Total Synthesis of the Proposed Structure for Aromin and Its Structural Revision.
This paper describes the first total synthesis of the proposed structure for aromin, an annonaceous acetogenin possessing an unusual bis-THF ring system, and its 4S,7R-isomer. The key steps involve an oxidative cyclization of a couple of terminal-diene alcohols and an intermolecular metathesis of an alkenyl tetrahydrofuran with an enone carrying a tetrahydrofuranyl lactone. The spectral data of both samples did not match those of aromin. Re-examination of the NMR data using the CAST/CNMR Structure Elucidator and chemical derivations suggested that the real structure of aromin should be revised to be a tetrahydropyran acetogenin, montanacin D. Cytotoxicities in human solid tumor cell lines for synthetic samples were also evaluated.
RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Japan.
Shunya
S
Takahashi
RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Japan.
Daisuke
D
Satoh
RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Japan.
Misato
M
Hayashi
Division of Cell Recognition Study, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University , Sendai 981-8558, Japan.
Kohta
K
Takahashi
Division of Molecular and Cellular Oncology, Miyagi Cancer Center Research Institute , Natori 981-1293, Japan.
Kazunori
K
Yamaguchi
RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Japan.
Takemichi
T
Nakamura
RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Japan.
Hiroyuki
H
Koshino
D054378:Acetogenins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D029061:Annonaceae / Q000737:chemistry; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D045744:Cell Line, Tumor; D003500:Cyclization; D004354:Drug Screening Assays, Antitumor; D005663:Furans / Q000737:chemistry; D006801:Humans; D013058:Mass Spectrometry; D015394:Molecular Structure; D010084:Oxidation-Reduction; D066244:Proton Magnetic Resonance Spectroscopy
D054378:Acetogenins; D005663:Furans; C018674:tetrahydrofuran