Steroids, quaternary derivatives

It is certain that pancuronium is but the first of a series of steroids of this type There is l or example, need for an agent with its favourable properties but with the brevity ot action of suxamethonium. Achievement of this aim may not be too distant since quaternary derivatives of the alkaloid conessine, possessing (in cats at least) the required characteristics have recently been described [75], and dacuronium bromide is now under intensive study by the team responsible for the development of pancuronium. 

Steroidal aminomethyl derivatives have been subjected to some of the reactions typical of Mannich bases, described in Chap. II, usually with the aim of introducing structural modifications of the molecule by means, in particular, of deamination and hydrogen-olysis. The formation of a quaternary ammonium salt (mainly iodomethylatc) by N-alkylation of the base - is also performed to the same end in order to obtain unsaturated deaminated products. ... 

A general problem in the synthesis of steroid compounds is the construction of a dikctone with 5/6 (raws-fused rings and a quaternary carbon atom at the ring junction. Tethering can solve this problem, and we will present two strategies—one using a lactone derived from an iodolactonization reaction, and one using a sulfur atom. 

The main interest in steroidal tertiary amino-derivatives has centred on their quaternisation and Hofmann degradation. As part of an extensive study of amines of many types, McKenna found that equatorial amines react more rapidly than their axial epimers with methyl iodide [32], to give quaternary salts, although the situation was reversed at C( ) [33]. Steric hindrance from the C xs) position made the... 

In order to enhance the sensitivity in steroid analysis, a number of derivatization procedures have been proposed. In most cases, the aim of the derivatization is an increase of the proton affinity of the compound, although the introduction of a fixed charge on a quaternary ammonium or a group with high electron affinity has been described as well. An overview of the derivatives generated is given in Figme 13.4. Most derivatization procedures are applied in combination with ESI-MS. 

Reaction with an oxaziridine. The reagent reacts with the steroidal oxaziridine (1), derived from conamine, to give the quaternary oxaziridinium salt (2). The salt is stable at 20° but decomposes at higher temperatures to (3). 

This first chemoenzymatic synthesis [48] is not included m Fig. 1 but can be considered as a preparation of A-ring synthons in general in the steroid field, and particularly in area of vitamin D (Scheme 9). The stereo control of the quaternary chiral carbon center is one of the important subjects in asymmetrical synthesis. This issue prompted research on the use of chiral monoester 197, which can be obtained in multihundred gram scale by the pig liver esterase (PLE)-mediated hydrolysis of the corresponding symmetrical diester 196 [49]. Thus, an efficient methodology was developed for the preparation of chiral cyclohexene derivatives from cw-diester 196, using PLE in a biphasic system using phosphate buffer and acetone, to afford the chiral half-ester 197. Scheme 9 shows the efficient... 

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