Stereoselective Synthesis of the C(53)-C(67) Polyene Fragment of Amphidinol 3

Abstract

A stereoselective synthesis of the polyene fragment C(53)-C(67) of amphidinol 3 is described using a sequence of reduction, benzoylation, and reductive elimination for the stereospecific preparation of the polyene motif as key steps starting from acetylenic precursors.

Isolation, structural determination and synthetic approaches toward amphidinol 3

“…This compound was then converted to the C26-C42 fragment 106 in four steps involving a Claisen rearrangement 100 of a 1,5-diene to introduce the C30-C31 double bond (Scheme 34). 101,105,106,112,115,119,123,125 These three groups are working together on the synthesis of AM3. The rst strategy envisaged to construct AM3 was disclosed by Cossy and Bouzbouz and consisted of the construction of the C30-C31 and the C52-C53 bonds using olenations.…”

“…104 Aer acetylation of the resulting homoallylic alcohol 111, a third cross-metathesis was realized with methyl acrylate to afford compound 112 (C1-C14 fragment) (Scheme 35). 105,106 This C53-C67 fragment corresponds to the skipped polyenic fragment. Two syntheses were realized, one by the Colobert's team 105 and the other one by Cossy et al 106 Colobert et al used their own know-how, a reduction/benzoylation/reductive elimination sequence to synthesize the polyene motif starting from bis-acetylenic precursors.…”

“…105,106 This C53-C67 fragment corresponds to the skipped polyenic fragment. Two syntheses were realized, one by the Colobert's team 105 and the other one by Cossy et al 106 Colobert et al used their own know-how, a reduction/benzoylation/reductive elimination sequence to synthesize the polyene motif starting from bis-acetylenic precursors. The synthesis of the C53-C67 fragment started with butadiyne 113.…”

Boron Carboxylate Catalysis of Homoallylboration

“…All solvents for routine isolation of products and chromatography were reagent grade. Aldehydes were purchased from commercial sources and freshly distilled, except for aldehydes 4g , 9 4h , 10 4i , 11 and 4k , 12 which were synthesized based on literature procedures. Flash chromatography was performed using Silicycle R10030B F60 SiliaFlash silica gel (230–400 mesh) with the indicated solvents.…”

A highly convergent synthesis of the C1–C31 polyol domain of amphidinol 3 featuring a TST-RCM reaction: confirmation of the revised relative stereochemistry

“… 4 Nevertheless, the revision of the configuration at C2 and C51 has severely hampered progress towards the total synthesis of this agent. 5 Hence, the unique molecular architecture and potent biological activity coupled with residual structural and mechanistic ambiguities have prompted several creative approaches 6 to the C1–C31 polyol, 7 C32–C51 bis -tetrahydropyran 8 and the C52–C67 polyene, 9 albeit many of which were accomplished prior to the stereochemical revisions outlined above. Herein, we now describe a novel and expeditious synthesis of the revised C1–C31 fragment of AM3 ( 1 ) using a highly convergent strategy, that confirms the relative configuration of this portion of the natural product.…”