Methyl (S)-Lactate as a Chiral Auxiliary in the Asymmetric Synthesis of Bao Gong Teng A

Article abstract of DOI:10.1021/jo00129a053

The asymmetric synthesis of Bao Gong Teng A, (-)-1, a natural product that shows strong antiglaucoma properties, is described.The synthesis begins with an asymmetric 1,3-dipolar cycloaddition of the acrylate of methyl (S)-lactate to the betaine of N-benzyl-3-hydroxypyridinium chloride giving cycloadduct 5a as a major product.The crude cycloadduct was reduced by catalytic hydrogenation to produce 6 in 61percent yield.The ketone 6 was reduced with LiAl(OtBu)3H to give exo alcohol 7b in 62percent yield.Protection of the alcohol group followed by replacement of the benzyl group on the nitrogen with a Boc group gave 12, which was then hydrolyzed to the acid 13 in 91percent yield for the three steps.The acid 13 was converted to the ketone 14 in 82percent yield via the acid chloride.Baeyer-Villiger oxidation converted 14 to 15 in 52percent yield.Optically pure Bao Gong Teng A was obtained in 9percent overall yield by the removal of both the Boc and the TBDMS groups using 1percent HCl - EtOH.