Synthetic studies of mycalolide B, an actin-depolymerizing marine macrolide: construction of the tris-oxazole macrolactone using ring-closing metathesis

• Published in: Tetrahedron letters Vol. 51; no. 37; pp. 4882 - 4885
• Main Authors: Kita, Masaki, Watanabe, Hidekazu, Ishitsuka, Tomoya, Mogi, Yuzo, Kigoshi, Hideo
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.09.2010; Elsevier
• Subjects: Actin-depolymerizing compound; Chemistry; Chemistry, Organic; Physical Sciences; Ring-closing metathesis; Science & Technology; Synthesis of marine natural products; Tris-oxazole macrolide; Tris-oxazole macrolide; Synthesis of marine natural products; Actin-depolymerizing compound; Ring-closing metathesis; NUDIBRANCH HEXABRANCHUS-SANGUINEUS; CYTOTOXIC MACROLIDES; ULAPUALIDE; ABSOLUTE STEREOCHEMISTRY; KABIRAMIDE-C; ORIGIN; SPONGE; POTENT ANTITUMOR SUBSTANCE; CARBONYL ADDITION; CONGENERS APLYRONINE-B
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2010.07.046

Tris-oxazole macrolactone 2, a key intermediate of mycalolide B, was synthesized through the use of ring-closing metathesis (RCM). Tris-oxazole macrolactone 2, a key intermediate of mycalolide B ( 1), which has 13 stereogenic centres, was synthesized through the use of ring-closing metathesis (RCM). The E/ Z ratio of the RCM product 2 was reversed by the use of CH 2Cl 2 and toluene, whereas a cross-metathesis reaction yielded the C1–C35 long-chain compound 19 in a highly E-selective manner. Thus, the loss of flexibility in aliphatic carbon chains and the steric hinderance of β- and γ-substituents of the C20 olefin in the precursor 11 may affect the stereoselectivity in RCM reactions.