Total synthesis of the (+)-antimycin A3 family: structure elucidation of (+)-antimycin A3a

Antimycin-type depsipeptides: discovery, biosynthesis, chemical synthesis, and bioactivities

“…13,60 Evidence for this pathway has been provided by gene disruption experiments, heterologous expression of the gene cluster, and biochemical analysis. 59 Similarly, AntB has been shown to generate diversity at the C8 acyloxy group, and Streptomyces DantB mutants have been used to produce several deacylated antimycins (40,42,43,45,69,70). 52,57 Moreover, the activities of AntB, C, D, and E were individually characterized in vitro, and the enzymatic synthesis of the dilactone scaffold of antimycin was achieved with puried AntC, D, E, F, G, and M and their corresponding substrates and cofactors.…”

Natural occurrence, biological activities and synthesis of eight-, nine-, and eleven-membered ring lactones

“…In 2003, 70 the same Japanese group reported the stereoselective synthesis of (+)-antimicym A 3a (95) and established the absolute configuration at the C2´ position on the acyloxy side chain. The authors used (S)-(-)-methylbenzylamine for the preparation of the seco acids 108c/108d, following the same sequence of reactions early used for the synthesis of unnatural ent-96.…”

Total Synthesis of the (+)‐Antimycin A Family

“…For example, antimycin A 3 (AA 3 ) was found to be a mixture of two compounds with a (S)-2-methylbutanoate or 3-methylbutanoate at the C-8 position, termed AA 3a and AA 3b (Figure 2), respectively. [9] Thus, until now, AA complexes (mixtures of AAs) have been used for biological and biochemical studies in many cases. From a structural point of view, a 3-formamidosalicylic moiety is required to inhibit electron transport.…”

“…Several groups have previously accomplished the enantioselective total synthesis of AA 3b (previous name AA 3 ), [11a-11d] AA 3a , [9] and AA 9 [12] bearing a butyl sidechain at the C-7 position (called 7-butyl-AAs, see Figure 2). Early attempts at the asymmetric total synthesis of AA 3a and AA 3b were constrained by 1) the poor efficiency of the construction of the stereochemistry at the C-7/C-8 position, 2) the low efficiency of the cyclization to form the ninemembered dilactone ring, and 3) lengthy synthetic routes with low overall yields.…”

“…www.eurjoc.orgoped towards the total [9,11] and formal [13] syntheses of AA 3b . Among them, the aldol reaction is the most promising methodology, and Wu and Wang recently reported that excellent stereoselectivity with high chemical yield was achieved by using Crimmins' aldol conditions in their expeditious total synthesis of AA 3b .…”