Vecuronium bromide and its advanced intermediates: A crystallographic and spectroscopic study.

[Display omitted] • Neuromuscular blocking agents (NMBAs) induce relaxation of the skeletal muscles. • Vecuronium bromide was synthesized in higher yield, optimizing the literature synthetic process. • A complete analytical characterization of vecuronium bromide and its synthetic intermediates was reported to fill the literature gap. • Using the single-crystal X-ray diffraction (SC-XRD) technique, we unambiguously described the stereochemistry of 10 , a key intermediate for the synthesis of several NMBAs. Vecuronium bromide (Piperidinium, 1-[(2β,3α,5α,16β,17β)-3,17-bis(acetyloxy)-2-(1-piperidinyl)androstan-16-yl]-1-methyl-, bromide; Norcuron®) has been extensively used in anesthesiology practice as neuromuscular blocking agent since its launch on the market in 1982. However, a detailed crystallographic and NMR analysis of its advanced synthetic intermediates is still lacking. Hence, with the aim of filling this literature gap, vecuronium bromide was prepared starting from the commercially available 3β-hydroxy-5α-androstan-17-one (epiandrosterone), implementing some modifications to a traditional synthetic procedure. A careful NMR study allowed the complete assignment of the 1H, 13C, and 15N NMR signals of vecuronium bromide and its synthetic intermediates. The structural and stereochemical characterization of 2β,16β-bispiperidino-5α-androstane-3α,17β-diol, the first advanced synthetic intermediate carrying all the stereocenters in the final configuration, was described by means of single-crystal X-ray diffraction and Hirshfeld surface analysis, allowing a detailed conformational investigation. [ABSTRACT FROM AUTHOR]