li u sau

Phng php l phng php thu l y m t hay nhi u ch t t h n h p tch

th m su vo bn trong t o ra dung d ch ch a cc ho t ch t. Sau dung mi cc khe vch tr ng.

ti p t c ha tan cc ch t trn b m t b ng cch y cc b t kh chi m y trong Giai o n 2: Giai o n ti p t c ha tan cc ho t ch t trong cc ng

mao d n c a nguyn li b b c kn nh vo dung mi th m su vo cc l p bn trong. Ta c th chi t ch t r n b ng ch t l ng ho c ch t l ng b ng ch t l ng.

sang ch t l ng (l dung mi). C th tng t c chuy n h ng b ng cch nghi n chi t nng lin t c v i dung mi l ch t bay hi trn b chi t Soxhlet.

Chi t ch t r n b ng ch t l ng: L lm tan ho t ch t c t ch t r n

nguyn tng b m t ti p xc tr c khi chi t khu y. Th ng ch t r n c Chi t l ng trong dung d ch (ph n l n l n c): L l c dung d ch

v i dung mi thch h p c kh nng ha tan ch t h u c hn l dung mi c.

3.2. YU C U C A DUNG MI KHI CHI T

k thu t khc ph thu c vo dung mi chi t. B i v y dung mi dng chi t c n th a cc i u ki n sau:

Ch t l ng c a h p ch t thu c cng v i hi u su t chi t v cc i u ki n

mi s l n, trong s n xu t d gy h a ho n khi thu h i dung mi. v khng b thay i tnh ch t khi s d ng l i. nhi t.

C nhi t si th p. Tuy nhin n u th p qu th t n th t dung Khng c tc d ng ha h c i v i cc ch t c trong nguyn li u n nhi t b c hi c a dung mi ph i th p kh i tiu hao nhi u

C nh t b khng lm gi m t c khu ch tn.

19

SVTH: L Minh Vng

Lu n vn t t nghi p

CBHD: Th M Linh

ch t, c bi t i v i n c ph i t ha tan.

C kh nng ha tan l n cc ho t ch t nhng r t b i v i t p Khng c t o thnh h n h p n v i khng kh, khng c c

nh ng t p ch t khng bay hi v khi bay hi khong c c n c mi l . i v i s n ph m v khng c h i i vi ng i s d ng. Ph i r ti n v d mua.

Ph i tinh khi t, khng c n mn thi t b . Khng gy mi l

3.3. CC PHNG PHP CHI T XU T

v cch chi t. Phng php chi t xu t bao g m c vi c ch n dung mi d ng c chi t M t phng php chi t xu t thch h p ch c th ho ch nh m t khi

bi t r thnh ph n ha h c c a cy. M t lo i h p ch t c ha tan khc nhau trong t ng lo i dung mi. V v y khng th c m t phng php chi t xu t chung p d ng cho t t c cc h p ch t trong cy.

r t quan tr ng trnh th y phn h p ch t, trnh cc ph n ng ph , cc ph n ng chuy n v . Trong cy th ng ch a m t s c u t d c xem nh nh ng ch t gy

L a ch n phng php trch ly c c cao trch th l cng vi c

c n tr trong qu trnh chi t xu t ho c tinh ch h p ch t nh cc di p l c t silicon cng nhi m vo dung d ch ly trch.

Polyphenol, i khi cc ch t dng bi trn d ng c th y tinh: Vaselin, C nhi u cch s d ng dung mi trch ly m u cy. Khi cho dung

mi chi t vo, dung mi s th m qua mng t bo c a cy, cc ho t ch t trong t

bo s ha tan vo trong dung mi. Khi xu t hi n m t qu trnh th m th u gi a dung d ch chi t thnh trong t bo v dung mi bn ngoi. Qu trnh th m th u ny k t thc khi c s cn b ng v n ng h p ch t c a dung d ch bn trong v bn ngoi thnh t bo. Nh v y, Qu trnh th m th u. Qu trnh ha tan. s chi t x y ra hai qu trnh:

thc.nguyn li u ph i c xay nh n m c thch h p dung mi c i u ki n

SVTH: L Minh Vng

Hai qu trnh ny c th c hi n lin t c cho n khi c s chi t k t

20

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CBHD: Th M Linh

ti p xc v i thnh t bo m t cch d dng, thc y qu trnh chi t xu t m t cch nhanh chng v nng cao hi u su t. 3.3.1. Chi t b ng phng php ng m ki t (Percolation)

d ng ph bi n nh t v khng i h i nhi u thao tc cng nh th i gian.

