4/18/2012

Hp chat d vong

1. nh ngha nh ng h p ch t vng c t o thnh khng nh ng do cc nguyn t carbon m cn c cc nguyn t khc nh N, O, S, B, Al, Si, P, Au, Cu, nhng ph bi n v quan tr ng hn l cc d t N, O, S. 2. Phn lo i - D vng khng thm: no ho c cha no - D vng thm : c u trc i n t ph h p Huckel (4n+2) e.
D vng 5,6,7 c nh 1 d t D vng 5,6,7 c nh 2 d t

* furan, thiophen, pyrrol * 2 d t gi ng nhau: pyrazol ... * ngng t v i benzen: benzofuran * 2 d t khc nhau: oxazol, thiazol. * Ngng t v i benzen: benzothiazol.

4/18/2012

3. Danh php 3.1. Danh php thng th ng xu t pht t ngu n g c v tnh ch t c a h p ch t. khng ph n nh c u trc phn t nhng tr thnh ph bi n nh 1 quy c c a h th ng danh php IUPAC.

N N H Pyrrol O Furan S Thiofen N H Pyrazol N N O N H N N H Imidazol N O N N H Pyrroldin H N O

Furazan H N N H

N N N N N

Pyridin Pyridazin

Pyrimidin Pyrazin -Pyran Piperidin Piperazin Morpholin N H N N H Indazol N N N N N N N N H Purin N N Quinolizin O Chroman N N Indolizin

N H Indol

Isoindol

N Quinolin

N Isoquinolin

N Quinazolin N

Pteridin S N H

N H Carbazol

N Phenazin

Phenothiazin

Phenanthridin

4/18/2012

3.2. Danh php h th ng- Danh php Hantzsh-Widman

Tn d vng = ti p u ng (d t ) + thn (khung, l n vng)

* Ti p u ng cc d t : Oxy : Lu hynh: Nit: * Tn ph n thn cc vng n: l n Vng khng c N c a vng Vng cha no Vng no 3 4 5 6 7 8 iren et ol in epin ocin iran etan olan inan epan ocan

Oxa Thia Aza Vng c N

Vng cha no irin et ol in epin ocin

Vng no iridin etidin olidin perhydro perhydro perhydro

Nguyn t c nh s : - nhi u d t : nh s u tin theo th t O > S > N > P - nh s vng t d t sao cho t ng s v tr nh nh t.
S O
1

N3 N

1O

NH
2

Thieren
3O

Oxiran

1,3-Diazet N4 N2

1,2-Oxazetidin

1O

N1

S Thiepan

1,3-Dioxolan

1,2,4-Triazin

* Khi vng c s n i i c c i c no ha d n th v tr nguyn t bo ha c g i v i ti p u ng H km theo tn c a d vng cha no (v i s n i i c c i) tng ng.

H N1 O 1H-Azirin N
2 3

N 3H-Azepin

2H-1,3-Oxazin

4/18/2012

3.3. Danh php h th ng vng ngng t Nguyn t c g i tn: N

N Pyrrolo[1,2-a]pyrimidin

Thnh ph n th 2

Thnh ph n c s

* Thnh ph n th 2: l ti p u ng c a thnh ph Tn = tn d vng + o M t s ngo i l v V d : pyrazin pyrazino Tn d vng pyrrol pyrrolo Furan thiazol thiazolo Imidazol oxazol oxazolo Isoquinolin
Pyridin Quinolin Thiophen

n c s ti p u ng
Ti p u ng Furo Imidazo Isoquino Pyrido Quino Thieno

* Thnh ph n c s : Ch n theo th t sau: - Ch n d vng ch a nit (n u khng c N th theo th t ) - Ch n vng ngng t c nhi u vng ho c vng l n hn. - Ch n vng c nhi u d t v u tin theo th t . - Cc vng cng d t v l n th u tin cch nh s nh hn. V d :
N N Imidazo[2,1-b]oxazol O
3

N1 Imidazo
4 5

aO

O N

H N N

N Oxazol
b

aO d bN c

3 4

H N2 N1
5

1H -Pyrazolo[4,3-d]oxazol N N N N

Oxazol
aN

Pyrazolo
3 N 4

3N

2 1

aN

d + c

1N

Imidazo[1,5-b]pyridazin

Imidazo

Pyridazin

Pyrazino[2,3-d]pyridazin Pyridazin

Pyrazino

4/18/2012

nh s trn d vng ngng t - Xu t pht t nguyn t c nh nguyn t u c u theo chi u sao cho cc d t c s nh nh t. - N u khng th a mn th d t u tin c nh s b nh t. V d : 6 H H
O
5 4N

