First Total Synthesis of Neoantimycin

Abstract

The first total synthesis of neoantimycin (1), an unusual ring-extended antibiotic of the antimycin class, has been achieved, using intramolecular transesterification for construction of the 15-membered tetralactone core.

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

“…11 The synthesis used an intramolecular trans-esterication to provide the 15-membered tetralactone core, and it began with the synthesis of a methylbutyrate, 144, which was prepared from L-valine in three steps. 11 The synthesis used an intramolecular trans-esterication to provide the 15-membered tetralactone core, and it began with the synthesis of a methylbutyrate, 144, which was prepared from L-valine in three steps.…”

“…As shown by their structures, natural variations occur at C7 and C8. Further analysis of the antimycin A mixture later revealed the presence of two additional minor components, antimycins A 5 (9,10) and A 6 (11,12), 24,25 and subsequent NMR spectroscopic analysis and high-performance liquid chromatographic (HPLC) separation indicated that each of antimycins A 1 -A 4 is a mixture of two isomers. 26,27 Joyce Liu received her B.S.…”

“…Since their initial isolation in 1949, 1 antimycin-type depsipeptides have received considerable interest because of their potent and diverse biological activities. [9][10][11] It will also discuss the recent identication and characterization of hybrid nonribosomal peptide synthetase (NRPS)-polyketide synthase (PKS) assembly lines responsible for the biosynthesis of antimycin-type depsipeptides, 8,12 which has prompted the generation of a signicant number of new antimycin analogues. 2 More recently, several classes of antimycin-type depsipeptides have also been shown to have promising anti-cancer and anti-inammatory activities.…”

“…1). Further analysis of the antimycin A mixture later revealed the presence of two additional minor components, antimycins A 5 (9, 10) and A 6 (11,12), 24,25 and subsequent NMR spectroscopic analysis and high-performance liquid chromatographic (HPLC) separation indicated that each of antimycins A 1 -A 4 is a mixture of two isomers. 23 This family of compounds is characterized by a nine-membered dilactone ring substituted with one alkyl (C7), one acyloxy (C8), two methyl moieties (C4 and C9), and an amide linkage (C3) connecting to a 3-formamidosalicylic acid.…”

“…It will include the discovery, isolation, and structural variation of the four classes of antimycintype depsipeptide natural products that differ by ring size 1,[5][6][7][8] and discuss the development of total synthesis approaches for this family of compounds. [9][10][11] It will also discuss the recent identication and characterization of hybrid nonribosomal peptide synthetase (NRPS)-polyketide synthase (PKS) assembly lines responsible for the biosynthesis of antimycin-type depsipeptides, 8,12 which has prompted the generation of a signicant number of new antimycin analogues. 13 The biological activities reported for this family of compounds, with particular focus on their anti-cancer properties, will also be covered here.…”