Total synthesis and NMR investigations of cylindramide.
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.
Cramer
Nicolai
N
Institut für Organische Chemie der Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany.
Buchweitz
Maria
M
Laschat
Sabine
S
Frey
Wolfgang
W
Baro
Angelika
A
Mathieu
Daniel
D
Richter
Christian
C
Schwalbe
Harald
H
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
D000577:Amides; D011084:Polycyclic Aromatic Hydrocarbons; D013450:Sulfones; C511469:cylindramide; D009952:Ornithine