Totalsynthese von natürlichem α‐Tocopherol. 1. Mitteilung. Herstellung bifunktioneller, optisch aktiver Synthesebausteine für die Seitenkette mit Hilfe mikrobiologischer Umwandlungen

Abstract

Total Synthesis of Natural α‐Tocopherol. I. Preparation of Bifunctional Optically Active Precursors for the Synthesis of the Side Chain by Means of Microbiological Transformations Our concept for a new total synthesis of natural α‐tocopherol includes the synthesis of a corresponding (3 R , 7 R )‐configurated C 15 side chain to be built up by using twice an optically active C 5 unit together with an achiral C 5 end part. ( S )‐3‐methyl‐γ‐butyrolactone ( 11 ) and ( S )‐2‐methyl‐γ‐butyrolactone ( 9 ) represent suitable bifunctional C 5 ‐precursors for this purpose. These two key compounds have been prepared by fermentative transformation including the enantioselective hydrogenation of the double bond of ethyl‐4, 4‐dimethoxy‐3‐methylcrotonate ( 5 ) by bakers yeast (yielding 11 after ester hydrolysis and cyclization of the fermentation product) and ( E )‐3‐(1′, 3′‐dioxolan‐2′‐yl)‐2‐buten‐1‐ol ( 8 ) by the fungus Geotrichum candidum (yielding directly 9 ).