METHYL (S)-LACTATE AS A CHIRAL AUXILIARY IN THE ASYMMETRIC-SYNTHESIS OF BAO-GONG-TENG-A

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 59 as a major product. The crude cycloadduct was reduced by catalytic hydrogenation to produce 6 in 61% yield. The ketone 6 was reduced with LiAl(OtBu)(3)H to give exo alcohol 7b in 62% 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 91% yield for the three steps. The acid 13 was converted to the ketone 14 in 82% yield via the acid chloride. Baeyer-Villiger oxidation converted 14 to 15 in 52% yield. Optically pure Bao Gong Teng A was obtained in 9% overall yield by the removal of both the Boc and the TBDMS groups using 1% HCl-EtOH.