Hp cht thin nhin

BI TP HP CHT THIN NHIN

Cu 1: Tm hiu v s sinh tng hp Terpenoid? Tr li: Hin nay, ngi ta xc nh tin cht ca monoterpen l pirophosphat isopentenil (IPP). Cc IPP ny c sinh tng hp t acid mevalonic. Acid mevalonic c to thnh t acid acetic trong cc m sinh vt. C ch to ra acid mevalonic c thc hin nh sau:

2CH3CO SCoA Acetil CoA

CH3COCH2CO SCoA + CoA SH Acetoacetil CoA CH3CO SCoA

CH2 COOH CH3 C CH2 CH SCoA OH OH NADPH CH2 COOH CH3 C CH2 CH2 OH OH Acid mevalonic

NADPH

CH2 COOH CH3 C CH2 CO SCoA + CoA SH OH

Acid mevalonic lc ny c chuyn ha thnh acid 5-pirophosphatmevalonic theo s sau:

CH2 COOH CH3 C CH2 CH2 OH OH Acid mevalonic

ATP

CH2 COOH CH3 C CH2 CH2 OP OH ATP CH2 COOH CH3 C CH2 CH2 OPP OH Acid 5-pirophosphatmevalonic

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Hp cht thin nhin

Bc bin i k tip ca acid 5-pirophosphatmevalonic l bc bin i c sc nht ca s bin dng isopren.

CH2 H 2C H2C C O H C

OPP OH CH3 O - H 2O - CO2 H2C CH2 OPP CH2 C CH3

Acid 5-pirophosphatmevalonic Sinh tng hp monoterpen

Pirophosphat isopentenil

Pirophosphat isopenenil (IPP) l n v cn bn trong qu trnh sinh tng hp monoterpen. S tham gia ca IPP vo cc qu trnh trn din ra nh sau:

CH2 OPP CH2 C H2C CH3 Isomeraz

CH2 OPP CH C H3C CH3

Pirophosphat isopenenil(IPP)

Pirophosphat dimetilalil(DMAPP)

OPP PPO H

OPP

IPP + DMAPP

Pirophosphat geranil(GPP)

Hu ht cc monoterpen c to thnh t GPP hoc t ng phn hnh hc ca n l pirophosphat neril (NPP), vi ni i nm cu hnh cis, irophospat neril l tin cht cho cc monoterpen chi hon.

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CH2OPP CH2OPP

GPP * S sinh tng hp monoterpen chi phng

NPP

CH2OPP

GPP

OH CH2OH

Geraniol

Linalol

Mircen

CHO

CHO

Citral

Citronelal

Ocimen

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* S sinh tng hp monoterpen n hon

OPP CH2 OPP

H GPP LPP Limonen

HO

Carvon

Carveol

* S sinh tng hp monoterpen nh hon

OPP

GPP

* *

* * * * *

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Hp cht thin nhin

Sinh tng hp sesquiterpen

OPP OPP H OPP

GPP

IPP

FPP

Pirophosphat farnesil (FPP) * S sinh tng hp sesquiterpen chi phng

Isomeraz
OPP Pirophosphat farnesil

OPP

Pirophosphat nerolidil

* Sinh tong hp sesquiterpen chi hoan Ty theo s ng vng ca cc cation dn xut t 2Z,6E-FPP hoc 2E,6E-FPP to nn sn c bn ca cc hp cht sesquiterpen chi hon (mt, hai hay ba vng). Cc kiu ng vng ca cc cation ny xy ra theo cc kiu to ni nh sau:

2Z,6E-FPP

2E,6E-FPP

Th d trong s ng vng vi cation dn xut t 2Z,6E-FPP cho sesquiterpen n hon vng 6:

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Hoc cho sesquiterpen nh hon sn azulen:

Hoc cho sesquiterpen nh hon sn naptalen, th d trong s sinh tng hp cadinen

H H

H H

Hoc cho sesquiterpen nh hon sn cariophilan, nh trong s sinh tng hp cariophilen.

