A simple, efficient synthesis of 2-(l,2-dithiolan-3-yl)aeetic acid from Meldrum's acid, acrolein and thioacetic acid is described. The isopropyldene 2,4-b/s(acetylthio)butane-l, l-dicarboxylate formed in the threecomponent, single container process, can be methanolized to the corresponding dimethyl ester and then hydrolyzed, oxidized to the disulfide and decarboxylated to 2-(l,2-dithiolan-3-yl)acetic acid. The acid can be convened by conventional reagents into a variety of amide derivatives. Β© 1997 Elsevier Science Ltd. c~-Lipoamide is recognized as an important factor in a number of biochemical processes) One key role for this cofactor is in the transformation of pyruvic acid to acetyl CoA in the cocarboxylase complex where, attached to a lysine, it transfers the acetyl function from thiamine to CoASH. 2 The cofactor plays a major role in a variety of other oxidation-reduction enzyme structures. 3-5 The easy availability of a variety of analogs of lipoamide might not only provide insight into a further understanding of its role in metabolism but such materials and derivatives also have the potential to serve as models of the biochemical events, metabolic inhibitors and antagonists. In a wholly different area, materials of this type are becoming increasingly important as the attachment group for tethering enzymes, antibodies and other bioprobes to gold surfaces. 6
This potential to construct a variety of analogs having shorter or less flexible or more functionalized tethering arms between the acid or amide functional group and the disulfide ring came about from our interest in extrapolating the Michael addition chemistry ofthiols to Meldrum's acid derivatives. 7