Total Synthesis of Aigialomycin D Using a Ramberg−Bäcklund/RCM Strategy

Abstract

The bioactive resorcylic acid lactone aigialomycin D (1) has been synthesized by a novel combination of ring-closing metathesis (RCM) and Ramberg-Bäcklund reactions. This synthetic strategy enables the C1'-C2' alkene to be masked as a sulfone during formation of the macrocycle by ring closing metathesis at the C7'-C8' olefin, thus avoiding competing formation of a cyclohexene. A subsequent Ramberg-Bäcklund reaction efficiently produces the C1'-C2' E-alkene. This combined RCM/Ramberg-Bäcklund reaction strategy should be widely applicable to the synthesis of macrocyclic dienes.

Asymmetric Formal Synthesis of (–)‐Swainsonine by a Highly Regioselective and Diastereoselective Allylic Amination Using Chlorosulfonyl Isocyanate

“…In view of these unsuccessful results, we changed our synthetic plan to a two‐step transformation, which involved a partial reduction of the olefin in α,β‐unsaturated ester 7 and subsequent reduction of the ester group. After an extensive screening of the optimal reaction conditions, we found that a combination of sodium borohydride and cuprous chloride in the presence of cyclohexene furnished our desired α,β‐saturated ester 8 in 95 % yield 22. The reduction of ester 8 under standard conditions [LiAlH 4 , tetrahydrofuran (THF)] afforded primary alcohol 9 , which was subjected to an Appel reaction (PPh 3 , CBr 4 , and Et 3 N) to furnish compound 10 in 87 % yield.…”

A ring closing metathesis strategy for carbapyranosides of xylose and arabinose

“…26 The carba-xyloside precursor 19 , which was previously prepared from L-tartaric, was prepared here via a more concise route, using a strategy similar to that used for 14 . 27 Thus, zinc mediated reductive opening on the 5-deoxy-5-iodo- d -arabinofuranoside 16 afforded enal 17 .…”

Recent progress regarding the bioactivities, biosynthesis and synthesis of naturally occurring resorcinolic macrolides

“…Further syntheses of aigialomycin D (16) were completed by the groups of Pan and Harvey [95,96] . The key features of the Pan approach included the application of two Julia-Kocienski couplings to establish the E geometry of both olefins and a Yamagushi macrocyclization.…”