Synthesis of 9-Substituted Tetrahydrodiazepinopurines:Studies toward the Total Synthesis of Asmarines

摘要

A methodology for the preparation of asmarine analogues has been developed.The asmarines are cytotoxic marine alkaloids with a unique tetrahydro[l,4]diazepino[l,2,3-g,h]purine(THDAP)structure.Three cyclization methods were applied for the preparation of the 9,9-disubstituted 10-hydroxy-THDAP system,namely,aminomercurization,iodocyclization,and acid-catalyzed cyclization.The DMPM group of the NOH functionality and cyanoethyl group of the N-9 atom were found to be the most suitable protecting groups.The structures of all compounds were mainly determined from NMR measurements including ~(15)N chemical shifts obtained from ~(15)NH HMBC spectra.The end products are at least about 1 order of magnitude less active than the natural product asmarine B.