An improved synthesis of V-PROLI/NO, a cytochrome P450-activated nitric oxide prodrug

An improved synthesis of V-PROLI/NO, a cytochrome P450-activated nitric oxide (NO) prodrug, in an overall yield of 26% in four steps from prolinol is reported; the previously published yield of this transformation was 1%. Using this revised strategy, the sarcosine analogue (14) of V-PROLI/NO was prepared. Finally, the methyl ester of V-PROLI/NO (15) was found to be an esterase-activated prodrug form of V-PROLI/NO.

Graphical abstractAn improved synthesis of V-PROLI/NO, a cytochrome P450-activated nitric oxide prodrug, and synthesis of its sarcosine analogue are reported.Download full-size image