Publication Date:
2017-08-09
Description:
Oxoisoaporphine alkaloids are conveniently prepared via direct ring metalation of alkoxy-substituted isoquinolines at C-1, followed by reaction with iodine. Subsequent Suzuki cross-coupling of the resulting 1-iodoisoquinolines to methyl 2-(isoquinolin-1-yl)benzoates and intramolecular acylation of the corresponding carboxylic acids with Eaton’s reagent afforded five alkaloids of the oxoisoaporphine type. The yield of the cyclization step strongly depends on the electrophilic properties of ring B. An alternative cyclization protocol via directed remote metalation of ester and amide intermediates was investigated thoroughly, but found to be not feasible. Two of the alkaloids showed strong cytotoxicity against the HL-60 tumor cell line. Beilstein J. Org. Chem. 2017, 13, 1564–1571. doi:10.3762/bjoc.13.156
Keywords:
directed ortho/remote metalationEaton’s reagentisoquinolinesSuzuki cross-coupling
Electronic ISSN:
1860-5397
Topics:
Chemistry and Pharmacology
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