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
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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.
