Formation of the S-unsubstituted, O-methyl acyl tetronic acid nucleus found in tetronasin (1) has been achieved by the direct acylation of a 3-stannyl tetronate with a variety of acid chlorides in the presence of a palladium catalyst. Funherjknctionalizanon of the tin tetronate at C-5 prior ro acylation leads to the synthesis of the mouhi me&o&e (*) a?methyl carolinic acid (12) and the 5-methylene tetronate nucleus found in tetronomycin (2).
Tetronasin (1)1 and tetxonomycin (2)2 are structurally-related polyether ionophore antibiotics recently isolated from the fermentation of two closely-related Streptomyces species. tetronasin 1 tetronomycin 2
As part of a synthetic programme towards (1) we required a method for the preparation of S-unsubstituted, 3-acyl tetronic acids (3). Although there have been several reported approaches to this system involving the cyclization of u-substituted derivatives of ethyl glycollate3. the simplest approach to (3) employs the direct C-3 acylation of a suitable tetronic acid derivative. Several methods have been devised to address this problem4, however they all suffer from harsh reaction conditions, lack of generality or poor yields. The direct acylation of O-methyl tetronic acids lithiated at C-3 has been accomplished5 but C-5 unsubstituted substrates undergo preferential deprotonation6 and our attempts to acylate the dianion (4) led to a mixture of products.