Structural revision of halipeptins: synthesis of the thiazoline unit and isolation of halipeptin C

Chemistry and Biology of Anti-Inflammatory Marine Natural Products:Molecules Interfering with Cyclooxygenase, NF-kB and Other Unidentified Targets

“…This revision was based on comparison of the spectral data of the natural metabolites with those of a synthetic thiazoline model. Further support came from the comparison of GIAO (gauge including atomic orbitals) calculated 13 C and 15 N NMR chemical shifts of oxazetidine and thiazoline model compounds with those of halipeptin A [66,67]. Finally, in the framework of a synthetic program directed to the synthesis of halipeptins (see infra), Faulkner reported the isolation of a further member of this family, halipeptin D (90) (Fig.…”

“…In 2002, along with the isolation, from the same specimen of Haliclona sp., of a new minor related cyclodepsipeptide, named halipeptin C (89) (Fig. 15), GomezPaloma et al reported a structural revision of halipeptins, reassessing the heterocyclic oxazetidine ring as a thiazioline moiety [66]. This revision was based on comparison of the spectral data of the natural metabolites with those of a synthetic thiazoline model.…”

“…Their approach was based on the consideration that the natural product contains crowded fragments, and therefore the first issue was to join together the sterically hindered units with other amino acid residues. Moreover, since only the relative configuration [65,66] at C-3 and C-4 of the decanoic acid residue (3S,4R,7S or 3R,4S,7S) was known, the work of Ma and co-workers was also instrumental for establishing the final absolute configuration 3S,4R,7S for the decanoic acid.…”

Die Jagd auf Moleküle, die nie existiert haben: Falsch zugeordnete Naturstoffstrukturen und die Rolle der chemischen Synthese in der modernen Strukturaufklärung

“…In anderen Fällen diente die chemische Synthese dazu, das Vorliegen eines bestimmten Strukturelements zu bestätigen. Bei der Neuzuordnung der Struktur von Halipeptin A hat das Team von Gomez‐Paloma nicht nur ein weiteres Massenspektrometrie‐Experiment durchgeführt, sondern auch eine Modellverbindung synthetisiert, die das neu vorgeschlagene Thiazolin‐Element enthielt, um dessen spektroskopische Eigenschaften mit denen des Naturstoffs zu vergleichen 28. Auch die Gruppe um Hirama stellte einen großen Teil des Kedarcidin‐Chromophors her (Tabelle 4), um sich von der veränderten Konnektivität und Konfiguration zu überzeugen, die sie in ihrer revidierten Struktur vorzuschlagen beabsichtigten 74.…”

Total Synthesis of Halipeptins A and D and Analogues

“…and showed that halipeptin A exhibits impressive antiinflammatory properties that exceed those of well‐established drugs 1. Their later isolation of halipeptin C prompted them to revise their structural assignment to that of thiazoline containing macrocycles as shown for halipeptins A–C ( 1 a – c ) in Scheme leaving open the absolute configuration at the marked positions 2. The isolation of a fourth member of this family of marine natural products, halipeptin D ( 1 d , Scheme ), by the group of Faulkner soon after,3 did not reveal further stereochemical details but raised our interest in this class of natural products once halipeptin D ( 1 d ) was reported to exhibit strong inhibitory activity in vitro against different human cancer‐cell lines 4…”