Biomimetic Synthesis of Urukthapelstatin A by Aza-Wittig Ring Contraction

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‐amin...

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Bibliographic Details
Published in:European journal of organic chemistry 2016-10, Vol.2016 (28), p.4795-4799
Main Authors: Schwenk, Sebastian, Ronco, Cyril, Oberheide, Ansgar, Arndt, Hans-Dieter
Format: Article
Language:English
Subjects:
Amino acids
Chemical Sciences
Cyclization
Cyclopeptides
Macrocycles
Stereoselectivity
Total synthesis
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Summary: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. Constraining well dosed: The first stereoselective total synthesis of urukthapelstatin A that employs a novel synthesis design is reported. Kinetically favored macro‐thiolactonization and high‐yielding aza‐Wittig heterocyclization to contract the macrocycle are crucial for success. The embedded enamide substructure of the target molecules slowly isomerizes in solution.
ISSN:1434-193X
1099-0690
DOI:10.1002/ejoc.201600994