Total Synthesis of Bistramide A and Its 36(Z) Isomers: Differential Effect on Cell Division, Differentiation, and Apoptosis

Abstract

The total synthesis of bistramide A and its 36(Z),39(S) and 36(Z),39(R) isomers shows that these compounds have different effects on cell division and apoptosis. The synthesis relies on a novel enol ether-forming reaction for the spiroketal fragment, a kinetic oxa-Michael cyclization reaction for the tetrahydropyran fragment, and an asymmetric crotonylation reaction for the amino acid fragment. Preliminary biological studies show a distinct pattern of influence of each of the three compounds on cell division, differentiation, and apoptosis in HL-60 cells, thus suggesting that these effects are independent activities of the natural product.

Total Synthesis of (+)-18-epi-Latrunculol A

“…To construct cyclization precursor 5 (Scheme 2B), known aldehyde (−)- 8 (Scheme 2) was readily available from (−)- 10 14 via TBS protection and ozonolysis (Scheme 2). Brown allylation, 15 followed by cross metathesis union employing the Hoveyda-Grubbs 2 nd generation catalyst between the resulting homoallylic alcohol and enone (+)- 7 , proceeded smoothly to provide cyclization precursor (+)- 5 in a 70% yield for the two steps, after separation of the minor epimeric alcohol resulting from the Brown allylation.…”

Synthesis of Fluorinated exo‐Glycals through Modified Julia Olefination

“…The reaction was further extended to the synthesis of tri-and tetrasubstituted enol ethers. [11] Julia olefination has proven to be among the more promising direct methods for the synthesis of fluoroalkenes. [11] Julia olefination has proven to be among the more promising direct methods for the synthesis of fluoroalkenes.…”

A Catalyst Designed for the Enantioselective Construction of Methyl‐ and Alkyl‐Substituted Tertiary Stereocenters

“…To date, seven different routes for the total syntheses of the bistramides have been published 7a. 25 Out of them, five synthetic routes, including the two most recent syntheses,7a, 25b,c,e,f use either chiral auxiliary or chiral reagents to access the C9 methyl‐bearing stereocenter. We used the acetal 17 a as the starting material for a four‐step synthesis of the C4–C13 fragment of the bistramides ( 25 ; Scheme ), with a diastereoselective Mukaiyama aldol26 and a BiBr 3 ‐promoted C‐allylation27 of the tetrahydropyran 24 as the key steps.…”