N1 N2
3

aO d bN c

N2 N1
5

1H -Pyrazolo[4,3-d]oxazol
8 7N 6N 5

Oxazol N N

Pyrazolo
3 N 4

1 2 3 a d c

N4

1N

Pyrazino[2,3-d]pyridazin
7 6 5N

Pyridazin
5 4

Pyrazino N
aN

8 N1

N1
2 3

N4 3

N 1,2,4-triazin

Imidazo[1,2-b]-1,2,4-triazin

Imidazo

5H-Pyrido[2,3-d]-o-oxazin

4H-Imidazo[4,5-d]thiazol

Imidazo[2,1-b]thiazol Furo[3,4-c]cinnolin

4/18/2012

3.4. Danh php th Xem h p ch t d vng l cc hydrocarbon trong 1 hay nhi u nguyn t carbon c thay th b i cc nguyn t khc.
O N N Azabenzen N 1,3-Diazabenzen
6 5 1 7 4 3 2

7-Oxabicyclo[2,2,1]-2,5-heptadien

Hp chat d vong 5 canh 1 d to

Cc d vng 5 c nh 1 d t thng d ng
O Furan S Thiophen N H Pyrrol

Xt Pyrrol i i n t t do trn N tham gia lin h p 4n + 2 = 6 e thm i i n t khng linh ng khng c tnh base, c tnh acid Nng l ng thm ha Furan 16,2 kcal.mol-1 Pyrrol 21,6 kcal.mol-1 Thiophen: 29,1 kcal.mol-1 Benzen 35,9 kcal.mol-1 Tnh thm: Furan < Pyrrol < Thiophen < Benzen

4/18/2012

Furan, Pyrrol, Thiophen khng th hi n tnh ch t c a ether, amin v sulfur. Cc d vng thm 5 c nh th hi n tnh ch t hydrocarbon thm - th i i n t : NO2 ha, SO3H ha, X2 ha, Fiedel-Crafts
E H E+ X X X X E H X E

E H X

E H X

E H X E

Th i i n t vo d vng thm 5 c nh: u tin v tr 2. M i d vng thm c nh ng i u ki n ph n ng th i i n t khc nhau. Kh nng th i i n t theo th t pyrrol > furan > thiophen > benzen

Furan
4 5
O
1 3

Ch t l ng khng mu, ts 31oC, khng tan/ H2O, tan t t/alcol, ether.

1. T ng h p Dehydrat ha 1,4-dicarbonyl
R C O C R' O R C OH C R' OH R O R' + 2H2O

Ngng t -halogenoceton v i -cetoester

R C O + Cl O C COOC2H5 R' R COOC2H5 + O R' H2O + HCl

2. Tnh ch t ha h c Tnh thm y u, th hi n tnh ch t c a 1,3-dien.

4/18/2012

- Hydro hoa tao THF (tetrahydrofuran) + O 2H 2 xt O O O + O - Phan ng the ai ien t Cl 2 O CH 3 COONO 2 O Pyridin . SO 3 O (CH 3CO )2 O O H gCl 2 CH 3 COONa + O HgCl HCl COCH 3 O SO 3 H N O2 Cl + HCl O O O O O

- Phan ng Diels-Alder

C H 3 C OO H

Pyridin

C H 3 C OO H

3. D n xu t c a furan * Furfural: furan-2-aldehyd

(C5H8O4)n H2O, H
+

CHO (CHOH)3 CH2OH

-3H2O O CHO

- Ha tnh

HNO3, H 2SO4 (CH 3CO)2O KOH () O CH2OH O2 N O CHO

CHO

+ O COOH

H2N-HN-C-NH2

nh tnh anilin
Ph-NH2 + O CHO Ph NH2

O (S)

CH=N-HN-C-NH2 O (S)

CHO

+ PhNH2, + HCl -H2O

Ph

N H

N OH Ph

Cl

* M t s thu c c ch a furan
O2N O CH=N

O NH O O2N O CH=NNHCONH2

Nitrofurantoin

Nitrofurazon

4/18/2012

Ch t l ng, ts 130 oC, t tan /H2O, tan t t trong alcol, benzen, ether, mi gi ng nh CHCl3. C p i n t tham gia lin h p nhn thm tnh base gi m. Khi b m t proton H+, pyrrol b n hn do c ng h ng tnh acid.
N H
N N N N N N

Pyrrol

1. T ng h p vng pyrrol - Phng php Knorr

R C O C R' O R C OH H C R' OH R N R" R' + 2H2O

H N R"

- T acetylen, aldehyd formic v amoniac (amin b c 1)

HC CH + 2HCHO Cu2Cl2 HOH2C-C C-CH2OH NH 3, p N H

2. Ha tnh - Tnh acid-base: pyrrol c tnh acid y u.

KOH -H2O N H RMgBr -RH N MgBr N K

CO2 to, p N K RCOCl

N H

COOK to

N R C O

N H

C O

- Ph n ng th i i n t Nh furan, thiophen ph n ng th i i n t ch y u x y ra v tr 2, c th nitro ha b ng HNO3/ (CH3CO)2O, sulfonic ha b ng SO3/ pyridin

