Steroids, deamination

When complete product analyses were performed after deamination of the 5a-cholestan 3-yl amines [4, ], the results (Table 28) provided support for the Cohen and Jankowski mechanism, although there is some disagreement between authors as to exact yields of products. The notable features are again higher yields of olefin from the axial amine, predominant retention in substitution products, and only slight sensitivity to solvent composition except for a marked increase in the yield of inverted alcohol in aqueous acetic acid. We may therefore consider the solvated diazonium acetate ion-pair as the key species in the steroid deamination reactions, although further work is needed to estabHsh a complete parallel with the data for decalyl amines. 

Most hormones have a half-life in the blood of only a few minutes because they are cleared or metabolized very rapidly. The rapid degradation of hormones allows target cells to respond transiently. Polypeptide hormones are removed from the circulation by serum and cell surface proteases, by endocytosis followed by lysosomal degradation, and by glomerular filtration in the kidney. Steroid hormones are taken up by the liver and metabolized to inactive forms, which are excreted into the bile duct or back into the blood for removal by the kidneys. Catecholamines are metaboli-cally inactivated by O-methylation, by deamination, and by conjugation with sulfate or glucuronic acid. 

The same polymer-supported organotin reagent was also used in the Barton-type deoxygenation of steroid derivatives, sugar derivatives and diols160. Furthermore, the radical deamination of secondary and tertiary amines via the corresponding isocyanides was also reported160,169. 

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. ... 

Deamination is the most commonly performed reaction of steroid Mannich bases. It is usually carried out by heating the base in the presence of acetic acid/acctic anhydride, - by column chromatography on silica gel, by heat decomposition of the corresponding hydrochloride or iodomethylate, or under suitably modified reaction conditions leading directly to the unsaturated final pnxluct starting from the usual Mannich reactants (Chap. II, A.2). 

Fig. 175. Deamination reaction of vinylogous Mannich bases of steroid derivatives.

Our understanding of the deamination of primary aliphatic amines by the action of nitrous acid has gained much from studies of alicyclic compounds, including Shoppee s extensive work in the steroid field. 

The current view of deaminations of cyclohexylamine and steroid derivatives is based upon investigations by Cohen and... 

Another very simple approach to 18,20-oxygenated steroids is nitrous acid deamination of pyrrolines of the type CCXXXVI. In this manner, Buzetti et al. 165) prepared 18-hydroxyprogesterone CCXXXII. The pyrrolines (CCXXXVI) are readily accessible from the demethyl-conanine type (CCXXXIV) by the Ruschig method. The position of the double bond was established 98) in a model pyrroline from the absence... 

The White deamination procedure has been used in the tran.sformation of the steroidal alkaloids tomatidine (1) and solasodine into dihydroneotigogenin (4) and dihydrotigogenin, respectively. Thus (1) was converted into the N,22-dihydride... 

A review on the acid promoted decomposition of a-diazoketones contains some steroidal examples.88 The full account was reported of the conversion of a-azido-ketones into cyano-carboxylic acids promoted by bromine in acetic acid.89 A general review on new reagents in natural product chemistry included the deamination of amines via the isonitriles, isothiocyanates, and isoselenocyanates reported... 

Glutamate dehydrogenase is an allosteric protein modulated positively by ADP, GDP, and some amino acids and negatively by ATP, GTP, and NADH. Its activity is affected by thyroxine and some steroid hormones in vitro. Glutamate dehydrogenase is the only amino acid dehydrogenase present in most cells. It participates with appropriate transaminases (aminotransferases) in the deamination of other amino acids. 

Steroidal amines with nitrogen at C-3 or C-20 can be converted into steroidal hormones." Beckmann rearrangement of the oxime (45) of funtumine gives 3a,17j3-diamino-5a-androstane (46). Ruschig deamination of the latter gives androstanedione In the same way, the alkaloids of H. floribunda,... 

Nitrous acid deamination of 3a,20)3-diacetoxy-12a-amino-5/5-pregnan-ll-one afforded some c-nor-o-homo-steroid, but the main products were 12 -methyl-l 1-ketones produced by 13-methyl migration which, on treatment with base, underwent retroaldol reaction to give 3a-hydroxy-12-methyl-18-nor-5) -androst-12-en-1 l-one. ° Similar deamination of the 9a-amino-ll-ketone (500) also resulted in methyl migration to a mixture of the 1(10)- and 5(10)-olefins (502) and 10a-hydroxy-compound (501). Epoxidation of the two olefins and subsequent treatment with acid gave 20j5-hydroxy-9 -methyl-19-norpregna-l,3,5(10)-trien-ll-one. 

Among the diverse reactions carried out by mammalian CYPs are iV-dealkylation, O-deaUcylation, aromatic hydroxylation, A-oxidation, -oxidation, deamination, and dehalogenation (Table 3-2). CYPs are involved in the metabolism of dietary and xenobiotic agents, as well as the synthesis of endogenous compounds that are derived from cholesterol e.g., steroid hormones and bile adds). 

Steroidal and other primary amines were converted into perhydro-dioxazepines, for example (58), by treatment with paraformaldehyde and a i)/c-diol. °° Deamination of N,N-dimethylamines with CCI3CH2OCOCI was exemplified by the conversion of the 3a-dimethylaminopregnane (59) into the A -compound. The deamination appears to be controlled by stereoelectronic factors as conessine underwent demethylation to give (60). Cleavages of 16a,17a-epimino-20-oxo-steroids and their 20-hydrazones with thioacetic acid were reported, as were the reactions of 16a,17a-episulphides with HSCN... 

Angular methyl migrations of this type have been observed in the heterolyses of 5a-substituted steroids, a process known as the Westphalen rearrangement 234), As an example, the nitrous acid deamination of diacetoxy amine 148 is shown below 235), The presence of an electronegative substituent in the 6P-position is apparently usually a prerequisite for the Westphalen rearrangement. 

Deamination of 9a-amino-ll-keto steroids (e.g., 337) (400) is an alternate means to accomplish the Cio- Cg methyl rearrangement (400, 432). In the fluorination of a steroid with methyl hypofluorite,... 

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