紫杉醇手性側(cè)鏈的合成

紫杉醇手性側(cè)鏈的不對(duì)稱合成師少宇

2010、9、

12Best

wishes

to

our

laboratory紫杉醇（taxol）:短葉紅豆衫樹皮中分離得到的具有很強(qiáng)抗腫瘤活性化合物[1]，迄今3種最重要植物來(lái)源抗癌藥之一。全合成半合成Holton；Nicolaeu1994[2]人工合成植物提取紫杉醇手性側(cè)鏈的不對(duì)稱合成方法12341由?-苯基環(huán)氧丙酸酯合成由?-內(nèi)酰胺合成CANSeveral

classic

replacementH

to

F

replacement-OH

to

-NH2

or

–SHHalogen

replacementsRing

replacements-COOH

replacements1.

H

to

F

replacementFluorine

has

similar

size

with

hydrogenmost

electronegative

halogen,

C-F

bond

very

stableIdeal

replacement

to

study

the

effect

of

electronegativitchange

.Thus,

F

(or

other

halogens

when

size

is

not

critical)

are

frequently

place

on

easily

oxidized

aromatics,

Methyl

groups

often

substituted

by

CF32.

-OH

to

-NH2

or

–SH(also

C=O

to

C=NH

or

C=S)Replacement

of

-OH

with

-NH2

can

stabilize

a

differenttautomer,

especially

in

the

case

of

heterocyclic

systemsExamplesExamples3.

Halogen

replacements

-CN

and

-CF3

may

be

used

as

alternative

electron-withdrawing

groups

instead

of

halogens.

The

two

groups

have

comparable

effects

on

electronics,but

-CN

will

increase

the

overall

hydrophilicity.Ring

replacements-COOH

replacementsCarboxyl

group

may

be

replaced

in

order

to

alteracidity,

or

modify

lipophilicity

without

affecting

pKTetrazoles

have

comparable

pKa

with

carboxylic

acids,

butgreater

lipophilicity

By

changing

ethyl

ester

with

a

bioisostere

oxazolemoiety,

151

is

metabolically

stable

against

esterases,maintains

the

selectivity

and

shows

increased

CDK2inhibitory

potency

as

well

as

potent

antiproliferativeactivity

in

cancer

cell

lines161:

dopamine

D3

inhibitor162:

maintained

affinity

for

the

dopamine

D3

receptorand

introduced

modest

selectivity

over

the

dopamineD2

receptor.163:

exhibits

dopamine

D3

and

dopamine

D4

bindingaffinities

comparable

to

those

of

the

atypicalneuroleptics

sultopride

and

clozapine.IndomethacinTetrazole

derivativeAnti-arthritis

drug-

Non

steroidal

anti-inflammatory

drug

–

reduces

fever,

pain,stiffness,

delays

premature

labour

&

other

usesTetrazoles

are

used

in

drugs

as

replacements

for

CO2H

by

change

the

pKa.Preparation

of

tetrazolesinspiration