Investigations into a Biomimetic Approach toward CP-225,917 and CP-263,114

Abstract

A biosynthesis of the structurally complex nonadride CP-225,917 (1) is outlined. A key step in this proposal is the dimerization of a C(16) anhydride derived from the condensation of lauric acid and oxaloacetic acid. An important element of this step is a templating effect imposed by two thioester linkages, reminiscent of a polyketide or fatty acid synthase pathway. On the basis of this principle, the dimerization of two C(11) anhydrides, templated by a 1,n-diol tether, leading to the core structure of CP-225,917 and CP-263,114 was investigated.

Diastereoselective Total Synthesis of (±)‐Schindilactone A

“…Cyclopropanation of 9 with dibromocarbene [14] provided 10, which was subsequently treated with AgClO 4 [15] in acetone to give vinyl bromide 11 in 82 % yield after two steps. After palladium-catalyzed coupling of 11 with (1-tert-butoxyvinyloxy)(tert-butyl)dimethylsilane, [16] ketoester 12 was obtained in 85 % yield. The structure of 12 was confirmed by X-ray crystallographic analysis.…”

Diastereoselective Total Synthesis of (±)‐Schindilactone A

“…Cyclopropanation of 9 with dibromocarbene14 provided 10 , which was subsequently treated with AgClO 4 15 in acetone to give vinyl bromide 11 in 82 % yield after two steps. After palladium‐catalyzed coupling of 11 with (1‐ tert ‐ butoxyvinyloxy)( tert ‐butyl)dimethylsilane,16 ketoester 12 was obtained in 85 % yield. The structure of 12 was confirmed by X‐ray crystallographic analysis 31…”

Elucidation of the Biosynthetic Pathway Leading to the Complex Nonadride Phomoidride B

“…15,16 This project was initiated by Mike Corbett and later joined by Fabio Agnelli. Mike and Fabio examined a variety of substrates for the key cyclization.…”