Total Synthesis of the Proposed Structure for Aromin and Its Structural Revision

• Published in: Journal of organic chemistry Vol. 81; no. 22; pp. 11222 - 11234
• Main Authors: Takahashi, Shunya, Satoh, Daisuke, Hayashi, Misato, Takahashi, Kohta, Yamaguchi, Kazunori, Nakamura, Takemichi, Koshino, Hiroyuki
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 18-11-2016
• Subjects: Acetogenins - chemical synthesis; Acetogenins - chemistry; Acetogenins - pharmacology; Annonaceae - chemistry; Carbon-13 Magnetic Resonance Spectroscopy; Cell Line, Tumor; Cyclization; Drug Screening Assays, Antitumor; Furans - chemistry; Humans; Mass Spectrometry; Molecular Structure; Oxidation-Reduction; Proton Magnetic Resonance Spectroscopy
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.6b02187

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.