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Biomimetic Synthesis of Urukthapelstatin A by Aza‐Wittig Ring Contraction
Author(s) -
Schwenk Sebastian,
Ronco Cyril,
Oberheide Ansgar,
Arndt HansDieter
Publication year - 2016
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201600994
Subject(s) - chemistry , wittig reaction , stereochemistry , amino acid , combinatorial chemistry , peptide synthesis , ring (chemistry) , peptide , organic chemistry , biochemistry
Marine bacteria produce highly cytotoxic polyheterocyclic cyclopeptide natural products by ribosomal peptide biosynthesis. Among them, urukthapelstatin A features a chain of five 2,4′‐connected azole rings within a cyclo‐octapeptide framework. We report a novel synthesis design that uses only α‐amino acids as starting materials that leads to an efficient and stereoselective total synthesis of urukthapelstatin A. Kinetically favored macro‐thiolactonization and high‐yielding aza‐Wittig heterocyclization to contract the macrocycle were crucial for success. These investigations additionally uncovered the unsuspected configurational lability of the embedded enamide substructure in solution.