4/18/2012

SO2Cl2 N H HCON(CH3)2 POCl3 CHCl3 , 3KOH N H

+ [C6H5N N] Cl

Cl

+ SO2 +

HCl

N H

CHO

+ HN(CH3)2

N H N H I2/KI I I N H I

CHO

+ 3KCl + 2H2O

N=N-C6H5

+ HCl

+ HI I

- Ph n ng c ng: d tham gia

2[H] N H N H 3-pyrrolin 2[H] N H pyrrolidin

* Benzopyrol (Indol) Indol c th c t ng h p theo nhi u cch

R2 R1 N H N ZnCl2 -NH3 N H R2 R1

Cc h p ch t c ch a nhn indol
CH2CHCOOH NH2 N H Tryptophan N H Serotonin CH2 CH2NH2

Indomethacin

Melatonin

10

4/18/2012

Thiophen

Ch t l ng, ts 84 oC, c mi nh gi ng benzen, khng tan/ H2O, h n ha v i ph n l n DM h u c.

1. T ng h p thiophen - h p ch t 1,4-dicarbonyl
R C O C R' O R C OH C R' OH H2S R S R' + 2H2O

- -clorovinylcarbonyl ngng t v i ester c a acid thioglycolic.

R2 R1 C Cl C CHO + COOC2H5 SH R1 R2 + H2O + HCl COOC2H5

2. Tnh ch t ha h c C tnh thm m nh hn furan v pyrrol. Tham gia ph n ng th i i n t nhng ch m hn so v i furan v nhanh hn benzen.
NBS S HNO3/(CH3CO)2O S S H2SO4 S RCOCl/AlCl3 S COR SO3H NO2 Br

hydro ha c xc tc t o thiolan
2[H] S S 2[H] S

11

4/18/2012

D n ch t c ch a nhn thiophen: Benzo[b]thiophen

S

ng d ng trong cng ngh ch t d o v lu ha cao su.

Raloxifen

Zileuton

Sertaconazol

* Cc d vng 5 c nh furan, pyrrol v thiophen c th chuy n ha l n nhau.

S H2S NH 3 H2O N H NH3 O H2S H2O

12

4/18/2012

D vong 6 canh 1 d to
1. Pyridin
1. C u t o: Pyridin (azin) l ch t l ng c mi kh ch u, ts 115 oC, tan t t trong n c 3 v cc dung mi h u c, l dung mi cho 5 4 nhi u h p ch t v c v h u c. N gp thm 1 i n t t o h th ng vng thm theo Huckel. N cn d i i n t t do, nn c tnh base. N l nhm th lo i II (h ho t), nn ph n ng th i i n t (SE) kh x y ra (3,5) v ph n ng i nhn (SN) d x y ra (2,4,6)
1 6 N 2

N
4

2. i u ch - Pyridin c trong nh a than (kho ng 0,1%) - trng h p v i acetylen v acid cyanhydric

CH CH + H CN CH CH N

- ngng t t aldehyd cha no v i NH3

CH3 2CH2=CH-CHO + NH3 -2H2O N

- ngng t -cetoester v i aldehyd v NH3-ph n ng Hantzsch

R' R' C2H5OOC R O NH3 CHO + O R COOC2H5 -3H2O, -2[H] -2C2H5OH, -2CO2 R N R

13

4/18/2012

Amlodipin
3-Ethyl 5-methyl 2-(2-aminoethoxy methyl)-4-(2-chlorophenyl)-1,4-dihydro6-methylpyridin-3,5-dicarboxylat

Felodipin
Ethyl methyl 4-(2,3-dichlorophenyl)1,4-dihydro-2,6-dimethylpyridin-3,5dicarboxylat

3. Tnh ch t ha h c 3.1. Tnh base: c tnh base y u

N N H N-methylpyridinium iodid N N CH3 H3C N CH3 H N
+

Cl

Pyridin clohydrat

H3C

CH3

H3C

CH3

N H

N H

4-dimethylaminopyridin (DMAP) lm xc tc (base) trong cc ph n ng l p th .

14

4/18/2012

3.2. Ph n ng th i i n t SE - ch m v kh hn so v i benzen (v N h ho t) - ph n ng s th v tr 3 v 5 - khng tham gia ph n ng Friedel-Crafts (alkyl, acyl ha) - halogen (clor, brom, iod) ha pyridin 300 oC s cho h n h p mono v di-halogeno
H2SO4 + KNO3 300 oC H2SO4 + SO3 N 230 oC Br2 300 oC N N Br + HBr N SO3H + H2O NO2 + H2O

3.3. Ph n ng th i nhn (SN) - ph n ng th x y ra v tr 2, 4 v 6.

NaNH2 N N C4H9Li N C4H9 NH2 + NaH

+ LiH

- Cc d n xu t pyridin cng d tham gia ph n ng th i nhn

NH3 N Cl CH3ONa N OH-, H2O N Cl N OH N + ClBr 180-200 oC N NH2 + HBr

OCH3 + NaCl

15

4/18/2012

3.4. Ph n ng oxi ha
-Picolin
N CH3 CH3 3[O] + N COOH COOH + H 2O N COOH 3[O] + N H2O2 30% N CH3COOH N O NO2 HNO3 H2SO4 N H 2O H2O

