title: Divergent solid-phase synthesis of natural product-inspired bipartite cyclodepsipeptides: total synthesis of seragamide A.
abstract: 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.
authors.affiliation: Max-Planck-Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund (Germany), Fax: (+49) 3641948212; Friedrich-Schiller-Universität, Institute of Organic and Macromolecular Chemistry, Humboldtstrasse 10, 07743 Jena (Germany). hd.arndt@uni-jena.de.
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Arndt
authors.forename: Stefano
authors.initials: S
authors.lastname: Rizzo
authors.forename: Christina
authors.initials: C
authors.lastname: Nöcker
authors.forename: Vijay N
authors.initials: VN
authors.lastname: Wakchaure
authors.forename: Lech-Gustav
authors.initials: LG
authors.lastname: Milroy
authors.forename: Vanessa
authors.initials: V
authors.lastname: Bieker
authors.forename: Abram
authors.initials: A
authors.lastname: Calderon
authors.forename: Tuyen T N
authors.initials: TT
authors.lastname: Tran
authors.forename: Silke
authors.initials: S
authors.lastname: Brand
authors.forename: Leif
authors.initials: L
authors.lastname: Dehmelt
authors.forename: Herbert
authors.initials: H
authors.lastname: Waldmann
mesh_terms: D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D047630:Depsipeptides / Q000138:chemical synthesis* / Q000737:chemistry; D060327:Solid-Phase Synthesis Techniques
chemical_list: D001688:Biological Products; D047630:Depsipeptides; C057531:jasplakinolide
keywords: cyclodepsipeptides; macrocycle; natural products; relay-ring-closing metathesis; solid-phase synthesis