An efficient, PIFA mediated approach to benzo-, naphtho-, and heterocycle-fused pyrrolo[2,1-c][1,4]diazepines. An advantageous access to the antitumor antibiotic DC-81.
[reaction: see text] The synthesis of a series of optically pure benzo-, naphtho-, and heterocycle-fused pyrrolo[2,1-c][1,4]-diazepin-5,11-dione derivatives starting from l-proline methyl ester is presented. The synthetic plan includes an aroylation step at the proline nitrogen followed by transformation of the ester residue into a N-methoxyamide group. The subsequent key cyclization step embraces the PIFA mediated formation of a N-acylnitrenium intermediate and its succeeding intramolecular trapping by the aromatic ring. The presented general approach solves the need of starting from not very accessible amino (or a related functionality) aromatic starting materials, and its effectiveness is demonstrated in the synthesis of the antitumor antibiotic DC-81.
Correa
Arkaitz
A
Departamento de Química Orgánica II, Facultad de Ciencia y Tecnología, Universidad del País Vasco-Euskal Herriko Unibertsitatea (UPV/EHU), P.O. Box 644-48080, Bilbao, Spain.
Tellitu
Imanol
I
Domínguez
Esther
E
Moreno
Isabel
I
Sanmartin
Raul
R
D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D001569:Benzodiazepines / Q000138:chemical synthesis*; D003500:Cyclization; D015195:Drug Design; D007097:Imines / Q000138:chemical synthesis*; D008968:Molecular Conformation; D009943:Organophosphorus Compounds / Q000138:chemical synthesis*; D011720:Pyrazoles / Q000737:chemistry*; D011758:Pyrroles / Q000138:chemical synthesis*; D013457:Sulfur Compounds / Q000138:chemical synthesis*
C474072:(11aS)-8-hydroxy-7-methoxy-1,2,3,11a-tetrahydro-5H-pyrrolo(2,1-c)(1,4)benzodiazepin-5-one; D000970:Antineoplastic Agents; D007097:Imines; D009943:Organophosphorus Compounds; D011720:Pyrazoles; D011758:Pyrroles; D013457:Sulfur Compounds; C500922:p-bromophenyl methyl sulfoximine; C438462:pyrrolo(2,1-c)(1,4)benzodiazepine; D001569:Benzodiazepines