Acid picolic

-Picolin
N CH3

3[O]

Acid nicotinic

-Picolin

Acid isonicotinic

+ H 2O

N-oxyd pyridin

N O

N O

R a N O

N a = H2/Ni hay Fe/H+ hay PCl3

3.5. Ph n ng kh - c th b ng H2, xc tc, hay Na/C2H5OH, LiAlH4

b N H b = H2/Pd hoac Na/C2H5OH N b N H b N H

* M t s ch t ch a nhn pyridin
O C N Vitamin PP Dimethylnicotinamid O N(CH3)2 N Isoniazid, Rimifon Isonicotinhydrazid C NH-NH2 HOH2C CH2OH OH N Vitamn B6 Pyridoxin CH3 N N CH3 Nicotin N CH3

CH2OH OCOCH Atropin C6H5

16

4/18/2012

Quinolin- benzo[b]pyridin
5 6 7 8 1 4 3 2

Quinolin l ch t l ng, ts 238 oC c trong nh a than . Tnh ch t g n gi ng naphthalen v pyridin.

1. T ng h p: - Phng php Skraup

+ NH2 CH2OH CHOH CH2OH + C 6H5NO2 H2SO4, FeSO4 N + C6H5NH2 + H2O

- Phng php Friedlander

CHO + NH2 CH3 CHO -H2O N CHO CH3 CH -H2O N

2. Ha tnh - Ph n ng th i i n t : gi ng nh naphthalen, v tr 5,8. - Ph n ng th i nhn gi ng nh pyridin, v tr 2,4

HNO3 H2SO4
8

NO2 SO3 N H2SO4 N 8 SO3H

2

NaNH2 N

NH2

8-hydroxyquinolin dng trong phn tch h u c cng nh tch cc ion kim lo i nh Al3+, Mg2+, Zn2+.
N M O N O

N O H

17

4/18/2012

3. Cc alkaloid c ch a quinolin
H3C CHCH2CH2CH2N(C2H5)2 NH H3CO N NH H3C CHCH2CH2CH2N(C2H5)2 Plasmoquin CH=CH2 H H3CO HO H N

Cl

N Cloroquin

N Quinin

Isoquinolin- benzo[c]pyridin
5 6 7 8 1 4 3

N2

Ch t l ng, ts 243 oC mi hng gi ng v i mi c a h n h p d u h i v benzen, h u nh khng tan trong n c, tan trong acid long, h n ha v i nhi u dung mi h u c. Tnh base m nh hn quinolin.

1. T ng h p - ng vng c a base Schiff trong H+ r i kh ha

NH2 RCHO -H2O HCl HC R N R NH Pd -4H R N

- ng vng amid trong H+

P2O5 O NH CH3 t
o

Pd N CH3 N CH3

18

4/18/2012

Cc alkaloid c ch a khung isoquinolin

H3CO H3CO N CH2 H3CO H3CO N CH2 CH3 O O H3CO HC N CH3 O

OCH3 OCH3 Papaverin

OCH3 OCH3 Laudanosin

OCH3 OCH3 Narcotin

Morphin

Berberin

2. Pyran

Pyran c 2 d ng: -pyran v -pyran, c 2 khng c tnh thm. Trong thin nhin t n O O -Pyran -Pyran t i ch y u d i d ng -pyron, -pyron, 2H-pyran 4H-pyran benzopyron (coumarin), -benzopyron. * -Pyran: th ng g p d ng

O O O O O

-Pyron

-Chromen

Coumarin (2H-benzopyran-2-on)

t ng h p coumarin
CHO OH (CH3CO)2O CH3COONa O O

Ch t c ch a nhn coumarin

OH C6H5 CHCH2COCH3 O O

Warfarin

19

4/18/2012

* -Pyran:
O O O O OH O O O O

-Pyron

-Chromon

Flavon

Flavonol

Cc flavon v flavonol th ng c ho t tnh sinh h c.

OH O OH HO O OH OH Quercetin Kaempferol HO O OH OH O OH

Epigallocatechin gallat

D vong 5 canh nhieu d to

Cc d vng 5 c nh 2 d t
4 5

N3
2 5

4 5

N3
2 5

4 5

N3
2

4 5

N2 O
1

N2 S
1

N2 N1 H

O
1

N1 H Imidazol

Oxazol

Isoxazol

Thiazol

Isothiazol

Pyrazol

* Oxazol 1. T ng h p - Ngng t -bromoceton v i amid

C6H5 C O H2C Br C6H5 C OH HC Br NH + HO CH O 4-Phenyloxazol C6H5 N

- Ngng t nitrilmandelic v i aldehyd thm

C C6H 5 C H N + OH O N CH C6H5 C6H5 O C 6H5

2,5-Diphenyloxazol

20

4/18/2012

* Thiazol: ch t l ng khng mu, ts 117 oC - Ngng t cloroacetaldehyd v i thioformamid