Phng php ng m ki t l m t trong nh ng phng trch ly c s

d i y bnh l m t van kha c i u ch nh v n t c c a dung mi ch y, khi ngm m u cy trong dung mi sau m t th i gian nh t nh.Dung mi ch y ra nh vo bnh khu y ng m ki t ny. c h ng trong m t erlen bn d i, trn cao c m t bnh lng ch a dung mi y l qu trnh chi t lin t c thay th b ng dung mi m i. Tuy v y

D ng c g m m t bnh ng m ki t hnh tr ng, b ng th y tinh,

m ng i ta khng th c hi n lin t c ma m u cy c ngm lin t c trong dung mi kho ng 12 gi , cho dung mi bo ha ch y ra r i thay th b ng dung mi m i v ti p t c qu trnh trch ly. kh o st s chi t xu t hon ton cha, ng i ta th ng theo di b ng cch l y dung d ch trch ly th v i cc thu c th c trung c a ho t ch t. 3.3.2. Chi t b ng phng php ngm d m(Maceration)

ki t, ch l ngm b t cy trong bnh ch a th y tinh ho c thp khng g c n p y. Rt dung mi ph l p b t cy, yn vo nguyn li u v ha tan cc ch t t nhin trong cy. C th gia tng hi u qu trong bnh c ra v rt dung mi m i vo.

Phng php ngm d m khng hi u qu g hn so v i phng php ng m nhi t phng, dung mi s th m

chi t xu t b ng cch khu y b t cy ho c dng my l c nh . Sau 24 gi , dung mi 3..3.3. Chi t b ng phng php ng m ki t ng c dng

d m. B t cy c cho vo bnh chi t khc nhau, v d c 3 bnh A, B, C b t cy

y l s k t h p gi a phng php ng m k t v i phng php ngm

c cho vo c ba bnh. Cho dung mi vo bnh A, ngm v l y ra dung d ch

A1. Dung d ch ny ring, cho dung mi m i vo bnh A, d ch chi t l y ra l n

sau g i l A2. L y d ch A2 dng lm dung mi cho bnh B. D ch chi t B1 ring,

21

SVTH: L Minh Vng

Lu n vn t t nghi p

CBHD: Th M Linh

sau cho dung mi m i vo bnh B c d ch B2, d ch chi t ny c lm dung mi ngm b t cy cho bnh ti p theo, c ti p t c nh v y cho n cc

dung mi cho bnh C. Nh v y, dung d ch chi t ra t bnh chi t tr c c lm bnh sau. y l phng php c ng d ng nhi u trong s n xu t l n. Phng phng php nh gi t m m kha cho ch y thnh dng sau khi ngm m t th i gian nh t nh. 3.3.4. Chi t b ng Soxhlet

php ny ch khc phng php ng m ki t l d ch chi t sau khi l y ra khng theo

ny c u i m l s d ng m t l ng t dung mi m v n c th chi t ki t c ho t ch t. S chi t xu t t ng, lin t c nn nhanh chng.

B d ng c Soxhlet c bn s n v i nhi u lo i kch c . Phng php

dng pipette ht vi gi t dung mi ang ch a trong bnh ch a m u cy, nh ln m t knh hay gi y l c, dung mi bay hi s l i v t c n. N u th y khng cn m t th i gian n a. v t n a ngha l vi c chi t xu t ki t, n u th y c v t th ti p t c chi t thm Nh c i m c a phng php ny l khng chi t xu t c m t l ng nhi t si c a

Mu n bi t vi c chi t xu t c n ki t cha, tho ph n ng ngng hi,

l n m u cy nn ch thch h p cho vi c nghin c u trong phng th nghi m. M t b t ti n n a trong su t qu trnh chi t xu t m u cy lun lun phn gi i ho c t o cc h p ch t Artefat. 3.3.5. Chi t b ng cch un hon lu dung mi nn nh ng h p ch t km b n nhi t nh Carotenoid c th b th y gi i,

hn. un hon lu trn b p cch th y

B t cy v dung mi c ch a trong m i bnh c u c g n ng sinh

gian c n thi t dung d ch c n chi t c l y ra v l c qua gi y l c. Dung mi m i c cho vo v ti p t c chi t t 3 n 4 l n n khi ki t.

nhi t si c a dung mi, sau m t th i

v i n c m phng php m dn gian s c thu c u ng v m t s ch t cng tan c trong n c, ng i ta th ng dng h n h p CH3OH H2O ho c C2H5OH H2O.

Hi m khi ng i ta un b t cy v i dung mi l n c, d r ng trch ly

SVTH: L Minh Vng

22

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CBHD: Th M Linh

3.3.6. Chi t b ng phng php li cu n hi n c

bay hi c trong cy. D ng c g m m t bnh c u l n cung c p hi n c, hi t b i m t ng sinh hn, ta thu c h p ch t tinh d u v n c.

y l phng php c bi t ly trch tinh d u v nhng h p ch t d

n c s c d n s c vo bnh ch a m u cy, hi n c ti p t c bay hi v ngng

SVTH: L Minh Vng

23

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CBHD: Th M Linh

4.1. S C K C T [4]

Chng 4: PHNG PHP S C K C T

[1]

nh i trong cc ng hnh tr g i l c t. Ty theo tnh ch t c a ch t c s ph ), c ch phn b (c t phn b ), trao i ion (c t trao i ion),... t i ch trnh by s c k c t h p ph . 4.1.1 Nguyn t c

