ChemInform Abstract: A Short Large Scale Synthesis of (.+-.)-Sarkomycin Esters.

Abstract

Abstract : (k) Sarkomycin ethyl ester has been prepared in four steps from ethyl actylate. We have previously described the substitution of a-functionnal acrylic esters by Grignard reagents in the presence of a catalytic amount of copper (I) (1). This reaction can be applied to lithium enolates (ester or ketone). It gives then rise to new a-substituted functional actylates which are of great interest for the synthesis of biological active compounds (a-methylene &valerolactone, (+)-sarkomycin). CH,OAc flc”” =(COOEt FOOEt v 2.5% Cu(l), -7O”C, THF-Et20 - CH20Ac + COOEt Li-CH,-COOt-Bu THF-Et20, -80°C -CH2 Yield 83% COOEt ===c CH,-CH,-COO,-BU 1 Yield 66% A recent publication (2) on the synthesis of (+) sarkomycin including the same phosphonate 3 as a key intermediate prompts us to describe here our results. Many other preparations of (k) sarkomycm (or its esters) have been reported by mutli step syntheses (2, 3) with low overall yields. We report here a very short, large scale and improved synthesls of two (&) sarkomycin esters using low cost products and methodology. a-Methylene glutaric acid diester 1 can be included in a very short