Organic Chemistry of Drug Synthesis. Volume 7

make up polysaccharide can be viewed as acetals of aldehydes. These func-
tions on endogenous peptides and saccharides do occasionally interact
chemically to form cross-links. Accumulation of cross-linked proteins
with age is believed to lead to stiffening of tissues. Some of these processes
may go as far as to result in pathologic changes. A structurally very simple
thiazolium salt has shown activity in reversing such changes by breaking
cross-links. The compound is probably prepared by reaction of
dimethylthiazole ( 156 ) with phenacyl chloride ( 157 ). The productalageb-
rium chloride( 158 ) is said to show promise in treating effects traceable to
loss of tissue elasticity.

S

NH

+

O

Cl

156 157

S

O

Cl+ N+

158

The “glitazones” comprise a large series of antidiabetic compounds that
were introduced about a decade ago. The original hypoglycemic drugs
used for control of Type 2 diabetes were marked by the presence of a sul-
fonyurea pharmacophore. This function is replaced by a thiazolidinedione
group in the more recent glitazones. The synthesis of a very recent drug
candidate in this group begins with reduction of the carboxylic acid in
the naphthol ( 159 ) with diborane. The resulting carbinol is oxidized back

HO

CO 2 H

159

1. BH 3
   2. MnO 2 HO

CH=O

160

NH

S O

O

NH

S O

HO O

161

H 2

NH

S O

HO O

162

F

Cl

NH

S O

O

163

F

O

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