Helvetica Chimica Acta · 1982 · 56 citations · 19 references
Natural SciencesBiochemistryChemistryBiocatalysisNatural Product BiosynthesisOrganic ChemistryOrganic SynthesisRetrosynthetic AnalysisSecondary Metabolite BiosynthesisAlkylation ProcessesAlkylation ReactionsHydrolysis
Abstract (+)‐Pantolactone 1 ( 13 ) has been synthesized from (−)‐( S )‐dimethyl malate ( 7 ) in 40% 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 13 C in its Si ‐methyl group. Analysis of the 13 C‐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 ( of. Scheme 2 ).
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