A total synthesis of allamcin. An approach to antileukaemic iridoid lactones and formal syntheses of plumericin and allamandin

Abstract

A total synthesis of the iridoid lactone (±)-allamcin (3) found in Allamanda neriifolia is described. Starting from the readily available bicyclo[3.3.0]octenone (10), the synthesis uses a strategy based on: (i) elaboration of the key acetoxy-aldehyde intermediate (9) through epoxidative rearrangement of the enol acetate (71) derived from (10)via the unsaturated aldehyde (57), (ii) fusion of the β-oxy-γ-butyrolactone ring system on to (9) using the dianion (20) derived from 2-phenylthiobutanoic acid, (iii) chemo-selective vic-bishydroxylation of the ring B carbon-to-carbon double bond in (75), using osmium tetraoxide, leading to (76), (iv)in situ oxidation and elimination of phenylsulphenic acid from (76) producing the (E)-ethylidenefuranone (78), and (v) oxidative-cleavage and cyclisation from the 1,2-diol (78) in the presence of sodium metaperiodate. Allamcin was also produced when the allylic transposed intermediate (84) derived from compound (83)(MeOH–K₂CO₃) was treated with periodic acid. Since allamcin has previously been converted into plumericin (4) and allamandin (5), the synthesis of compound (3) also constitutes formal syntheses of (±)-(4) and (±)-(5).