Fundamentals of Medicinal Chemistry

Table 10.4 Examples of reactions used to reverse FGIs. R can be both an aromatic and an aliphatic

residue but Ar is only an aromatic residue

Alkenes:By elimination of alcohols and halides.

Aldehydes and ketones: By oxidation of the appropriate alcohol.

Amines:

Useful one carbon additions to aromatic ring systems:

RNH 2 + OC

R

R^1

C

R

R^1 R^1

RN

R

RNH−CH

OH−

H

Br

C

R

R^1

OH

CHO

R

R^1

CH−OH O

Secondary alcohol Ketone

Oxidation

Ar−H Ar−CH 2 Cl

HCHO/HCl/ZnCl 2

Chloromethylation

Ar−ΟΗ

Phenols

Ar

CHCl 3 /OH−

Riemer−Tiemann

Condensation Reduction

Reduction

R−NO 2 R−NH 2 RCONHR^1 RCH 2 NHR^1

Reduction

RCH 2 OH RCHO

Oxidation

Primary alcohol Aldehyde

HO

H

H+

10.4 Questions

(1) Explain the meaning of the terms (i) linear, (ii) convergent and (iii) partial

synthetic pathways.

(2) Outline the practical considerations that need to be taken into account when

selecting reactions for use in a synthetic pathway.

(3) Describe the use of catalysts in asymmetric synthesis.

(4) What is a chiral auxiliary? Suggest a feasible stereospecific synthesis for

2R-methylhexanoic acid starting from S-()-proline and propanoic

anhydride.

220 AN INTRODUCTION TO LEAD AND ANALOGUE SYNTHESES