Total synthesis of the CP-molecules (CP-263,114 and CP-225,917, phomoidrides B and A). 3. Completion and synthesis of advanced analogues

K C Nicolaou; Y-L Zhong; P S Baran; J Jung; H-S Choi; W H Yoon

doi:10.1021/ja0120126

Total synthesis of the CP-molecules (CP-263,114 and CP-225,917, phomoidrides B and A). 3. Completion and synthesis of advanced analogues

J Am Chem Soc. 2002 Mar 13;124(10):2202-11. doi: 10.1021/ja0120126.

Authors

K C Nicolaou¹, Y-L Zhong, P S Baran, J Jung, H-S Choi, W H Yoon

Affiliation

¹ Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.

PMID: 11878974
DOI: 10.1021/ja0120126

Abstract

The completion of the total syntheses of the CP-molecules is reported. Several strategies and tactics, including the use of amide-based protecting groups for the homologated C-29 carboxylic acid and the use of an internal pyran protecting group scheme, are discussed. The endeavors leading to the design of new methods for the homologation of hindered aldehydes and to the isolation of a polycyclic byproduct (23), which inspired the development of a new series of reactions based on iodine(V) reagents, are described. In addition, the discovery and development of the LiOH-mediated conversion of CP-263,114 (1) to CP-225,917 (2) is described, and a mechanistic rationale is presented. Finally, a synthetic route to complex analogues of the CP-molecules harboring a maleimide moiety in place of the maleic anhydride is presented.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Enzyme Inhibitors / chemical synthesis*
Maleic Anhydrides / chemical synthesis*
Stereoisomerism

Substances

CP 225917
CP 263114
Enzyme Inhibitors
Maleic Anhydrides