Total Synthesis of the Anti-Apoptotic Agents Iso- and Bongkrekic Acids

Abstract

The first convergent total synthesis of isobongkrekic acid is reported involving three different stereospecific palladium cross-couplings for the formation of the diene units. Access to bongkrekic acid by this route is also demonstrated. These syntheses involve the formation of several potentially general building blocks.

Homopropargyl alcohol 5,5-diphenylpent-2-yne-1,5-diol

“…Poly-functional homopropargylic alcohols are very useful intermediates in the synthesis of a variety of organic compounds (Kim et al, 2017;Foley & Leighton, 2015;Francais et al, 2010;Hosseyni et al, 2016). Their preparation usually involves multi-step synthesis (Midland et al, 1984).…”

Synthesis and structure of a carbohydrate-fused [15]-macrodilactone

“…Bromination of the terminal alkyne of 11 followed by hydrostannation of the resulting bromoalkyne 12 gave vinylstannane 13 in 55% yield [24]. A second esterification with 4E-5-iodopentenoic acid 14 [25][26][27][28][29] Among the differences, most significant one was that, in 8, the two ester carbonyls were oriented parallel to each other compared to their antiparallel orientation in macrocycle 7. From our prior experience with [13]-macrodilactones, it was inferred that the parallel orientation of two carbonyls didn't represent a ribbon like structure, but rather manifested a cup shape, originating from an attenuation of the screw-sense in diol unit [18].…”

Accelerating Spirocyclic Polyketide Synthesis using Flow Chemistry

“…Spirodienal A (3) was prepared from alkyne 35 in a three step sequence. Firstly, a Sonogashira reaction with vinyl iodide 36, [32] followed by a mixed-metal cis-selective reduction [33] of the C12-C13 internal alkyne and lastly an allylic oxidation to afford the dienal motif. The data for synthetic spirodienal A (3) matched the isolated natural product and signified a first total synthesis, confirming the absolute structure and stereochemistry of the natural product.…”