Total synthesis of (+)-cephalostatin 1 and dihydrocephalostatin 1

Sudhakarrao Bhandaru, Purdue University

Abstract

Reported herein are the first total syntheses of (+)-Cephalostatin 1 and Dihydrocephalostatin 1. Pertinent highlights of the above stated syntheses include (1) the proximal functionalization of the C-18 methyl group in alcohol 2.19 via Meystre's hypoiodite method (2) the regioselective rhodium-carbenoid mediated O-H insertion reaction of ethyldiazophosphonate 2.50 into the primary neopentiyl hydroxyl group of triol 2.18 (3) the regiospecific intramolecular Wadsworth-Emmons reaction in the diketophosphonate ester 2.47 to exclusively afford the six-membered dihydropyran ester 2.49 (4) establishment of the stereochemistry of spiroketals 3.11, 3.12$\alpha$ and 3.12$\beta$, obtained from the acid-catalyzed spirocyclization reaction of 3.10, using state-of-the-art two-dimensional NMR methods and subsequent confirmation of the NMR assigned configurations via X-ray crystallography (5) conversion of the South spiroketal 3.20, of Dihydrocephalostatin 1 (1.33) into the South spiroketal 3.34, of Cephalostatin 1 (1.1) and (6) unsymmetrical coupling of the South $\alpha$-azidoketones 2.11 and 2.12 with the North $\alpha$-aminomethoxime 2.13 to complete the syntheses of Dihydrocephalostatin 1 (1.33) and (+)-Cephalostatin 1 (1.1), respectively.

Degree

Ph.D.

Advisors

Fuchs, Purdue University.

Subject Area

Organic chemistry

COinS