Biomimetic Synthesis of Urukthapelstatin A by Aza‐Wittig Ring Contraction. Issue 28 (6th October 2016)

• Record Type: Journal Article
• Authors: Schwenk, Sebastian; Ronco, Cyril; Oberheide, Ansgar; Arndt, Hans‐Dieter
• Is Part Of: European journal of organic chemistry. Issue 28(2016)
• Page Start: 4795
• Page End: 4799
• Publication Date: 2016-10-06
• Subjects: Amino acids -- Cyclization -- Cyclopeptides -- Macrocycles -- Stereoselectivity -- Total synthesis; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201600994
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract : 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. Abstract : 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.