Multigram Synthesis of Mevalonolactone-d9 and Its Application to Stereochemical Analysis by 1H NMR of the Saturation Reaction in the Biosynthesis of the 2,3-Di-O-phytanyl-sn-glycerol Core of the Archaeal Membrane Lipid

Abstract

A synthetic method for (RS)-mevalonolactone-d9 (8) was developed starting from deuterated dimethoxyphenylacetone and trimethyl phosphonoacetate. The overall yield of 8 was 33% in seven steps on a multigram scale. Synthesized mevalonolactone-d9 was applied to biosynthetic studies of the archaeal core membrane lipid 2,3-di-O-phytanyl-sn-glycerol. Mevalonolactone-d9 was highly incorporated into the phytanyl chains of the archaeal lipid, and the total enrichment was approximated to be as high as 70%. The mevalonate pathway is clearly responsible for the biosynthesis of the phytanyl chains of the core lipid in the archaeal membrane. Further, saturation of the geranylgeranyl group to the phytanyl group was shown to take place through the addition of hydrogen in a syn manner by analyzing the behavior of protium on the heavily deuterated archaeal lipid by 1H NMR spectroscopy.