Trong s c k c t, ch t h p ph ho c ch t lm nn cho pha c nh c

d ng lm c t m s tch trong c t s x y ra ch y u theo c ch h p ph (c t h p

y chng

ct v i ch t h p ph ng vai tr pha tnh, dung mi r a c t l pha ng ch y qua ch t h p ph . i v i m i ch t ch t ring bi t trong h n h p c n tch, ty theo kh nng

S c k h p ph c ti n hnh trn m t c t th y tinh th ng ng g i l

h p ph v kh nng ha tan c a n i v i dung mi r a c t l y ra c l n l t tr c ho c sau. Ch t h p ph trong s c k c t th ng dng l oxyt nhm, silica gel,

CaCO3, than ho t tnh, polyamid,Cc ch t ny ph i c tiu chu n ha nh: - Al2O3 trung tnh (Merck), c h t 0.063 0.200 mm (70 200 mesh). ho t ha s I II 0.50% H2O 2.4% H2O 4.3% H2O

III V

IV

- Al2O3 baz, c h t 0.0063 0.200 mm (70 200 mesh) ho t ha s I II 1.2% H2O 3.5% H2O 5.8% H2O

15% H2O

6.6% H2O

III V

IV

- Silica gel 60 c h t 0.063 0.200 mm.

SVTH: L Minh Vng

10% H2O

8.1% H2O

24

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nhin.

Silica gel l pha tnh c s d ng r ng ri nh t tch cc h p ch t t Dung mi dng trong s c k c t c th t ng lo i ring bi t ho c l h n V i cc ch t h p ph c i n, dung mi s d ng c phn c c tng d n.

- Polyamid M K c h t < 0.07 mm.

h p 2, 3 lo i dung mi v i t l thch h p.

nt mi n i v i m t ph u ch a dung mi, lo i ny th ng bn s n trn th

C t l nh ng ng hnh tr b ng th y tinh, u d i c kha, u trn c

tr ng v i nhi u lo i kch c l n nh . Ho c c t cng c th t l p b ng m t ng th y tinh th ng, u d i nh n i v i m t ng cao su, dng m t kha kim lo i i u ch nh t c ch y c a dung mi.

knh nh v chi u di cng di th s tch cng t t. M t vi c t c kch th c bn s n tng ng v i chi u di v kch th c c t: ng knh (cm) 1 2 Chi u di (cm) 15 25

Vi c l a ch n kch th c c t r t quan tr ng. Thng th ng c t c ng

40

60

4.2. K THU T TRI N KHAI

4.2.1. Chu n b c t R a c t tht s ch, trng v i n c c t v s y kh.

m i i m trong c t thnh m t kh i ng nh t. -

K p c t th ng ng trn gi s t

Cho bng gn vo y c t (c th cho thm m t l p ct m n s ch).

Yu c u c a c t s c k l ch t r n dng lm c t ph i phn tn ng Cho ch t h p ph vo c t th ng g i l nh i c t.

SVTH: L Minh Vng

25

Lu n vn t t nghi p

CBHD: Th M Linh

T l =

Tr ng l ng ch t phn tch Tr ng l ng ch t h p ph

thng th ng t 1/20, 1/30, 1/50, 1/100, -

Ty thu c vo kh nng tch c a ch t h p ph m t l ny thay i

C hai cch nh i c t: nh i c t t v nh i c t kh.

nh silica gel, sephadex, th ph i ngm trong dung mi m t th i gian tr c khi cho vo c t trnh b n t c t. L c, tr n u b t h p ph v i dung mi t o thnh

Nh i c t t: Dng cho cc ch t h p ph c kh nng trng phnh

m t h n d ch, rt vo c t, ch t h p ph s l ng t nhin xu ng y c t. H n d ch cng khng c qu l ng ph i rt nhi u l n vo c t. Ch trong qu trnh dung mi trong c t. Sau khi nh i c t h t ch t h p ph vo c t dng dung mi h ng c ti p t c rt vo c t v cho ch y lin t c m t th i gian c t h p ph ta cho thm m t l p ct ho c bng khng lm xo tr n m t gel. n nh Al2O3, CaCO3. Ch t h p ph c nh i t t vo c t -

dung mi v ch t h p ph khng nn qu s t khi n b t kh b gi trong c t v nh i c t, dung mi v n lin t c ch y u ra c t h ng, v khng c kh

c hon ton n ton n nh. M t thong trn u c t ph i n m ngang, ng i Nh i c t kh: Dng cho cc ch t h p ph khng c kh nng trng

ph u c cu ng di. Dng m t que b ng g ho c cao su g nh v u chung quanh c t theo chi u t d i ln b t xu ng u n. Khi ch t h p ph c c n nh v t lc ny tr i, khng c kh dung mi trong c t. 4.2.2. a ch t phn tch vo c t

d ng kh b i m t

cho h t vo c t m i rt dung mi vo v cho ch y lin t c m t th i gian c t

thnh m t l p m ng ng u trn m t c t b ng ph ng. C nhi u phng php a ch t phn tch vo c t. Phng php dng a gi y:

