title: Total synthesis and NMR investigations of cylindramide.
abstract: Cylindramide (1) was built up from three components: a hydroxyornithine derivative 7, a tetrazolylsulfone 8, and a substituted pentalene subunit 9. Derivative 7 was prepared in a six-step reaction sequence involving the Wittig reaction and a Sharpless asymmetric dihydroxylation starting from N-Boc-3-aminopropanal (12). Tetrazolylsulfone 8 was accessible in four steps from dioxinone 22. The synthesis of the pentalene fragment 9 started from cycloocta-1,5-diene 26, that was converted into enantiopure bicyclo[3.3.0]octanedione 29. The latter was functionalized to give derivative 9. The total synthesis was accomplished by inducing C-C bond formation by Sonogashira coupling of derivatives 9 and 7 followed by olefination with tetrazolylsulfone 8 under Julia-Kocienski conditions, macrocyclization, and subsequent Lacey-Dieckmann condensation to form the tetramic acid unit. As indicated by extensive 1H and 13C NMR spectroscopic investigations (DQF-COSY, ROESY spectra), the stereochemistry of synthetic cylindramide (1) corresponds with that of the naturally occurring product. ROE data were used for molecular modeling of the lowest-energy structures for cylindramide.
authors.affiliation: Institut für Organische Chemie der Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany.
authors.forename: Nicolai
authors.initials: N
authors.lastname: Cramer
authors.forename: Maria
authors.initials: M
authors.lastname: Buchweitz
authors.forename: Sabine
authors.initials: S
authors.lastname: Laschat
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Frey
authors.forename: Angelika
authors.initials: A
authors.lastname: Baro
authors.forename: Daniel
authors.initials: D
authors.lastname: Mathieu
authors.forename: Christian
authors.initials: C
authors.lastname: Richter
authors.forename: Harald
authors.initials: H
authors.lastname: Schwalbe
mesh_terms: D000577:Amides / Q000138:chemical synthesis*; D006900:Hydroxylation; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009952:Ornithine / Q000737:chemistry; D011084:Polycyclic Aromatic Hydrocarbons / Q000138:chemical synthesis*; D013237:Stereoisomerism; D013450:Sulfones / Q000737:chemistry
chemical_list: D000577:Amides; D011084:Polycyclic Aromatic Hydrocarbons; D013450:Sulfones; C511469:cylindramide; D009952:Ornithine