Synthesis of 9-substituted tetrahydrodiazepinopurines: studies toward the total synthesis of asmarines.
A methodology for the preparation of asmarine analogues has been developed. The asmarines are cytotoxic marine alkaloids with a unique tetrahydro[1,4]diazepino[1,2,3-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.
Pappo
Doron
D
School of Chemistry, Tel-Aviv University, Ramat Aviv 69978, Israel.
Shimony
Shiri
S
Kashman
Yoel
Y
D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D003500:Cyclization; D004224:Diterpenes / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011687:Purines / Q000138:chemical synthesis*; D013237:Stereoisomerism
D004224:Diterpenes; D007202:Indicators and Reagents; D011687:Purines