Abstract
It is theoretically possible, by utilizing biological stereoselectivities toward meso or prochiral molecules, to transform the starting material into the optically active compound quan titatively. To develop this useful methodology for asymmetric syntheses, we attempted a microbiological transformation of a symmetrical diketone, 8a-methyl-cis-2, 7-decalindione [4], into a chiral ketol. Incubation of [4] with Rhodotorula rubra gave a mixture of two diastereomeric ketols in a ratio of 4:1, Acetylation of the metabolite followed by chromatography afforded keto acetates [6] and [8] which were hydrolyzed to furnish (+)-ketol 5 (54% yield, mp 67-68°C, [α]D25 +12.3°, 88% optical purity) as a major product and (-)-ketol [7] (13%yield, mp 99-100°C, [α]D25 -45.4°, 93% optical purity) as a minor product. The chemical conversion of (-)-ketol [7] to (+)-6-methyl-4-t wistanone [10] with (R)-framework (mp 133-135°C, [α]22D, +300°), via keto mesylate [9], gave information on the stereochemistry of (-)-ketol [7] as being (4aR, 7S, 8aS)-configuration. For inversion of the configuration at C-7, (+)-ketol [5] was converted to keto tosylate [16] and was treated with KNO2, in DMSO to afford (+)-ketol ([α]D20 +43.1°) which was found to be an enantiomer of (-)-ketol [7]. Thus, the absolute configuration of (+)ketol [5] was determined as being (4aS, 7S, 8aR). These results clearly show that R. rubra prefe rentially catches the pro-S group of two enantiotopic carbonyl groups on the diketone [4], and the hydrogen attack occurs from the Re-face of the carbonyl plane. The Wolff-Kishner re duction of (+)-ketone [10] gave (+)-1-methylwistane [11] (mp 113-114°C, [α]D22 +399°, 93% optical purity). Thus, a. microbiological reduction cou pled with a chemical conversion provided a convenient synthetic route to a cage-shaped hydrocarbon [11] with high optical purity.