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Hp cht thin nhin

Cariophilen

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Hp cht thin nhin

Cation dn xut t 2E,6E-FPP cng cho phn ng ng vng, th d nh s sinh tng hp germacren B (vng 10).

Germacren

Hoc trong s sinh tng hp humulen (vng 11).

Humulen

Trn nay, l s gii thiu mt s c ch sinh tng hp sesquiterpen kinh in, cn rt nhiu trng hp khc ang tip tc nghin cu. Cu 2: V v gi tn ng phn quang hc ca Linalool? Tr li:

Coriandrol (3S)-3,7-dimethylocta-1,6-dien-3-ol
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Licareol (3R)-3,7-dimethylocta-1,6-dien-3-ol 8

Hp cht thin nhin

Cu 3: Ti sao ngi ta khng dng acetone v diethyl eter lm dung mi gii ly trong sc k ct tch monoterpen? Tr li: Ngi ta khng dng diethyl ether v acetone l nhng dung mi d bay hi nhit thng nn khi ta s dng chng gii ly trong qu trnh sc k ct th rt hao ph, nu khng theo di cn thn th s dn n s nt ct, nh hng n qu trnh tch cc hp cht trn ct. Mt khc, do nhiu hp cht monoterpen v sesquiterpen c phn cc ln hn c hai dung mi trn, do trong qu trnh gii hp ph th diethyl ether v acetone khng li ko c cc hp cht ny ra khi ct sc k. V vy, ta cn chn nhng dung mi hoc h dung mi khc t bay hi v c phn cc cao hn sao cho vic tch cc monoterpen v sesquiterpen bng phng php sc k ct c hiu qu tt nht. Cu 4: Tm hiu nguyn liu cha nhiu Piperitol cng nh Caverol? Tr li: Piperitol khng phn b rng trong t nhin. 1-Piperitol c trong tinh du khuynh dip, c bit l tinh du Eucapiltus bradiata Sieb, dOH

Piperitol c trong tinh du cc loi Andropogaon n . Carvacol c tm thy nhiu trong cy hng chanh, cy hng tho, cy hng ty, cy long no

Piperitol

OH

K u nga thng c gi l: Thng nh, Pht ma, Mc nhng. Tn khoa hc: Xanthium strumarium L, H Cc (ASTERACEAE). Trong l kh c Cha d. carveol (25%). Thuc h cam qut (Rutaceae).: Hoa bi cha trans-carveol(0.19%), v bi cha trans-carveol (0.35%)v cis-carveol (0.10%). Loi Metha citrate ehrh Nam kinh-Trung Quc cha trans-

Carveol

carveol(0.5%)v cis-carveol(0.6%). Cu 5: Tm hiu khung sn Ursan, Oleanan, Lupan, Hopan v Squalan? Tr li:

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Ursan

Oleanan

Lupan

Hopan

Squalan Cu 6: Tm hiu khung sn Caryophyllen? Caryophyllen oxide? Tr li:

Cariophilen

Cariophilen oxit

Cu 7: Azulene c phi l vng thm? Tr li:

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Hp cht thin nhin

Azulene l ng phn ca Naphthalene, cng l hp cht thm c s in t pi l 10 (4n+2)

Tn IUPAC: Bicyclo[5.3.0]decapentaene Cu 8: Tm hiu mt s khung triterpen: mch h ,mch 4 vng nh Dammaran, 5 vng nh Friedelan,taraxeran,lupan,hopan,olean? Tr li: * Mch h:

* 4 vng:

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Hp cht thin nhin

* 5 vng:

Cu 9: Tm hiu s ging v khc ca: triterpen to bt v khng to bt? Tr li: V mt cu trc, triterpen to bt khc vi triterpen khng to bt ch triterpen to bt c cha phn t ng hay chnh l cc glucosid. Triterpen khng to bt c th l mch h, vng cn triterpen to bt l lun lun dng mch vng. Cu 10: Vitamin K, E l g? Lch s, CTCT, CTPT, thuc tnh ha hc, tnh cht, ng dng...?
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Hp cht thin nhin

