Reinvestigation of a synthesis of (R,S)-mevalonolactone

Abstract

An n.m.r. study of the reaction of 3-hydroxy-3-methylpentane-1,5-dioic acid (5) with excess of [²H₆]-acetic anhydride is described. It has shown that 3-hydroxy-3-methylpentane-1,5-dioic acid anhydride (2), previously described by Scott and Shishido ¹ as an intermediate in their synthesis of [3′-¹³C]mevalonolactone, is formed only transiently, along with 3-acetoxy-3-methylpentane-1,5-dioic acid (6). Both intermediates eventually give 3-acetoxy-3-methylpentane-1,5-dioic acid anhydride (3).

To obtain (R,S)-mevalonolactone, sodium borohydride reduction of 3-hydroxy-3-methylpentane-1,5-dioic acid anhydride (2), prepared from the diacid (5) and N,N-dicyclohexylcarbodi-imide, is shown to be better than reduction of 3-acetoxy-3-methylpentane-1,5-dioic acid anhydride (3).