A Bidirectional Approach to the Synthesis of Polypropionates: Synthesis of C1–C13 Fragment of Zincophorin and Related Isomers

• Published in: Journal of organic chemistry 2011-10, Vol.76 (19), p.7654-7676
• Main Authors: Mochirian, Philippe, Godin, François, Katsoulis, Ioannis, Fontaine, Isabelle, Brazeau, Jean-François, Guindon, Yvan
• Format: Article
• Language: English
• Subjects: Aldehydes - chemistry; Chemistry; Chemistry Techniques, Synthetic - methods; Coordination compounds; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Hydrogen - chemistry; Inorganic chemistry and origins of life; Organic chemistry; Polymers - chemical synthesis; Polymers - chemistry; Preparations and properties; Propionates - chemical synthesis; Propionates - chemistry; Stereoisomerism
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo2013884

The structure–activity study of a bioactive natural product containing polypropionate subunits requires that its stereoisomers also be evaluated. Therefore, a general approach to synthesize these motifs is necessary. We describe herein the synthesis of the C1–C13 polypropionate subunit of zincophorin and isomers thereof using a two-reaction sequence: an aldol reaction using a mixture of tetrasubstituted enoxysilanes and a hydrogen-transfer reaction, both under Lewis acid control. Selection of the appropriate Lewis acid dictates the stereochemical outcome of these reactions. From a tactical standpoint, this study shows how a polypropionate sequence can be read and constructed in two directions, either the east–west or the west–east approaches. The choice of the optimal route is influenced by the number of complexation sites that can interfere in the aldol step under bidentate Lewis acid control.