Synthetic studies of callyspongiolide: synthesis of the macrolactone core of the molecule

Abstract

A concise synthetic strategy has been developed for the synthesis of the macrolactone core 2 of a unique polyketide callyspongiolide 1. The key features of the strategy included an Evan's asymmetric alkylation, diastereoselective Michael type alkylation, Brown's asymmetric allylation reaction, an allylic alkylation of an activated Z-allylic alcohol and an intramolecular Z-selective intramolecular H-W-E olefination.

Synthesis and Molecular Editing of Callyspongiolide, Part 1: The Alkyne Metathesis/trans‐Reduction Strategy

“…[1] Most notably,h owever,c ell death seems to be triggered by ac aspase-independent pathway:c ompounds that have an on-apoptotic modeo fa ction are particularly interesting leads since apoptotic signaling is suppressed in many tumor cells and one of the causes for drug resistance. [2] Callyspongiolide immediately attracted attention from the synthetic community for this potentially relevant biological profile as well for its scarcity.T hese studies culminated in several partial and total syntheses, [3][4][5][6] which corrected the absolute configurationo riginally assigned to the macrolide core by the isolation team and firmlye stablished the previously unknown configurationo ft he C21 chiral centeri nt he side chain.…”

The Synthesis and Bioactivity of the Marine Macrolide Callyspongiolide

“… Retrosynthetic analysis for S. Ghosh′s synthesis of macrocyclic core 24 of (+)‐callyspongiolide ( 1 ) [30] …”

“… Synthesis of macrocyclic core 24 of (+)‐callyspongiolide ( 1 ) by S. Ghosh and co‐workers [30] . Reagents and conditions: i) O 3 , Me 2 S, −78 °C–rt, 3 h; ii) (−)‐Ipc 2 BOMe, allylMgBr, Et 2 O, −78 °C, 70 % (2 steps), >19:1 dr; iii) acryloyl chloride, Et 3 N, CH 2 Cl 2 , 0 °C, 92 %; iv) Grubbs first‐generation catalyst, CH 2 Cl 2 , reflux, 90 %; v) MeLi, CuI, Et 2 O, 0 °C, 96 %; vi) LiBH 4 , THF, 0 °C, 98 %; vii) TBSOTf, 2,6‐lutidine, CH 2 Cl 2 , 0 °C–rt, 95 %; viii) KOH, 18‐crown‐6, THF/H 2 O, rt, 72 %; ix) DMP, NaHCO 3 , CH 2 Cl 2 , 0 °C–rt, quant.…”

A Ring Closing Metathesis Approach to the Formal Synthesis of (+)‐Callyspongiolide

“…were reported in 2018. Partial syntheses of this natural product have also been reported, with the synthesis of the macrocyclic core of (+)‐callyspongiolide ( 1 a ) by S. Ghosh [28] and the synthesis of the unsaturated side‐chain of (−)‐callyspongiolide ( 2 ) by Kotora [29] both reported in 2016, and a further synthesis of C3–C15 fragment of the macrocyclic core of (+)‐callyspongiolide ( 1 a ) published by Mohapatra in 2018 [30] . Meanwhile our research group has been working on the synthesis of (+)‐callyspongiolide ( 1 ) (based on the original structural assignment) via a RCM approach since prior to any of these publications.…”