HC O H2C Cl + S NH2 CH N S Thiazol N S NH2 2-Aminothiazol

HC O H2C Cl

+ S

NH2 C NH2

Thiazol c trong c u trc m t s ho t ch t sau:

N H3C S NH SO2 NH2 HOH2CH2C N NH2 N 2ClN CH3 S H Vitamin B1 (thiamin) S N Penicillin

Sulfathiazol

MeON N H2N S

H N O N

S CH2OH COOH

ROCHN

CH3 CH3 COOH

Cefotaxim

* Imidazol - un nng glyoxal (dicarbonyl) v i NH3 v aldehyd

R R C O + R C O NH3 NH3 + O CH R' -3H2O R N H N R'

- Ngng t -aminonitril v i aldehyd thm

C C6H5 CH NH2 N + O CH C6H5 C6H5 N H N C6H5

Imidazol c lin k t hydro lin phn t nn ts cao.

NH N HN N HN N HN N

M t s d c ph m c nhn imidazol
CH2CH2OH O2N N N Metronidazol CH3 Cl N H3C HN CH2SHCH2CH2NHCNHCH3 N N C N H3CO H N N O S H3C N CH3 OCH3

N Clotrimazol

Tagamet (Cimetidin)

Losec (Omeprazol)

21

4/18/2012

* Pyrazol - Ngng t d n xu t c a hydrazin v i 1,3-dicarbonyl

R R O R O + NH2 R N N R' R'

HN

- C ng h p diazoalkan v i alkyn
R R C R' CH N N C R R' R' CH N N N H

R N

Khung 5-pyrazolon l khung c b n c a m t s thu c h nhi t

CF3 CH3 O N N H O N CH 3 (H3C)2N O CH3 N N N N CH 3 H3C N

C6H5

C6H5 SO 2NH2

5-Pyrazolon

Antipyrin

Pyramidon

Celecoxib

D vong 6 canh nhieu d to

M t s h p ch t d vng 6 c nh 2 d t
N N N N 1,3-Diazin Pyrimidin N N 1,4-Diazin Pyrazin N N Quinoxalin S 1,4-Thiazin O O 1,4-dioxan S Phenothiazin O O 1,4-dioxin H N H N

1,2-Diazin Pyridazin

N N N N Quinazolin

Cinnolin

H p ch t d vng thm 6 c nh ch a 2, 3, 4 nguyn t N l cc diazin, triainz, tetrazin. Cc ch t quan tr ng l pyridazin, pyrimidin, pyrazin. Cc benzodiazin l cinnolin, quinazolin, quinoxalin. Cc d vng ch a O, N v S, N th ng khng thm.

22

4/18/2012

Hp chat d vong 2 d to Nit

N N

1,2-Diazin Pyridazin

1. Pyridazin: ch t l ng, ts 207 oC, l m t base y u. - T ng h p pyridazin

R R O O H2N-NH2 -H2O R N N R

- M t s ho t ch t c nhn pyridazin
O N H N H3C Minaprin Nifurprazin NO2 O N N N N NH2

N N 1,3-Diazin Pyrimidin

2. Pyrimidin: ch t r n, tnc 22,5 oC, ts 124 oC, l base y u. T ng h p: - Ngng t ure (thioure) v i 1,3-dicarbonyl
R C R C O O + NH2 C H2N S -H2O R N R NH S R N R N SH

- T malonat v ure
O COOC2H 5 H2C COOC2H 5 + H 2N H 2N C O -2C 2H5OH O N H NH O HO N OH N OH POCl 3 Cl N Cl N Cl 6H (Zn) N N

D n xu t c a pyrimidin l acid barbituric

R R' O C C C O NH C O NH

R=R= C2H5 : Veronal R = C2H5, R = C6H5 : Luminal

OH N N OH H 3C N OH N OH N NH2 N OH

Pyrimidin c trong c u trc c a cc acid nucleic

Uracil

Thymin

Cytosin

23

4/18/2012

N N 1,4-Diazin Pyrazin

3. Pyrazin: T ng h p - Ngng t 2 phn t -aminoceton

R C O + NH2 O H2N C R -2H2O R N N R -2H R N N R

- Ngng t 1,2-diamino v 1,2-dicarbonyl

NH2 + NH2 O R O R -2H2O N N R R -2H N N R R

Kh ha pyrazin c piperazin thu c tr giun.

N N Pyrazin 6H H N N H Piperazin

O N N Pyrazinamid NH2

Hp chat d vong cha 2 d to N va S

H N S
9 8 7 6

H 1 N 10 S
5 4

2 3

Phenothiazin T ng h p
H N + S AlCl3 hay I2 H N S

Cc ho t ch t ch a phenothiazin
N (H3C)2N S BrN(CH3)2 Xanh metylen

Ho t ch t Alimemazin Fenoverin Promazin Promethazin

Cng d ng Khng histamin Ch ng co th t An th n, ch ng nn Khng histamin an th n

CH3

R
-CH2CHCH2 N(CH3 )2 O C CH2 N O N CH2 O

R N 10 S

-CH2CH2CH2N(CH3 )2

CH3 -CH2CHN(CH3 )2

24

4/18/2012

Hp chat d vong 7 canh

Cc h p ch t d vng 7 c nh c d t N, O v S n gi n.

