Zum stereochemischen Verlauf der Biosynthese von 2-Oxo-pantolacton: Synthese von stereospezifisch indiziertem Pantolacton aus Aepfelsaeure

Article abstract of DOI:10.1002/hlca.19820650136

(+)-Pantolactone (13) has been synthesized from (-)-(S)-dimethyl malate (7) in 40percent yield in a short sequence involving double alkylation (7 -> 10 -> 11), selective hydrolysis (11 -> 12) and subsequent reduction (12 -> 13).Through variation of the alkylating agents and preparation of the two diastereomeric 3-ethyl-3-methyl malates 14 and 15 it was possible to show that the diastereoselectivity of the second alkylation step is brought about by preferential attack from the Re-face of the critical enolate (9, see also Scheme 1).This knowledge, in turn, has been exploited for the synthesis of a sample of pantolactone specifically enriched with 13C in its Si-methyl group.Analysis of the 13C-NMR. spectrum of this sample together with the results of biosynthetic experiments previously reported by Aberhart demonstrates that the biological hydroxymethylation of 2-oxoisovaleric acid (3) to 2-oxopantoic acid (4), an important step in the biosynthesis of pantothenic acid, takes place in a retention mode (cf.Scheme 2).