190330-54-2Relevant academic research and scientific papers
Total synthesis of SR 121463 A, a highly potent and selective vasopressin V2 receptor antagonist
Venkatesan,Davis,Altas,Snyder,Liotta
, p. 3653 - 3661 (2007/10/03)
SR 121463 A, 1, is a promising nonpeptide prototype for potent and selective antagonism of the vasopressin V2 receptor subtype and, thus, a candidate for control of the clinically debilitating condition of hyponatremia and its associated syndromes. In the present work, we present a novel and stereoselective synthesis that stems from the preparation of three key intermediates: the substituted benzenesulfonyl chloride 2, the N-protected oxindole 3, and protected dibromide 4. The synthesis of 1 has been achieved in good overall yield, each step proceeding in greater than 80% yield. In addition, intermediate 2 and the syn isomer of 1 were prepared with complete control of stereochemistry. The latter reduction appears to proceed by lithium cation mediated chelation control. Molecular mechanics calculations with the MM3* and MMFF force fields underscore geometric and energetic aspects of the reaction.