N H 1H-azepin

O Oxepin

S Thiepin

Cc ch t ng d ng trong d c ph m
H 3C N CH3 O N Cl N CH3 Dibenzepin Diazepam Clordiazepoxid Nitrazepam Oxazepam N Cl N O O2N N Cl N H 3C N O N HN CH3 H N O H N O OH

ch ng tr m c m an th n, thu c ng

an th n an th n, ch ng co gi t

an th n

Hp chat d vong ngng tu

6 1N 2 5

Purin: Imidazo[5,4-d]pyrimidin
N7
8

N 4 N 9 3 H

Purin l khung d vng ngng t c b n c a nhi u h p ch t trong thin nhin

OH N N N N H OH HO N N N H OH N N N N H NH2 N H2N N N N H OH N

HO

Acid uric 2,6,8-trihydroxypurin

Xanthin 2,6-dihydroxypurin

Adenin 6-aminopurin

Guanin 2-amino-6-hydroxypurin

M t s alkaloid c nhn purin

O HN O N CH3 N N CH3 H3C O N N CH3 Cafein 1,3,7-trimethylxanthin N O N CH3 H3C O N N CH3 N H O N

Theobromin 3,7-dimethylxanthin

Theophylin 1,3-dimethylxanthin

25

4/18/2012

Acid nucleic

1. nh ngha Acid nucleic l polyester c a acid phosphoric (H3PO4) ng pentose (D-(-)-ribose v D-(-)-2-Deoxyribose) base h u c (purin v pyrinmidin).

ng + Base h u c

ng Base h u c nucleosid

Phosphat H3PO4 ng Base h u c nucleotid Nhi u nucleotid Acid nucleic

26

4/18/2012

1. Ph n ng: trong acid nucleic l pentose ng trong ARN (Acid RiboNucleic) l D-ribose ng trong ADN (Acid DeoxyriboNucleic) l D-2-deoxyribose.
1' 1' 5'

H H H

2'

CHO OH OH OH CH2OH
5'

HOH2C

4' 3'

O
2'

1'

OH

H H H

2'

OH D-Ribose

OH

CHO H OH OH CH2OH
5'

5'

HOH 2C 4'
3'

O
2'

1'

OH

OH D-2'-Deoxyribose

2. Ph n base h u c C 4 base h u c khc nhau trong nucleotid. Hai c nhn purin (adenin v guanin) Hai c nhn pyrimidin (cytosin v thymin) Adenin, guanin, thymin v cytosin xu t hi n trong ADN, nhng trong ARN thymin c thay b ng uracil.
NH2 N N Adenin NH2 N O N H Cytosin HN O N H Thymin O CH3 HN O N H Uracil N H N HN H2N N Guanin O N H O N

27

4/18/2012

3. C u t o nucleosid Lin k t nucleosid t o thnh do C1 c a ribose v N3 c a pyrimidin. Lin k t nucleosid t o thnh do C1 c a ribose v N9 c a purin.
NH2 N O
5' 3

O HN HN
3

O CH3 N
1' 3' 2' 3

N
5' 1'

O HOH 2C
4' 3'

N
1' 2'

O
5'

HOH2C

4' 3'

O
2'

HOH2C

4'

OH Cytidin

OH

OH Uridin NH2 N
9

OH

OH Thymidin O

N N N
1' 2' 5'

HN H2N
4' 3'

N N N
1' 2' 9

5'

HOH2C

4' 3'

HOH2C

OH

OH

OH

OH

Adenosin

Guanosin

4. C u t o nucleotid Tn v c u trc c a 4 deoxyribosenucleotid

NH2 N OH
5'

O N HN OH
5'

N N N
1' 2'

N
4' 3'

N
1' 2'

H2N
4' 3'

O=POH2C OH

O=POH2C OH

OH 2'-Deoxyadenosin 5'-phosphat NH2 N OH

5'

OH 2'-Deoxyguanosin 5'-phosphat O HN N
1' 2'

CH3 N
1'

O
4' 3'

OH
5'

O
4' 3'

O=POH2C OH

O=POH2C OH

O
2'

OH 2'-Deoxycytidin 5'-phosphat

OH 2'-Deoxythymidin 5'-phosphat

28

4/18/2012

Tn v c u trc c a 4 ribonucleotid
NH2 N OH
5'

O N HN OH
5'

N N N
1' 2'

N
4' 3'

N
1' 2'

H2N
4' 3'

O=POH2C OH

O=POH2C OH

OH

OH

OH

OH

Adenosin 5'-phosphat NH2 N OH

5'

Guanosin 5'-phosphat O HN

O
4' 3'

N
1' 2'

OH
5'

O
4' 3'