Tr li: * Vitamin K Vitamin K (cn gi l napthoquinone) l mt loi vitamin tan trong cht bo rt cn thit cho c th chng ta. C 3 dng vitamin K: Vitamin K1 ,K2 ,K3. Lch s pht hin - Nm 1929, Henrik Dam a ra nhn xt rng g con nui bng thc n tng hp c chu chng chy mu ng tiu ha v c. - Nm 1934, Dam chng minh rng c mt yu t hot ng chng chy mu bo v g con khi cc chu chng ni trn l Vitamin K (Koagulation Vitamin), c tnh cht ha tan trong cht bo v dung mi ca cht bo. Cng thc cu to

Vitamin K1 (phylloquinon)

Vitamin K2( menaquinon) Tnh cht vt l

Vitamin K3 (menadion)

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Hp cht thin nhin

Tnh cht ha hc - Tnh cht oxi ha-kh: Vitamin K b kh thnh cc dn xut Hydroquinone v khi oxi ha tr li s chuyn thnh dng Quinone. - Vitamin K phn hy nhanh di tc dng ca tia t ngoi v khi cu trc quinone ca n b bin i. - Khi un nng trong mi trng kim Vitamin K b ph hy nhanh chng. Chc nng sinh hc - Vitamin K xuc tin tac dung trong s ng mau, tham gia vo thnh phn coenzim ca cc enzim xc tc qu trnh to nn Protrombin - loi hp cht protein c vai tr quan trng trong qu trnh ng mu. - Gip ci thin mt xng, ngn nga long xng. - Ngn nga thnh mch b cng, gim nguy c x va ng mch, t gim suy tim v cc bnh tim mch. - Ngn nga soi thn. - iu tri vt thng ngoai da. - Gip chng li bnh Alzheimer. - Gip gim cc vt bm tm. - Can thip vo iu ha ng huyt v tit insulin. - C c tnh chng oxy ha. - Tc dng protein co c miozin v nh hng ln tnh cht co gin v tnh enzim ca miozin, n cn lm tng tnh cht co bp ca d dy v rut. - Vitamin K cn m bo vic vn chuyn electron trong qu trnh quang hp thc vt v qu trnh phosphoryl ha oxi ha ti th ca ng vt. Tng hp Vitamin K1: tng hp Vitamin K1 c th tin hnh phn ng ngng t ca ru Phytol vi dn xut 2-metyl-1,4-naphtohydroquinone nh cc cht xc tc nh Acid Oxalic hoc tt hn dng Kali acid sulfat. Vitamin K2: Khi cy Bact.coli trn mi trng thch c cha Amon Lactat s to c mt lng ln Vitamin K2phng php sn xut Vitamin K2 trong k ngh. Vitamin K3: L cht 2-metyl-1,4-naphtoquinone c Sah (1950) tng hp bng cch metyl ha -naphtylamin v sau oxi ha cht 2-metyl--naphtylamin thu c bng Acid Cromic.
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Hp cht thin nhin

Ngun thc n t nhin c chaVitamin K Lng vitamin K cao nht cc rau l xanh: rau dip, sp l, c ci xanh, ci b; v trong hoa qu, ng cc, ht qu, trng, gn b,. * Vitamin E Vitamin E l tn gi chung ch hai lp cc phn t (bao gm cc tocopherol v cc tocotrienol). N l mt loi Vitamin tan trong du. Trong thc vt, tocopherol c phn phi rng ri nht, c cu trc vng vi mt chui di bo ha bn cnh. Tocopherol gm 4 dng: alpha-, beta-, gamma-, v delta-, chng c phn bit bng s v v tr nhm methyl trn vng. Alpha tocopherol l thnh phn c hot tnh sinh hc nhiu nht ca Vitamin E. Tocotrienol cng c 4 dng, alpha-, beta-, gamma-, v delta-, c phn bit vi tocopherol nh chui bn cnh bt bo ha. Cng cn c gi di tn isoprenoid, cc tocotrienol t c phn b rng ri trong thin nhin. Lch s pht hin Vitamin E c khm ph vo nm 1922 khi cc nh khoa hc pht hin thy chut cng c nui dng vi mt ch n thiu Vitamin E s ny sinh cc vn lin quan n sinh sn. Khi Vitamin E c cng nhn nh l mt hp cht c tc dng phc hi kh nng sinh sn, cc nh khoa hc t cho n tn ha hc l tocopherol, t ting Hy Lp, c ngha l sinh con. Cng thc cu to

