Synlett 2003(6): 0847-0848
DOI: 10.1055/s-2003-38748
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Convenient Synthesis of Luotonins A and B

Takashi Harayama*, Yoshiaki Morikami, Yasumi Shigeta, Hitoshi Abe, Yasuo Takeuchi
Faculty of Pharmaceutical Sciences, Okayama University, Tsushima-naka 1-1-1, Okayama 700-8530, Japan
Fax: +81(86)2517963; e-Mail: harayama@pharm.okayama-u.ac.jp;
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Publikationsverlauf

Received 5 February 2003
Publikationsdatum:
17. April 2003 (online)

Abstract

Total synthesis of the cytotoxic alkaloid, luotonin A, was achieved using a Pd-assisted biaryl coupling reaction of N-(bromoquinolinyl)methylquinazolinone with Cy3P and KOAc in high yield. Successive treatment of luotonin A with NBS and aq AgNO3 gave luotonin B in good yield.

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General procedure : Pd-assisted coupling reaction of 3 (55 mg, 0.15 mmol) in dry DMF (2 mL) was carried out under the reaction conditions indicated in the Table [1] and under reflux in the argon atmosphere. The reaction mixture was diluted with EtOAc (50 mL) and the precipitates were removed by filtration. The filtrate was washed with aqueous 10% Na2CO3 solution (20 mL) and brine (30 mL). The organic layer was dried over anhydrous MgSO4, then filtered, and the filtrate was evaporated to dryness under reduced pressure. The residue was dissolved in CHCl3 (7 mL) and subjected to column chromatography on silica gel. Elution with hexane/acetone (3:1) gave 1.

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Luotonin A: mp 283-285 °C [lit., [1] 252 °C(dec); lit., [3c] 281-283 °C]. The 1H NMR and IR spectra agreed with those of authentic sample.

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Luotonin B: mp 271-274 °C (lit., [3c] 237-240 °C). The 1H NMR spectrum agreed with that of an authentic sample.