N
1' 2'

O=POH2C OH

O=POH2C OH

OH

OH

OH

OH

Cytidin 5'-phosphat

Uridin 5'-phosphat

5. C u t o acid nucleic Cc nucleotid lin k t v i nhau trong ADN v ARN b ng lin k t ester phosphat gi a nhm 5-phosphat trn 1 nucleotid v i nhm 3-hydroxy c a 1 nucleotid khc. K t thc b ng m t u 3-hydroxy t do v 5-phosphat t do. 5 Base Phosph 5' O O=POH2C 1' at OH 3' n Base h u Base O g c 5' Phosph O O=POH2C 1' at OH 3' n Base h u Base O g c 5' O O=POH2C Phosph 1' OH at 3' n Base h u O g c 3

29

4/18/2012

TERPEN

nh ngha & phan loai

Hydrocarbon cha no c cng th c chung (C5H8)n T o thnh b ng cc n v isopren lin k t v i nhau d ng m ch th ng hay vng theo nguyn t c c ng h p u ui.
nC5H8 n H2C C CH CH2 CH3 (C5H8)n CH2 C CH CH2 n CH3

+ au uoi au uoi Monoterpen

Isopren

30

4/18/2012

Phn lo i terpen d a trn gi tr n: n=1 Hemiterpen n=2 Monoterpen n=3 Sesquiterpen n=4 Diterpen n=6 Triterpen n=8 Tetraterpen n=n Polyterpen

C5H8 (C5H8)2 (C5H8)3 (C5H8)4 (C5H8)6 (C5H8)8 (C5H8)n

Terpen trong thin nhin ch y u trong tinh d u. Trong tinh d u, terpen c thm cc d n xu t c oxy nh alcol, aldehyd, ceton v acid, g i chung l terpenoid. Terpenoid c u t o: khng vng, n vng, a vng.

Monoterpen (C5H8)2
C 3 lo i monoterpen: - khng vng (c 3 lin k t i) - 1 vng (c 2 lin k t i) - 2 vng (c 1 lin k t i) 1. Monoterpen khng vng:
3 4 5 6 7 2 1 4 5 6 7 3 2 1

7-Methyl-3-methylen-1,6-octadien -Myrcen

3,7-Dimethyl-1,3,7-octatrien -Ocimen

31

4/18/2012

Cc d n xu t c oxy c a monoterpen khng vng

3 4 5 6 7 2 1

OH CH2OH CH2OH

CH2OH

Geraniol

Nerol

Linalol

Citronellol

Thnh ph n ch y u trong tinh d u: hoa h ng, cam, chanh, s ,

CHO CHO CHO

Geranial, Citral a

Neral, Citral b

Citronellal

Citral, citronellal c nhi u trong tinh d u s , b ch n

Quy trnh t ng h p ionon t citral a (geranial)

CHO H 3C C CH3 O -H2O

CHO

H+

Citral A O

- H+

-Ionon

-Ionon

32

4/18/2012

Monoterpen 1 vng
Monoterpen 1 vng c khung p-cymen ho c p-mentan, ni chung l mentadien. 7
6 5 1 4 2 3

10

p-Mentan

M t s monoterpen 1 vng

Limonen

-Terpinen

-Terpinen

-Terpinen

Cc d n xu t c a monoterpen 1 vng * Alcol vng no

OH OH OH O OH

Menthol

Carvomenthol

cis-1,8-Terpin

1,8-Cineol

* Alcol vng c 1 lin k t i

OH OH

OH

-Terpineol

-Terpineol

-Terpineol

33

4/18/2012

Monoterpen 2 vng
C u t o c b n c a monoterpen 2 vng c cc lo i vng sau: Caran Thuyan Pinan Camphan Iso-Camphan Fenchan Iso-Bornilan

Caran

Thuyan

Pinan

Camphan

iso-Camphan

Fenchan

iso-Bornilan

Trong 2 dy pinan v camphan l c nhi u ng d ng nh t.

Nhm pinan: Pinen: thnh ph n ch y u c a tinh d u thng. -Pinen chi m 6590%, -pinen chi m 5-20%.

-Pinen

-Pinen

Nhm camphan:
H3 C O CH3 CH3 O OH H3C CH3 CH3 OH

Camphor
H3C CH3 CH2SO3H O H3C

Borneol
CH2SO3H CH3 O

Acid 10-camphorsulfonic

Acid 8-camphorsulfonic

34

4/18/2012

Sesquiterpen (C5H8)3
Guaiazulen Khung azulen c mu xanh hay tm. M t h p ch t azulen tiu bi u l guaiazulen, d n xu t oxy c a chng l guaiol

OH

Azulen

Guaiazulen

Guaiol

Diterpen (C5H8)4
C 2 lo i: khng vng v vng Diterpen khng vng Phytol: CTPT C20H40O, l m t ph n c u trc c a vitamin E v K.
CH3
16