Tnh cht vt l v ha hc Vitamin E l cht c dng du lng, khng mu, tan tt trong du thc vt, trong ethanol, eter ethylic v eter du ha. Tocopherol thin nhin c th kt tinh chm trong ru methanol nhit thp khong -35oC. Bn vi nhit , acid, chu c ti 170oC, khng bn trong mi trng kim v b phn hy bi tia t ngoi.
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Hp cht thin nhin

B oxi ha bi FeCl3 hoc acid HNO3 to nn tocopheryl quinone c cu trc ha hc gn ging vi vitamin K v Q. Ngun cung cp vitamin E Trong thc phm, cc ngun ph bin nht cha vitamin E l cc loi du thc vt nh c du, hng dng, ng, u tng, liu. Cc loi qu kin, ht hng dng, qu nht gai , dng o v mm la m cng l cc ngun cung cp vitamin E. Cc ngun khc c ht ng cc, c, b lc, cc loi rau l xanh. Mc d ban u vitamin E c chit ra t du mm la m, nhng phn ln cc ngun b sung vitamin E t nhin hin nay li tch ra t du thc vt, thng thng l du u tng. Chc nng sinh hc i vi ph n mang thai, vitamin E gp phn thun li cho qu trnh mang thai, s pht trin ca thai nhi v gim c t l sy thai hoc sinh non do trung ha hoc lm mt hiu lc ca gc t do trong c th. Vitamin E cng lm gim nh cc triu chng chut rt, au cc bp c hoc au bng khi hnh kinh cc em gi tui v thnh nin. Cc em gi nu c dng vitamin E ngay t u ca k kinh s gim c 36% au khi hnh kinh. Ngoi ra vitamin E cn gp phn ci thin tnh dc, gip non (trng) v tinh trng pht trin tt hn, nng cao kt qu iu tr v sinh Vitamin E c th gip lm gim tin trnh lo ha ca da v tc ci thin tnh trng da kh sm, tc gy rng... Cu 11: Phng php no tch Geraniol v Nerol? Tr li: Geraniol v Nerol l hai ng phn ca nhau ta c th tch chng ra khi hn hp bng cc phng php: Phng php cng hp vi CaCl2: hn hp c Geraniol c cho vo CaCl2 khan nhit phng tt nht l 40C, sau ra sn phm cng hp vi hexan,phn gii vi nc,tch chit sn phm v em chng ct. CaCl2 + nROH CaCl2.n ROH + 6H2O CaCl2.nROH n ROH + CaCl2.6H2O

Phng php to ester vi acid boric ,sau sn phm ester c phn hy vi Na2CO3 hay NaOH long. 3ROH + (RO)3B +
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H3BO3 (RO)3B + 3H2O 3NaOH Na3BO3 + 3ROH 16

Hp cht thin nhin

Cu 12: Tm khung Biflavon? Tr li: Biflavon l mt nhm lin hp cha lin kt flavone-flavone. Agathisflavone
OH O

Isoginkgetin

OH

HO HO O O

O OH OH
HO O HO OH O OH O O OH

OH

Procyanidin B5
OH

OH

Amentoflavone

HO O

OH OH OH
HO

OH O

OH

HO OH

OH HO O

OH
OH O

OH

Rubustaflavone
OH HO O HO OH O OH O HO O

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HO O O HO O O HO OH
OH O HO HO O

Pancibiflavonol
OH
OH

OH
OH O OH

Chamaejasmine
OH O

OH

Hinokiflavon
OH HO O OH O O

HO

Cu 13: Da vo 1H-NMR c phn bit c Kaempferol v Quercetin? Tr li:

2' HO 8 7 6 5 OH 9 O 2 1' 6' 3 4 O OH 3' 4' OH 5'

10

Kaempferol Ph 1H-NMR ca Kaempferl c tn hiu proton ca nhm hydroxyl OH kim ni [

H

12,15 (1H; s)]. Cc mi cn li thuc vng trng thp ca vng thm vi 2

H

proton meta ca vng benzen [ Hz; H-2, 6); 1, 4 nh hon.

