BIOMIMETIC SYNTHESIS OF THE PENTACYCLIC NUCLEUS OF PTILOMYCALIN-A

The methyl ester of the pentacyclic nucleus of ptilomycalin A (9) has been prepared by an efficient, convergent, biogenetic, 14-step route. The key steps involve the conversion of acyclic bis enone 39 to 9 in four steps. Michael addition of O-methylisourea to 39 afforded 52% of a mixture of isoureas 40 and 41, which were both converted to 72% of tricyclic aminals 42 and 43 by ammonolysis. Deprotection of the silyl ethers with HF and cyclization with Et3N in MeOH afforded 9 (almost-equal-to 34% from 42) and the diastereomer 45 with an equatorial methyl ester group (almost-equal-to 26% from 42).