Yu c u c a vi c a ch t phn tch vo c t l ph i phn tn ch t th

trong c a c t kho ng 0.5 mm. Dng kim chm thnh nh ng l th ng cch u gi y th m u dung d ch m c. L y gi y ra b c hi dung mi b ng cch
SVTH: L Minh Vng

Dng gi y l c c t thnh m t a trn c ng knh nh hn ng knh

nhau. Ch t c n phn tch c ha tan trong m t l ng dung mi v a , cho

26

Lu n vn t t nghi p

CBHD: Th M Linh

s y, r i ti p t c t m dung d ch thu c th . N u ti n hnh v i c t l n, l ng ch t th nhi u, c th dng nhi u a gi y. Sau khi c t c n nh v i dung mi, m vi cho dung mi ch y cho

n khi m c dung mi b ng v i m t ngang ch t h p ph th kha vi l i. t c n m t l p ct m n ln gi y v b t u cho dung mi ch y. Cho th ng dung d ch th ln c t:

th n cc a gi y ln m t c t, dng ng ht cho dung mi t m t u gi y, cho

nhng ph i b o m ha tan hon ton). Dung d ch th c n ng cng m c m i n m thnh m t l p m ng trn u c t. C t n nh, m vi cho dung mi ch y cho n khi m t c t h p ph v a kh th ng l i. Dng ng ht cho dung (khng c ch t h p ph

Ha tan ch t phn tch vo m t l ng v a dung mi (cng t cng t t

d ch th ch y d c thnh c t. M kha bn d i cho dung d ch th ng m vo c t ng m h t vo c t, dng ng ht l y m t t dung mi r a thnh c t v cng cho ng m h t vo c t. Ti p t c cho dung mi b t u qu trnh gi i ly. Tr n ch t th v i m t l ng ch t h p ph : u c t b kh). Khi ton b l p dung d ch th

u, s y kh r i cho vo c t b ng cch r i thnh m t l p u n trn m t c t. c , nhng ph i b o m cc yu c u k thu t sau: Ch t th ha tan hon ton.

Tr n dung d ch ch t phn tch v i m t l ng nh ch t h p ph cho th t Trong ba cch trn, cch cho th ng dung d ch vo c t l g n v nhanh hn

ng m vo c t t o thnh nh ng l p c b dy u nhau l ch ng t k thu t m b o. 4.2.3. R a c t - cn c g i l gi i ly ch t ra kh i c t

Dung d ch ch t th ph i n p vo c t u.

Cho dung mi nh nhng, khng lm xo ng m t c t. N u ch t th

Khi ton b ch t th ng m h t vo c t, m i cho ti p dung mi m i.

th ti n hnh gi i ly c t b ng p su t th ng ho c p su t nn.

Ty theo ch t h p ph dng v yu c u t c ch y c a c t m ng i ta c

SVTH: L Minh Vng

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l c. C t p su t th ng c nh c i m l ch y ch m, ch dng cho cc ch t h p ph c kch th c h t l n. R a c t b ng p su t nn: Ng i ta th ng cho m t dng kh nn (kh

R a c t b ng p su t th ng: Ngha l dung mi ch y ra nh vo tr ng

nitrogen ho c khng kh) vo u c t. T c dng kh c th c ki m sot nh vo m t van i u ch nh. C t dng p su t nn ph i c nt b o m kn mi ng, v c kha ho c dy bu c ch t vo mi ng c t.

d ng kch th c h t gel lm pha tnh v vi c s d ng p l c gi i ly dung mi ra kh i c t. M t h p ch t c th b ch t h p ph gi l i m nh hay y u cn ty thu c s c k c t c i n, dung mi r a c t c dng v i phn c c tng

Vi c l a ch n cc phng php r a c t khc nhau ty thu c vo vi c s

vo phn c c c a dung mi gi i ly.

d n. Dung mi ph i tinh khi t, v nh ng t p ch t l n vo dung mi th ng lm khi s d ng.

thay i phn c c c a dung mi , v th ng i ta th ng c t dung mi tr c Hi n nay trn th tr ng c bn lo i silica gel o pha. Khi s d ng silica

gel ny lm pha tnh, th pha tnh c tnh h p thu t l v i tnh than d u c a h p dung mi c ch a n c. Nh v y cc thnh ph n phn c c trong h n h p ch t

ch t c s c k, cho nn pha ng s d ng th ng l n c ho c cc h n h p c n s c k s c gi i ly ra kh i c t tr c, cn cc ch t khng phn c c s ra sau. Phng php ny c ng d ng r t c hi u qu i v i cc h p ch t phn c c m nh trong th c v t nh saponin, triterpen. cch pha t l tng d n ho c gi m d n.

