Total Synthesis of SR 121463 A, a Highly Potent and Selective Vasopressin V2 Receptor Antagonist

摘要: SR 121463 A, 1, is a promising nonpeptide prototype for potent and selective antagonism of the vasopressin V2 receptor subtype and, thus, candidate control clinically debilitating condition hyponatremia its associated syndromes. In present work, we novel stereoselective synthesis that stems from preparation three key intermediates:  substituted benzenesulfonyl chloride 2, N-protected oxindole 3, protected dibromide 4. The 1 has been achieved in good overall yield, each step proceeding greater than 80% yield. addition, intermediate 2 syn isomer were prepared with complete stereochemistry. latter reduction appears to proceed by lithium cation mediated chelation control. Molecular mechanics calculations MM3* MMFF force fields underscore geometric energetic aspects reaction.