New synthetic methods in rotenoid chemistry: [7′-13C]- and [7′-14C]-(–)-rotenone and (±)-isorotenone

Abstract

A reconstructive circuit for ¹³C- and ¹⁴C-labelling of the 7′-methylene group of (–)-rotenone is described. It involves blocking the enolisable 12a-site with a trimethylsilyloxy-group, followed by removal and reintroduction of the methylene, and elision of the blocking group : the radiochemical yield is 19%. Consequences of failure to block the 12a-site in reactions with ylides are illustrated by reactions of (–)-Isorotenone, (–)-rotenone, and (–)-rotenone 7′-norketone (1f) with dimethyloxosulphonium methylide, which leads to C-seco-cyclopropyl ketones.

A new rotenoid synthesis from 2,2′-dihydroxydeoxybenzoins which produces the B/C-ring system directly at the correct oxidation level is described. This involves blocking of the two unwanted nucleophilic sites by ring formation. The O-methylene aldehyde is concealed as an allyl group for introduction purposes, and after removal of the blocking ring, development of the aldehyde, and base-catalysed cyclisation, (±)-isorotenone (used as the model rotenoid) was obtained. Since 2,2′-dihydroxydeoxybenzoins are readily made by degradation of natural rotenoids, the method can be used for reconstructive isotopic labelling at C-6 and C-6a.