- Vecuronium bromide and its advanced intermediates: A crystallographic and spectroscopic study
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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.
- Ciceri, Samuele,Colombo, Diego,Ferraboschi, Patrizia,Grisenti, Paride,Iannone, Marco,Mori, Matteo,Meneghetti, Fiorella
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- Synthesis of 2β,16β-bis-(4'-dimethyl-1'-piperazino)-3α,17β-diacetoxy-5α-androstane dibromide and related compounds
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A series of bisquaternary ammonio steroids having androstane skeletons have been prepared some of which possessed high neuromuscular blocking activity. One of the series 2β,16β-bis-(4'-dimethyl-1'-piperazino)-3α,17β-diacetoxy-5α-androstane-dibromide (9, pipecurium bromide, Arduan) has proved to be a clinically useful agent of medium duration of action without side effects. The preparation of these ammonio steroids and structure-activity relationships within the series are described. The structure of 9 and related compounds was elucidated by spectrometric methods Ir, NMR and MS.
- Tuba
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p. 342 - 346
(2007/10/02)
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