Total synthesis of the polyether antibiotic X-206

Article abstract of DOI:10.1021/ja00216a026

A convergent asymmetric synthesis of the polyether antibiotic X-206 has been achieved through the synthesis and coupling of the C₁-C₁₆- and C₁₇-C₃₇ synthons 16 and 17, respectively. All absolute stereochemical relationships within the molecule were controlled by application of recent methodological advances in asymmetric synthesis. In the synthesis of subunit 16, both the alkylation and aldol reactions of chiral imide-derived enolates were utilized to establish the five stereogenic centers at C₂-C₄ and C₉-C₁₀, while the stereochemistry at C₁₄ was indirectly controlled by the Sharpless asymmetric epoxidation. The C₇ and C₁₁ stereocenters, which are situated at the two assemblage points for 16, were established through internal asymmetric induction. The synthesis of the more complex C₁₇-C₃₇ subunit 17 followed a similar strategy for absolute stereocontrol. Chiral enolate methodology was employed to define the stereogenic centers at C₁₈, C₂₂, and C₂₃ while asymmetric epoxidation was used to create the oxygen-bearing centers at C₃₀-C₃₁ and C₃₄-C₃₅. The remaining three stereogenic centers at C₂₀, C₂₆, and C₂₈ were controlled by internal asymmetric induction. The successful construction of this synthon relied upon the development of an efficient assemblage reaction in which three fragments comprising the entire carbon framework of 17 were united in a single operation. The final coupling of the two halves was achieved by a nonstereoselective aldol reaction. In supporting studies, the selective manipulation and degradation of the natural product were also investigated.