S thay i t dung mi ny sang dung mi khc ph i chuy n t t b ng

SVTH: L Minh Vng

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Chng 5:

QUY TRNH C L P CC CH T T TRI M U

H T

5.1. QUY TRNH THAM KH O 1

H t nhn 210 g

Chi t 2 l n v i ethanol (850x2 ml) C quay

Thu ch t mu nu 79 g Pha long v i 500 mL H2O Thm ti p 1 l ng EtOAc

Cao EtOAc 15 g

Ph n tan trong EtOAc C quay p su t th p

Ph n tan trong n c

S c k c t dung 400 g silica gel H dung mi n-hexane/EtOAc 10:1; 7:1; 5:1; 4:1; 3:1; 2:1)

Thu 9 phn o n

Phn o n I (1,85 g)

Phn o n III (4,7 g)

Phn o n V (2,06 g)

Phn o n VII (2,24g)

Phn o n IX

SVTH: L Minh Vng

Phn o n II(836 mg)

Phn o n IV(1 g)

Phn o n VI (2,65g)

Phn o n VIII(1,41 g)

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Phn o n S c k c t v i 60 g silica gel. H dung mi (nhexane/CHCl3/MeO H 150:150:1 50:50:1 20:20:1 10:10:1 5:5:1)

Phn o n S c k c tv i 50g silica gel H dung mi (hexane/a cetone 100:1 50:1 25:1 10:1 7:1 5:1

Phn o n VII S c k c t v i 35 g silica gel. H dung mi (nhexane/CHCl3/ MeOH 150:150:1 50:50:1 20:20:1 15:15:1) Inophylin A

Inophylin B (570 mg)

Phn o n A

Phn o n B

Phn o n C

Inocalophyllin A methyl ester

Inocalophyllin B methyl ester

Calophyllolide (2,7mg)

C cng th c c u t o:

Ph

O O

OH

COOMe

O O

OH

COOMe

M eO

In o c a lo p h y llin A m e th y l e s te r

In o c a lo p h y llin A m e th y l e s te r

C a lo p h y llo lid e

SVTH: L Minh Vng

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5.1. QUY TRNH THAM KH O 2[21]

H t nhn 850 g Chi t v i CH2Cl2-MeOH (1:1) trong 24 gi

D u mu vng 250 g L y 20 g d u trn em: - S c k c t silica gel ( 230-400 mesh,Merck) - H DM (n-hexaneEtOAc) - S c k TLC. Thu 117 l

P I L 1-10

P II L 11-18

P III L 19-37

P IV L 38-55

P V L 56-79

P VII L 80-117

SVTH: L Minh Vng

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P II 43,4 g

-S c k c t silica gel. - H D/M (n-hexane-EtOAc) - S c k TLC. Thu c 110 l

19-20

65-76

77-87

Hexane/EtOAc (19:1)

Hexane/EtOAc (9:1)

Hexane/EtOAc (17:3)

Calophyllolide 800 mg

Calaustralin 300 mg

Inphyllum E 300 mg

C cng th c c u t o:
Ph

Ph

MeO

O O

SVTH: L Minh Vng

Calophyllolide

Inophyllum E

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5.3. QUY TRNH THAM KH O 3[3]

NH A ( 1 kg) + dd NaHCO3, kh y u tch l p. + Tch ring ph n u D CH KI M + NaCl bo ha n khi tch l p l ng m t ngy. Tch b k t t a.

D CH KI M

D CH BENZEN

+dd HCl 10% v i 10 mLx3 + L c v i benzen (5 l n 300 mL)

R a n c t i trung tnh C quay thu h i dung mi(t=60oC)

C N COUMARIN TP(P=156 g)

SVTH: L Minh Vng

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C N COUMARIN 70 g + S c k c t p su t gi m phn l p coumarin. + C t 5,5x15 cm, 180 g silica gel 60H. + Dm: n-hexane, cyclohexane, benzene, ethyl acetate v methanol + Dng SKLM ki m tra

Phn o n A

Phn o n B

Phn o n C

Phn o n D, E, F,..

Calophyllolide

Ph

MeO

Calophyllolide

SVTH: L Minh Vng

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CBHD: Th M Linh

TH C NGHI M

PH N II

SVTH: L Minh Vng

35

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Chng 1: PHNG TI N V PHNG PHP 1.1. PHNG TI N

NGHIN C U

cho qu trnh ly trich v chay c t s c k.

Cc d ng c nh bnh tam gic, chai ng d ng d ch, chai bi c s d ng

v thu h i dung mi d i p su t th p nh m thu cc cao c a m u dung d ch trong qu trnh chi t l ng l ng ho c gi i ly c t s c k. C t 1: ng knh 4 cm. C t 2: ng knh 3cm. Cc dung mi dng tch g m: Ethanol, benzen. B ng m ng ch y s c k (Merck). Di 40 cm. Di 60 cm. C t s c k g m 3 c t c kch th c khc nhau:

My c quay: L m t d ng c r t quan tr ng, dng c c n dung d ch trch

Ha ch t dng nh i c t s c k: Silica gel G 60 (Merck). Ngoi ra cn dng cc ha ch t khc nh: H2SO4, hi Iod, Methanol.