H

6,52 (1H; d; J=2,0 Hz; H-8);

6,26 (1H; d; J=9,0

7,01 (2H; d; J=9,0 Hz; H-3, 5)] cho ta d on l ca vng benzen

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Hp cht thin nhin

2' HO 8 7 6 5 OH 9 O 2 1'

OH 3' 4' OH 5' 6'

10 O

3 4 OH

Quercetin Ph 1H-NMR ca Quercetin c tn hiu proton ca nhm hydroxyl OH kim ni [ cp ortho [ 6,99 (1H; d; J=8,0 Hz; H-5);
H H

12,16 (s)], cc mi cn li thuc vng trng thp ca vng thm vi 2 proton ghp
H H

7,69 (1H; d; J=8,0 Hz; H-6)]; v ba

prtoton mi n khc [

6,26 (1H; s; H-6); 6,52 (1H; s; H-8); 7,82 (1H; s; H-2)].

Cu 14: C phi tt c hp cht Flavonoid u c mu hay khng? Cho v d? Tr li: a s cc flavonoid thng kt tinh v c mu. Flavon c mu vng nht hay vng cam; flavonol c mu vng n vng nht; chalcon c mu vng n cam . Ring leucoantocyanidin l flavan-2,4-diol, cc hp cht ny khng mu, khi gp acid s bin thnh antocyandin c mu hng hay mu . V d: Mt hp cht kiu leucoantocyanidin khng mu:
OH OH HO O

OH HO O OH OH

OH OH

OH OH

OH

Melecacidin +(-)Leucorobinetinidin

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Hp cht thin nhin

Isoflavonoid (isoflavon, isoflavanon, rotenoid) tt c khng c mu sc. N c to thnh t axetat theo c ch ng vng vi phenylalamine, cinnamate dn xut c st nhp vo vng B v C-2,-3, v -4 ca d vng. Mt s isoflavonoid khng mu:
O H3CO HO O OH HO

O
Daidzein
HO O

OH

Glycitein
HO O

OH O OCH3

OH

Glycitein

Formononetin

Cc dn xut flavan-3,4-diol u khng mu

V d v flavan-3,4-diol khng mu
O HO OH

3,4-Hydroxylflavan

leucopelargonidin

Catechin v nhng ng phn ca n cng nh gallocatechin v nhng ng phn ca cht ny l nhng dn xut flavan-3-ol gp tng i ph bin trong thc vt.
OH OH HO O OH OH HO O OH OH OH OH

(-)-catechin (2S-3R)
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(-)-Epicatechin (2R-3R 20

Hp cht thin nhin OH OH OH HO O OH OH OH OH O HO O O OH OH OH OH

(+)-catechin (2R-3S)

Gallocatechin Cu 15: Tm quy trnh trch ly v c lp Flavonoid? Tr li: * Tch flavonoid ra bng dung dch acetate ch Cao chit c ha tan trong dung dch 10% ethanol/nc cha trong mt erlen. T t rt vo erlen ny dung dch nc 10% acetate ch , khuy nh u s c kt ta flavonoid. Lc thu ly ta. Ha tan ta li trong dung dch alcol long, khuy nh cho thnh mt dung dch treo ng nht. Rt thm vo dung dch nc bo ha Na2SO4 nhm loi b PbSO4. Lc ly dung dch nc trong, ui nc bng c quay chn khng thu c cao th cha flavonoid ton phn. Sc k ct tch ring cc flavonoid.

