Total Synthesis of Swinholide A and Hemiswinholide A

Lithistid Sponges: Star Performers or Hosts to the Stars

“…Of these compounds, swinholide A (9) was shown to be the most cytotoxic [22] and has, therefore, been the target of both conformational [23] and synthetic studies that culminated in two excellent total syntheses. [24,25] The X-ray structure of discodermolide (12), an immunosuppressive and cytotoxic agent from Discodermia dissoluta, revealed a novel ªpolypropionateº structure. [26] Owing to its unusual and potentially useful biological profile, which includes the ability to stabilize microtubules more potently than taxol, [27] and the real or perceived difficulty in obtaining large supplies of the drug from natural sources, discodermolide (12) has become a popular target for synthetic programs.…”

Use of chiral auxiliaries in the asymmetric synthesis of biologically active compounds: A review

“…Initially, its structure was improperly characterized as a 22‐membered monomeric macrolide. However, in 1990, Kitagawa et al elucidated the dimeric nature of swinholide A, making appropriate corrections for preliminary structural elucidation, and determined its stereochemistry using mass spectroscopy and X‐ray crystallography . Swinholide A is composed of a C 2 ‐symmetrical 44‐membered dimeric dilactone skeleton, two conjugated diene systems, two trisubstituted pyran systems, and two disubstituted dihydropyran systems.…”

“…For example, it exhibited IC 50 values of 0.03 μg/mL for L1210 cells and 0.04 μg/mL for KB cells. In addition, swinholide A has antifungal activity . Its symmetrical and highly oxygenated structure is a striking feature and appears to be essential for its biological activities …”

Lessons learned from macrolide synthesis

“…The final macrolactonization had to be performed without jeopardizing the ester function already present. First, the TBS group was removed, and then the methyl ester was hydrolyzed with barium hydroxyde in methanol 40 to generate seco acid 99 , which was macrolactonized under Yamaguchi conditions to furnish 100 . Reoxidation of the free 9‐OH groups to the ketones and global deprotection with dimethylboron bromide 41 gave a diastereomeric mixture of 72a–c , which was converted into 3 under the conditions described by Höfle et al 27 To our delight, the material obtained proved to be identical with the authentic compound with respect to the 1 H and 13 C NMR spectra and the optical rotation.…”