Synthesis of bridged thiazolium salts as models for thiamin

Abstract

Bridged thiazolium salts 16b and c have been synthesized in a short procedure starting with ω-amino acids. Condensation with carbon disulfide and α-chloro ketone 19 provided thiazole-2(3H)-thiones 14b and c and the bridge was then formed by standard macrolactonization procedures. Oxidation of the thiones with hydrogen peroxide then gave the thiazolium salts. The same cyclization procedures failed to yield the shorter bridged compound 15a but gave the cyclic dimer and trimer. Starting with protected lysine derivatives 31b and c, thiazole-2(3H)-thiones 36b and c were obtained. In both cases the cyclization reaction yielded two separable atropisomers depending on which side of the ring the bridge was formed. The catalytic reactions of thiazolium salts 16b and c were compared with unbridged analogues and it was found that, whereas the longer bridged one behaved normally, the shorter bridged salt was unable to catalyse the benzoin condensation. A novel 2-benzoyl-2,3-dihydrothiazole 44 was isolated from this reaction mixture.