A Convenient Synthesis of Luotonins A and B

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.

Key words

palladium - cytotoxic activity - pyrroloquinazoline alkaloid

References

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12

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.

13

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.

15

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