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Divergent Solid‐Phase Synthesis of Natural Product‐Inspired Bipartite Cyclodepsipeptides: Total Synthesis of Seragamide A
Author(s) -
Arndt HansDieter,
Rizzo Stefano,
Nöcker Christina,
Wakchaure Vijay N.,
Milroy LechGustav,
Bieker Vanessa,
Calderon Abram,
Tran Tuyen T. N.,
Brand Silke,
Dehmelt Leif,
Waldmann Herbert
Publication year - 2015
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201500368
Subject(s) - depsipeptide , polyketide , metathesis , total synthesis , combinatorial chemistry , bipartite graph , chemistry , stereochemistry , natural product , ring closing metathesis , enantioselective synthesis , biosynthesis , organic chemistry , mathematics , combinatorics , polymer , graph , catalysis , polymerization , enzyme
Macrocyclic natural products (NPs) and analogues thereof often show high affinity, selectivity, and metabolic stability, and methods for the synthesis of NP‐like macrocycle collections are of major current interest. We report an efficient solid‐phase/cyclorelease method for the synthesis of a collection of macrocyclic depsipeptides with bipartite peptide/polyketide structure inspired by the very potent F‐actin stabilizing depsipeptides of the jasplakinolide/geodiamolide class. The method includes the assembly of an acyclic precursor chain on a polymeric carrier, terminated by olefins that constitute complementary fragments of the polyketide section and cyclization by means of a relay‐ring‐closing metathesis (RRCM). The method was validated in the first total synthesis of the actin‐stabilizing cyclodepsipeptide seragamide A and the synthesis of a collection of structurally diverse bipartite depsipeptides.