Total Synthesis of the CP-Molecules (CP-263,114 and CP-225,917, Phomoidrides B and A). 2. Model Studies for the Construction of Key Structural Elements and First-Generation Strategy

• Published in: Journal of the American Chemical Society 2002-03, Vol.124 (10), p.2190-2201
• Main Authors: Nicolaou, K. C, Baran, P. S, Zhong, Y.-L, Fong, K. C, Choi, H.-S
• Format: Article
• Language: English
• Subjects: Chemistry; Enzyme Inhibitors - chemical synthesis; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Maleic Anhydrides - chemical synthesis; Models, Molecular; Organic chemistry; Preparations and properties; Stereoisomerism
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja012011d

Crucial model synthetic and mechanistic studies directed toward the development of methodology for the construction of the maleic anhydride moiety of the CP-molecules are described. Studies directed toward the stereoselective attachment of the upper side chain, culminating in the discovery of long-range stereochemical control, are also discussed. In addition, a first-generation strategy toward the CP-molecules, establishing key intermediate 5 as a “beachhead” from which all future operations would diverge, is also presented. Although this first-generation strategy failed to yield the target molecules, the endeavor laid the important groundwork for the next-generation drives toward the CP-molecules.