1.2. PHNG PHP NGHIN C U

1.2.1. Phng php tch chi t D a vo nguyn t c coumarin tan trong n c khi m vng lacton mi

tr ng ki m, v tan trong dung mi h u c km phn c c khi ng vng lacton trong mi tr ng acid chi t xu t coumarin t d u th. 1.2.2. Phn l p cc c u t h u c Dng k thu t s c k c t c i n

SVTH: L Minh Vng

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1.2.3. nh tnh

(Merck), dy 0,200 mm. H dung mi khai tri n benzen ethyl acetate (9:1), petroleum ether - ethyl acetate (2:1), n-hexane - ethyl acetate (2:1) pht hi n v t d i n UV, ph n ng hi Iod ho c phun thu c th H2SO4 trong methanol. 1.2.4. Xc nh c u trc Phng php v t l: o i m nng ch y.

S c k l p m ng c th c hi n trn b n trng s n silica gel F 254

Phng php ph nghi m:UV, IR, NMR, MS

SVTH: L Minh Vng

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1.2.5. Quy trnh th c nghi m chi t tch v c l p cc h p ch t h u c

Theo ti li u cng b

c a nh a t d u m u

ch n quy trnh c l p nh sau:

D U TH (300 gam)

[3,6,21]

v i u ki n c a phng th nghi m chng ti

Chi t v i c n tuy t i 100 mL x 6 L y ph n tan trong c n

NH A (62,7 gam)

+ dd NaOH 10% v i 10 mL x 3 kh y u tch l p

D CH KI M 1 + NaCl bo ha n khi tch l p l ng m t ngy. Tch b k t t a.

D CH KI M 2

D CH BENZEN

+dd HCl 10% v i 10 mLx3 + L c v i benzen 100 mLx7

C qua y thu h i dung mi

Cao BENZENE TP(8,77 g)

SVTH: L Minh Vng

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Cao Benzene TP ( 8,77 gam) + S c k c t v i 200 gam silica gel G 60 (Merck). +H dung mi gi i ly tng d n phn c c: n-hexane/ethyl acetate (20:1 n 0:1)

Phn o n A L 1-20 Phn o n B L 21-32

Phn o n C L 33-54 Phn o n D L 55-63

Phn o n E L 64-75 Phn o n F L 76-91

Phn o n G L 92-98

SVTH: L Minh Vng

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Phn o n C (0,90 g)

- S c k c t v i 50 g silica gel G (Merck) - H dung mi gi i ly: - PE/EtOAc (2:1)

Phn o n I L 1- 30

Phn o n II L 31- 52

Phn o n III L 53 - 72

Ch t A (0,36 g)

SVTH: L Minh Vng

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Chng 2: TH C NGHI M
2.1. I U CH NH A T
D u th c c p t i tr ng i h c Y D c TP. H Ch Minh. L y 300 gam d u th cho vo bnh chi t 500 mL, chi t l ng l ng v i ethanol 100 mLx 6. quay l i v i p su t th p Hi u su t: 600 C thu c 62,7 gam cao th c mu vng m. Tch b ph n n m d i c a bnh lng, l y ph n trn. D ch chi t ny c c

D U TH

H% =

62.7 100 = 20,9% 300

2.2. NH TNH CAO ETHNOL S B M NG

B NG S C K B NG

T cao ethanol thu c t qu trnh trn chung t b c u ti n hnh nh tnh s b thnh ph n ha h c c a cao ethanol tr c khi ti n hnh tch coumarin b ng s c k b n m ng v i h dung mi gi i ly l n hexane/EtOAc (9:1). Thu c th hnh l dng hi Iod.

Hnh 2.1 S c k b ng m ng cao ethanol v i h gi i ly Benzene/EtOAc (9:1).

2.3. QU TRNH I U CH COUMARIN T

tr ng ki m, v tan trong dung mi h u c km phn c c khi ng vng lacton trnh chi t c ti n hnh nh sau:
SVTH: L Minh Vng

D a vo nguyn t c coumarin tan trong n c khi m vng lacton

CAO ETHANOL

mi

trong mi tr ng acid chi t xu t coumarin t cao trch t cao ethanol. Qu

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B c 1:

bnh chi t 30 mL dung d ch NaOH (10%) m i l n 10 mL quan st kh nng tan trong dung d ch ki m gi ti n hnh th nghi m ti p theo(g i l dung d ch ki m 1). B c 2:

Cho 62,7 gam cao ethanol cho vo bnh chi t lo i 500 mL sau cho vo

tch l p, lc ny dung d ch chuy n t mu vng sang mu tr ng s a. L y ph n

ha sau l ng m t ngy. Qu trnh k t t a

Dung d ch ki m 1 cho vo c c 500 mL, sau cho ti p 15 mL NaCl bo xy ra ch m nn c n i 24 gi

c k t t a mu tr ng xanh (g i l ph n nh a), r i tch b k t t a. Ph n cn l i ki m 2).

sau khi tch k t t a c gi l i lm th nghi m ti p theo (g i l dung d ch B c 3:

ny 30 mL dung d ch HCl 10%. Sau , cho vo bnh lng 500 mL sau chi t l ng l ng v i benzen 7 l n m i l n 100 mL. L y ph n tan trong dung mi ben benzen vng ti. Hi u su t: zen ( dung d ch mu vng), sau c quay p su t th p 600 thu c 8,77 cao

Dung d ch ki m 2 cho vo c c 500 mL, sau cho thm vo dung d ch

H% =

8,77 100 = 13,99% 62,7

SVTH: L Minh Vng

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Cao Ethanol (62,7 gam)

+ dd NaOH 10% v i 10 mL x 3 kh y u tch l p

D ch ki m 1 + NaCl bo ha n khi tch l p l ng m t ngy. Tch b k t t a.