CH3
11

CH3

CH3
3 2 1

H3C

CH2OH

Phytol [(2E),(7R,11R)-3,7,11,15-tetramethyl-2-hexadecenol]
O CH3 CH3 O CH3 CH3 CH3 CH3

Vitamin K1 (2-methy-3-phytyl-1,4-naphthoquinon)
CH3 HO CH3 H3C CH3 O CH3 CH3 CH3 CH3

-Tocopherol

35

4/18/2012

Tetraterpen (C5H8)8
Carotenoid: ch t mu th c v t hay ng v t c mu vng hay vng cam. Carotenoid k t h p v i H2SO4 v dd SbCl3 trong CHCl3 t o mu xanh m (ph n ng Carr-Price). * Caroten

-Caroten

-Caroten

-Caroten

* Licopen

Licopen

* Vitamin A
CH2OH CH2OH

Vitamin A1

Vitamin A2

36

4/18/2012

Polyterpen
Cao su thin nhin Cao su t ng h p * Cao su Buna: Buna N, Buna S * Cao su Butyl * Neopren * Cao su silicon

Steroid

37

4/18/2012

* Steroid l nhm h p ch t c c u trc tng t nhau c trong ng v t v th c v t. * Steroid g m cc lo i h p ch t nh sterol vitamin D, acid m t, cc hormon sinh d c, hormon tuy n th ng th n,
3 4 5 6 7 8 9 10 1

CH3
2

R
12 11 13 17

Hydrocarbon Diels

C
1 2 10 9 8

16 15

14

A
3 4 5

B
7 6

Cyclopentanoperhydrophenanthren

* nh s trn khung steroid

21 20 22 23 24 17 13 14 9 10 5 4 6 8 7 16 15 27 26 25

18

CH3

12 19 11

CH3
1 2 3

Trn khung Cholestan

* C u hnh, danh php v c u d ng c a khung steroid Khung steroid no c ngu n g c thin nhin chia lm 2 dy:

38

4/18/2012

R CH3 CH3
2 1 10 5 3 9

H CH3 H H CH3
13 14

R CH3 H H

H 13

17 14

H R
17 1

CH3
10 9

H
8

CH3
13 14

R
17

CH3

H
8

e
3

1 5

10 9

e a
3

Cholestan A/B trans B/C trans C/D trans Dy 5 (normal)

Coprostan A/B cis B/C trans C/D trans Dy 5 (allo)

M t s steroid th ng g p:
CH3 CH3 H HO H H HO HO H H CH3 CH3 H OH HO CH3

COOH

Cholesterol

Vitamin D3
HO

Acid cholic
HO

HO

HO

O HO

H O HO O

Testosteron

-Estradiol

Cortisol

39

4/18/2012

Cholesterol
CH3 CH3
10

H13

17

H
6

9 8 14 H

HO

Cholesterol

- C trong m t, d u gan c, no v c t s ng. - C vai tr quan tr ng trong hnh thnh c u trc t bo v kch thch t . - c chuyn ch b i LDL t i t bo v HDL v gan chuy n ha.

* Ph n ng mu c trng c a cholesterol: - Cholesterol/CHCl3 + H2SO4 mu (ph n ng Salkowski) - Cholesterol/CHCl3 + hh (CH3CO)2O/H2SO4 mu xanh l.

H 2, Pt Cr2O3 Zn-Hg/HCl

Cholesterol

Cholestanol

Cholestanon

Cholestan

Ergosterol
22

CH 3 CH3
8H 7 6

23

HO

Ergosterol

- L ti n vitamin D, s chuy n ha thnh vitamin D d i tc d ng c a nh sng.

40

4/18/2012

Vitamin D
- Chuy n ha calci v phosphor gip t o xng.

CH 3 CH3
8H 7 6

CH 3 HO

CH 3

as
5 8H

as
H CH 2

HO

Ergosterol

Pre-ergoscalcifeol
OH
22 23

Ergoscalcif erol (Vit D2)

22

CH 3

CH 3

23

HO

HO

Vitamin D3

Vitamin D4

Acid m t
- Do ti m t ti t ra, gip ch t bo th m c vo ru t.
21 18 12 22 23 20

CH3

19

CH3
2 3 1 10 5 4

11

13 14

17

COOH
16 15

9 6

8 7

Acid cholanic

Tn acid m t V tr nhm OH Acid cholic 3, 7, 12 Acid deoxycholic 3, 12 3 Acid lithocholic Acid chenodeoxycholic 3, 7 Acid hyodeoxycholic 3, 6

41

4/18/2012

Cc hormon
- Cc ch t do tuy n n i ti t t o ra, c cc tc d ng sinh h c khc nhau.
21 18

CH3
19

18

18 19

CH3 CH3

CH3

20

CH3

Khung estran

Khung androstan

Khung pregnan

Estrogen

Androgen

Progestagen Mineralocorticoid Glucocorticoid

OH
21

HO H

H OH

OH HO
11 17

O X

HO

HO

-estradiol

-estradiol

testosteron

X=H: mineralocorticoid X=OH: glucocorticoid

42