Stereochemistry of the double band saturation in the formation in baker's yeast of 4-(4-hydroxyphenyl)-2-butanone (Raspberry ketone)

Yeast extract-mediated reduction of 4-(4-hydroxyphenyl)-but-3-en-2-one 3 to raspberry ketone I occurs with transfer beta to the carbonyl group of H-R from NADPH and of an hydrogen atom from the solvent at alpha position, as indicated by experiments with (4R) and (4S) [4-H-2]-NADPH and with deuterated solvent. The same extract converts 3 in 1 in the presence of NADH, but much less efficiently. In this latter case H-S and not H-R is transferred from the reduced cofactor to position 4 of 1. Horse liver alcohol dehydrogenase-mediated reduction of 1, bearing deuterium labelling at positions 1, 3 and 4 and obtained from 3 using the whole-cell system in the presence of D2O, gave an S carbinol possessing 0.95 ee, shown by H-2 NMR studies onto the diacetate 7 to contain an excess of the (3S,4S) diastereoisomer, thus suggesting a prevalent beta re-face,syn addition of hydrogen across the double bond of 3 in the whole-cell mediated conversion into 1.