Acronycine epoxide

Acronycine epoxide 61 was isolated in minute amounts from Sarcomelicope agyrophylla Guill. and from Sarcomelicope simplicifolia (Endl.) Hartley ssp. neo-scotica (P.S. Green) Hartley (68). This compound should be considered as a biogenetic intermediate between acronycine itself and the cis and frans-dihydrodiols 48. and in Sarcomelicope species. It is a highly unstable compound whose reactivity most probably explains the difficulties encountered by us (72) and by others (73, 74) in attempts towards its synthesis. Reisch et al. finally succeeded in synthesizing in 14 % yield by treatment of acronycine with dimethyldioxirane in the presence of potassium carbonate (75). 

The high reactivity of acronycine epoxide f6n led us to speculate that this compound should be the active metabolite of acronycine in vivo and that it should be responsible for the alkylation of nucleophilic targets within the tumor cell (68). This hypothesis was in good agreement with the mode of action previously established (76) for the insecticidal chromenes precocenes I (62) and II (63 ). whose structures share a dimethylbenzopyran unit in common with acronycine (i). 

The great chemical instability of acronycine epoxide, for instance its fast reaction with water to yield the corresponding diols (72), exclude its possible use as an anticancer agent. This is the reason why we synthesized a series of ci s-l,2-dihydroxy-l,2-dihydroacronycine and c/s-l,2-dihydroxy-... 

Acronycine epoxide C20H19NO4 MW 337 mp yellow foam spectral data 255 source 255... 

In order to ensure that the reactivity of cjj-1,2-dihydroxy-1,2-dihydroacronycine diesters towards nucleophilic agents was similar to that of acronycine and precocene epoxides, the diester was reacted with benzylmercaptan (2i) in acidic medium. The cis and trans adducts 7 and with the sulfur atom linked to the benzylic position of the pyranyl ring were obtained in almost quantitative yield under these conditions (58). 

---