D ch ki m 2

D ch Benzene

+ dd HCl 10% v i 10 mLx3 + L c v i benzen 100 mLx7

C quay thu h i dung mi Cao Benzene TP(8,77 g)

2.4. S C K C T L N M T CAO BENZENE

m t phn o n, c quay thu h i dung mi.

qu trnh gi i ly b ng s c k b ng m ng g p cc l c Rf gi ng nhau thnh C t s c k di 60 cm, ng knh 4 cm. Dung mi n p vo c t l n-hexene.

Th c hi n s c k c t chia cao benzene thnh cc phn o n, theo di

Ch t h p ph n p vo c t l silica gel 60H Merck. Cch nh i c t: p d ng phng php nh i t, cn kho ng 150 gam silica

gel r i cho t t l ng nh silica gel vo trong bnh tam gic 250 mL ch a m t m t th i gian kho ng 15 pht. Sau n p vo c t. C ti p t c nh th cho n khi n p xong. Ch t phn tch: L y cao benzene c n p d i d ng dung d ch vo c t Dung mi gi i ly: n-hexane/EtOAc tng d n m c phn c c t (20:1
43

l ng dung mi n-hexane, kh y u trnh vn c c l i. silica gel trng n

(ch r ng nn n p t t vo c t nn trnh xo tr n b m t c t). n 0:1).

SVTH: L Minh Vng

Lu n vn t t nghi p

CBHD: Th M Linh

thnh m t phn o n.

hi Iod, nh ng l no c v t s c k gi ng nhau v Rf g n b ng nhau th g p l i

H ng m i l 100 mL sau s c k b ng m ng . Thu c th hi n hnh l

Hnh 2.2. S c k b ng m ng cao benzene v i h dung mi gi i ly Benzene/EtOAc (9:1)

Hnh 2.3. S c k c t cao benzene

SVTH: L Minh Vng

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B ng 2.1. K t qu s c k c t cao benzene Dung mi gi i hexane/EtOAc 20 : 0 ly c t nKh i cao

Phn o n

S TT l

l ng (gam) 0.25

D ng v t SKLM

D ng ch t

Ghi ch

1- 20

V t di

vng hi xanh Mu

Mu

kh o st Khng Kh o

Khng

B C D E F G

21 32 33 54 55 -63 64 - 75 76 - 91 92 - 98

19 : 1 17 : 1 15 : 1 10 : 1 5:1 3:1

2.01 0.90 0.25 0.43 0.27 0.34

V t di V t trn V t hi V t hi V t trn V t trn m m di trn g n

vang hi Mu Mu xanh

kh o st st ti p kh o st kh o st kh o st kh o st Khng Khng Khng Khng

vng vng

Mu hi xanh Mu

xanh xanh Mu

2.5. S C K C T L N 2 PHN O N C

m t phn o n, c quay thu h i dung mi.

qu trnh gi i ly b ng s c k b ng m ng g p cc l c Rf gi ng nhau thnh C t s c k di 40 cm, ng knh 3 cm.

Th c hi n s c k c t chia phn o n C thnh cc phn o n, theo di

Ch t h p ph n p vo c t l silica gel 60H Merck.

Dung mi n p vo c t l Petrolium ether / ethyl acetate(3:1).

SVTH: L Minh Vng

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gel r i cho t t l ng nh silica gel vo trong bnh tam gic 250 mL ch a m t l ng dung mi PE/EtOAc (3:1), kh y u trnh vn c c l i. silica gel trng n m t th i gian kho ng 15 pht. Sau n p vo c t. C ti p t c nh th cho n khi n p xong.

Cch nh i c t: p d ng phng php nh i t, cn kho ng 50 gam silica

(ch r ng nn n p t t vo c t nn trnh xo tr n b m t c t. n 0:1).

Ch t phn tch: L y phn o n C c n p d i d ng dung d ch vo c t Dung mi gi i ly: PE/EtOAc tng d n m c phn c c tng d n t (3:1

m t phn o n.