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Hp cht thin nhin

Cao chit Ha tan vo etanol 10% Dung dch nc - Dung dch nc acetate ch 10%, khuy u, yn - Lc

Dung dch nc

Ta - Ha tan vo etanol 10% - Thm vo dung dch nc bo ha Na2SO4 - yn. Lc

Ta PbSO4

Dung dch nc C quay chn khng Flavonoid th Sc k ct Cc Flavonoid ring r

Quy trnh chit tch flavonoid ra khi cy c bng dung dch acetate ch * Tch cc flavonoid bng dung dch kim Ha tan cao chit vo dung mi hu c thch hp nh: cloroform, etyl acetat.. Tip theo, thc hin chit lng-lng dung dch ny vi dung dch nc kim 5-10% nh: dung dch borat natri, NaHCO3, Na2CO3 Cc dung dch nc kim c gp chung li v c acid ha. S dng dung mi hu c ph hp chit cc flavonoid ra khi dung dch nc. Lm khan nc bng CaCl2, Na2SO4 ui dung mi thu c cao th cha flavonoid ton phn. Sc k ct tch ring cc flavonoid.

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Hp cht thin nhin

Cao chit - Ha tan vo chloroform hay etyl acetat Dung dch hu c - Thc hin chit lng-lng vi dung dch nc kim 5-10% Pha hu c Pha nc kim

Cha cc flavonoid dng

HO

O O

- Acid ha Pha nc acid

Cha cc flavonoid dng - Thc hin chit lng-lng vi dung mi hu c: chloroform, etyl acetat Pha hu c
O

Pha nc - Lm khan nc - ui dung mi Flavonoid th Sc k ct Cc Flavonoid ring r

Quy trnh chit tch flavonoid ra khi cy c bng dung dch kim Cu 16: Ti sao hu ht Alkaloid u c tnh hot quang v tnh baz, cch tnh quay cc ? Tr li: Trong phn t Alkaloid c cha cc tm nguyn t bt i xng nn c tnh hot quang (ch yu l tm C bt i xng). Phn ln cc alkaloid c tnh hot quang v hu nh ch quay tri. Alkaloid c tnh bazo l do trong phn t c cu to d vng cha Nit (amin). quay cc: s quay ca mt phng phn cc khi chiu nh sng phn cc qua mt cht quang hot. quay cc ph thuc vo nhiu yu t nh chiu dy ca lp cht

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Hp cht thin nhin

o, nh sng s dng, nhit o, dung mi v nng cht tan. c trng cho tnh quang hot ca 1 cht, ngi ta dng quay cc ring tnh theo cng thc:
[] D =

l.C

Trong :

: l gc quang st c ()
l: l di bung cha mu (dm) C: nng (g/ml) Cu 17: Tng hp -Terpineol t Limonen? Tr li:

Cu 18: Gii thch s xut hin ca cc bng hp th? Tr li: S xut hin ca bng hp th ca monoterpen v sesquiterpen trong ph UV l do trong cu trc phn t c dy ni i lin hp, hay ni i. Thng th cc hydrocarbon c bng hp th khong 219-289nm, cc dn xut c cha nhm carbonyl th hp th bc x cao hn khong 305nm. Trong ph hng ngoi IR cc ni i C=C thng t c ch v trng vi cc peak khc. Cc dn xut c cha oxy nh: alcohol, ketone, acid carboxylic. th c cc peak c trng ca tng loi nhm chc. V d cc hp cht cha lien kt C=O c peak mnh trong vng 1820- 1640cm-1. Cu 19: Tm hiu s sinh tng hp alkaloid? Tr li: Vn sinh tng hp cc alkaloid c nhiu nh khoa hc quang tm. Nm 1912 Trier a ra gi thuyt rng sing tng hp cc alkaloid gn lin vi s chuyn ha amini axit ca protein trong cy. Gn y c thuyt cho rng cc aldehit hnh thnh t
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Hp cht thin nhin

cc monosaccarit ngng t vi amin hoc amoniac thnh cc d vng cha nit (alkaloid). C th tng qut nh sau:

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Hp cht thin nhin

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