Stereochemistry of the double bond saturation in the formation in Baker's yeast of 4-(4-hydroxyphenyl)-2-butanone (raspberry ketone)

Article abstract of DOI:10.1016/S0040-4020(96)00066-X

Yeast extract-mediated reduction of 4-(4-hydroxyphenyl)-but-3-en-2-one 3 to raspberry ketone 1 occurs with transfer β to the carbonyl group of H(R) from NADPH and of an hydrogen atom from the solvent at α position, as indicated by experiments with (4R) and (4S) [4-²H]-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 ²H NMR studies onto the diacetate 7 to contain an excess of the (3S,4S) diastereoisomer, thus suggesting a prevalent β re-face,syn addition of hydrogen across the double bond of 3 in the whole-cell mediated conversion into 1.