Iod, nh ng l no c v t s c k gi ng nhau v Rf g n b ng nhau th g p l i thnh

H ng m i l 10 mL sau s c k b ng m ng. Thu c th hi n hnh l hi

Hnh 2.4. S c k c t phn o n C

Hnh 2.5.SKLM phn o n C h Benzene/EtOAc(9:1)

SVTH: L Minh Vng

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B ng 2.1. K t qu s c k c t phn o n C Dung mi PE/EtOAc 3 :1 gi i ly c t Kh i cao

Phn o n I

S TT l

l ng (gam) 0.009

D ng v t SKLM

D ng ch t

Ghi ch Khng

1- 30

V t trn nh t

Mu hi Mu hi vng

kh o st Kh o st ti p

II

31 52

2: 1

0.036

V t trn m

tr ng xanh vng Mu

III

53 72

1:1

0.700

V t di

kh o st

Khng

2.6. QU TRNH K T TINH V LM S CH mu tr ng hi vng. 48 gi A.

Phn o n II g p l i, sau c quay thu dung mi ta c 0,036 gam ch t nhi t phng sau xu t hi n tinh th mu

tr ng hi vng. Sau r a tinh th v i v i acetone/ethanol (1:1) 3 l n, g i l ch t Sau ch m b ng m ng v i 3 h dung mi khc nhau xem m c

tinh khi t c a ch t.

SVTH: L Minh Vng

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n-hexane/EtOAc(2:1)

Hnh 2.5 H dung mi

Pet. Ether/EtOAc(2:1)

Hnh 2. 6H dung mi

Hnh 2.7 H dung mi BENZENE/EtOAC(2:1)

Hnh2.8 S c k l p m ng ch t A v i 3 h dung mi nh trn. .

SVTH: L Minh Vng

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CBHD: Th M Linh

K T QU

PH N III

V TH O LU N

SVTH: L Minh Vng

49

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KH O ST CH T THU C SAU QU TRNH C L P

3.1. PHNG PHP
trc c a ch t m chng ti c l p c. Trong qu trnh th c hi n chng ti s d ng: Sau khi c l p h p ch t A b ng s c k c t, chng ti ti n hnh kh o st c u

Xc nh i m nng ch y b ng my Stuart Scientific (SMP3) t i phng h u c b mn Ha H c Khoa Khoa H c. Minh. Ch y ph IR xc nh nhm ch c t i vi n Ha H c, Thnh Ph H Ch

3.2. K T QU
- i m nng ch y l 1530C.

H p ch t

So snh v i ti cng b 1530C

3:

H p ch t A

i m ch y

Calophyllolide -

1580C - 1600C

S c k b n m ng : Cho m t v t trn mu vng.

f1

2,4 = 0,48 (H : n-hexane/EtOAc(2:1) 5

R
R

= f2
=

f3

3,6 = 0,72 (H : Bezene/EtOAc(2:1) 5

2,5 = 0,5 (H : PE/EtOAc(2:1) 5

SVTH: L Minh Vng

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K t qu o ph IR v snh v i cc ti li u cng b B ng3.1 K t qu o ph IR: Ph IR

(cm-1)

3286,56 2836,54 1672,42 1656,11 1305,55 1193,21 1171,16 997,43 889,08 805,16 600,90

CH3

Nhm ch c

Vng thm ceton ceton

anken anken CH thm c nh nhau

CH thm c nh nhau CH thm c nh nhau CH thm c nh nhau

B ng 3.2 K t qu o ph IR h p ch t Calophylloid cng b : Ph IR

2968 1728 1662 1639 1579 1496 1380 1334 1276

(cm-1)

Vng thm Lacton ceton ceton ceton anken anken anken

Nhm ch c
O Ph

MeO

Calophyllolide

SVTH: L Minh Vng

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r ng ch t A m chng ti c l p c c nhi t nng ch y g n kho ng nhi t v i k t qu c a Calophyllolide cng b

3.

Qua cc k t q a o nhi t nng ch y, k t qu o ph c th k t lu n s b

nng ch y c a Calophyllolide. V o ph ch t A c cc nhm ch c g n gi ng

SVTH: L Minh Vng

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K T LU N V KI N NGH

PH N IV

SVTH: L Minh Vng

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4.1.K T LU N

Trong th i gian lm th nghi m chng ti th y mnh cn nhi u v n ph i h c h i

Qu trnh lm th nghi m gip chng ti n m v ng hn nh ng ki n th c h c.

thm. Th c nghi m c l p c h p ch t A, nhng chng ti ch m i kh o st nhi t nng ch y, v o IR xc s b nhm ch c c a ch t A. V chng ti cng ti n c nhi u thng s g n gi ng. Nhng v n cha i u ki n xc nh ch t A l Calophyllolide. hnh so snh v i cc ti li u cng b v Calophyllolide[3], chng ti nh n th y r ng

4.2.KI N NGH

nh ng s li u cha xc nh c c u trc c a ch t A c l p v cng nh d c tnh. Chng ti c m t s ki n ngh sau: o thm ph UV, MS, NMR xc nh r thm c u trc c a ch t A. Ki m tra ho t tnh sinh h c c a ch t A. thnh r thm ph n ha h c c a nh a. Nghin c u, c l p thm cc ch t trong nh a t h t nhn xc nh Nghin c u thm tc d ng d c l c a d u th, d u tinh v nh a.

Qua th i gian th c hi n chng ti t nh ng k t qu nh trn. Nhng v i

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L C

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