Rearrangement Approaches to Cyclic Skeletons. 6. Total Synthesis of (+/-)-Ptilocaulin on the Basis of Formal Bridgehead Substitution and Photochemical Acyl Migration of a Bicyclonon-6-en-2-one System

Article abstract of DOI:10.1021/jo00251a004

The total synthesis of (+/-)-ptilocaulin (1), the antimicrobial and cytotoxic guanidine-containing natural product, starting from 1-methoxybicyclo<3.2.2>non-6-en-2-one (3) is reported.The 3-endo-methyl derivative of 3, 4, was obtained selectively under kinetically controlled conditions.The bridgehead methoxy group of 4 was replaced by a butyl group, with inversion of absolute configurations, upon successive treatment with butyllithium and p-toluenesulfonic acid in benzene.The thus obtained 1-butyl-exo-8-methylbicyclo<3.2.2>non-6-en-2-one was transformedpchotochemically into the <5,6> fused-ring ketone, 4-butyl-exo-3-methylbicyclo<4.3.0>non-4-en-7-one (7).Transposition of the carbonyl group and the olefin of 7 to give a mixture of exo-3- and endo-3-butyl-4-exo-methylbicyclo<4.3.0>non-9-en-2-ones was achieved in a six-step seqence.From these conjugated ketons, (+/-)-ptilocaulin was derived by treatment with guanidine.