Asymmetric Total Synthesis of Amphirionin-2

Abstract

A convergent route for the asymmetric total synthesis of potent anticancer polyketide natural product amphirionin-2 has been developed. Our initial synthetic trials revealed that the proposed structures of amphirionin-2 need to be revised consistent with a recent report of Fuwa et al., where the actual structure of amphirionin-2 was established. The key features of our synthesis comprised Sharpless asymmetric dihydroxylation, followed by cycloetherification, Wittig olefination, Julia−Kocienski olefination, and Crimmins propionate aldol reaction.

Marine natural products

“…345 Two groups have independently synthesised and determined the full stereostructure of amphirionin-2 886. 346,347 The role of synthesis in solving congurational relationships within marine polycyclic ethers has been reviewed. 348 A review of the toxic metabolites produced by Karenia brevisulcata has been published, 349 as have reviews of models of food chain webs of ciguatera in Australia, 350 and the effects of okadaic acids and dinophysistoxins on sh.…”

Synthesis of the Key Skeleton of Phosphoeleganin

“…5a 6 Sulfone 6 was then benzylated by using BnBr/NaH/TBAI and then subjected to oxidative cleavage in the presence of NaIO 4 /OsO 4 to give the corresponding aldehyde, which was subsequently reduced with NaBH 4 to obtain alcohol 9 . This was then treated with 1-phenyl-1 H -tetrazole-5-thiol ( 10 ) by following a Mitsunobu protocol 5a b h , 7 to give the corresponding sulfide which further was oxidized with (NH 4 ) 6 Mo 7 O 24 ·4H 2 O/H 2 O 2 5b h , 8 to provide sulfone 11 in a good overall yield.…”

Total Synthesis of Strasseriolide A

“…Architecturally strasseriolides A–D are 18-membered macrolides bearing five methyl centers, two trisubstituted trans -alkenes, and a free carboxylic acid, where the hydroxy or keto functionalities vary among the members. Attractive structural features, promising bioactivity, and the natural scarcity of these macrolides together with our long association with natural product chemistry prompted us to envisage their chemical synthesis. We initially planned to develop a route for the synthesis of strasseriolide A presuming its conversion to strasseriolide B by selective reduction of the keto functionality.…”

“…The 1 H and 13 C­{ 1 H} NMR data (see Table S1 in Supporting Information) and optical rotation of the synthesized compound 1 were recorded and compared with the reported data. The 1 H NMR data and optical rotation observed [α] D 25 = +9.63 ( c 0.49, MeOH); reported [α] D 25 = +8.0 ( c 0.45, MeOH)} were in good agreement with the literature values . However, some anomalies in 13 C­{ 1 H} NMR data were observed when the data were collected in a concentration of 15.5 mM in CD 3 OD.…”