Steroids normal- -series

Addition of dimethylsulfoxonium methylide has also been studied in the retro steroid (9, 10a) series. Results are somewhat different from observations in the normal series. Thus only the 6, 7)3-methylene adduct is obtained from a 4,6-dien-3-one while 6-chloro-9) ,10a-l,4,6-trien-3-ones undergo attack at the 6,7-double bond in preference to the 1,2-double bond resulting in the formation of 6a-chloro-6)5,7i5-methylene-A -3-ones. ... 

Lithium-ammonia reductions of most steroidal enones of interest create one or two new asymmetric centers. Such reductions are found to be highly stereoselective and this stereoselectivity constitutes the great utility of the reaction. For conjugated enones of the normal steroid series, the thermodynamically most stable products are formed predominantly and perhaps exclusively. Thus the following configurations are favored 5a, 8/ , 9a, and in certain cases 14a (see page 35). Starr has listed numerous examples illustrating these facts and Smith " and Barton have tabulated similar data. 

Functionalization of the methyl groups in the photolysis of the nitrites of 6-hydroxy-4,4-dimethyl steroids is used as a probe for conformational analysis. It is confirmed that in the 4,4-dimethyl-19-nor-series ring A has the normal chair... 

Over the past 10 years, liquid chromatography coupled with ultraviolet detection appears to have become the method of choice for the determination of corticosteroids, offering tlie analyst both satisfactory selectivity and sensitivity. Both reversed-phase (544-547) and normal-phase (548) chromatography have been applied to the determination of dexamethasone in plasma, coupled with ultraviolet (UV) detection generally at 254 nm, and in bovine tissues (528, 535). A series of both reversed- and normal phase LC systems have also been used for the simultaneous determination of dexamethasone and other steroids. Two different liquid chromatographic separations have been described for the isolation and simultaneous separation of steroids in serum (549). 

For the puiposes of retrosynthetic analysis, a six-membered ring in a target can be related to a Robinson annulation of an existing ketone with an a,/3-unsamrated ketone. Normally cc,/3-unsaturated methyl ketones are used to facilitate the ring closure, but this is not an absolute requirement. Thus the target steroid S could potentially be constructed by a series of Robinson annulations as shown. The last retrosynthetic step (the first synthetic step) could be problematic as a mixture of regioisomers would be formed. 

Although minor, the contribution from steroid substances has been generally neglected. Figure 2 shows the compounds isolated from a sample of cholesterol irradiated at 6 megarads. The principal products were a series of normal alkanes from Ci to C7 and a series of isoalkanes from C4 to Cs. The relative abundance of the iso compounds compared with the normal compounds is shown by dashed lines. The origin of these series of compounds is readily deduced to be the result of cleavage of the alkyl side chain of the cholesterol molecule. 

Stereospecific 2,3-epoxidation of squalene, followed by a nonconcerted carbocationic cyclization and a series of carbocationic rearrangements, forms lanosterol [79-65-0] (77) in the first steps dedicated solely toward steroid synthesis (109,110). Several biomimetic, cationic cydizations to form steroids or steroidlike nuclei have been observed in the laboratory (111), and the total synthesis of lanosterol has been accomplished by a carbocation—olefin cydization route (112). Through a complex series of enzyme-catalyzed reactions, lanosterol is converted to cholesterol (2). Cholesterol is the principal starting material for steroid hormone biosynthesis in animals. The cholesterol biosynthetic pathway is composed of at least 30 enzymatic reactions. Lanosterol and squalene appear to be normal constituents, in trace amounts, in tissues that are actively synthesizing cholesterol. 

The Hofmann fission of quaternary ammonium salts displays some unusual features in the steroid field. The elimination is normally of E2 character, and in acyclic structures gives olefinic products according to the familiar Hofmann rule [ 14]. The behaviour of 3-trimethylammonium steroidal salts is unexceptional [32, 3 ] the axial 3u compounds in the 5a-series giving A -olefins (5), or in the case of compounds already unsaturated at C-C 6) (6), the A -dienes (7). The 3j8-trimethylammonium-5a compounds are stable to bases, or... 

An instructive case of conformational frustration of a carbonyl-forming reaction has been noted in the 5, 6 -epoxy-steroid series. The normal mode of reaction, formation of a 5a-6 ketone [ >21], is prevented in 5,6 S-epoxy-4,4 dimethyl-5)9-cholestan"3-one 9), although the products (ii) and (12) [iih,c,d] arise via a C(S) carbonium ion (10), despite the polar... 

As expected, substitution by azide ion occurs more readily when the alkyl substrate bears electron-withdrawing groups. For example phenacyl bromide and its derivatives give high yields of azides when treated with sodium azide in the cold °. Secondary alkyl substrates undergo Sj,2 reactions with azide ion ° ° but with less facility than primary alkyl substrates in accordance with the normal polar influences and primary steric eflfects in reactions . Selective substitution is therefore possible and this has been effectively applied in carbohydrate and steroid synthesis (sections II.B.5,6). These effects are also exemplified in the alicyclic series where it has been reported that menthyl halides and 2-methylcyclohexyl halides afford unsatisfactory yields of azide ° . The unsubstituted alicyclic azides, however, are obtained in good yields by the procedures outlined above(Table 1). 

The 9(10-> l9)-abeo analogue (6) of oestrone methyl ether has been shown by X-ray crystallography to have the normal 9a -configuration, but because of the chair conformation of the enlarged ring b the molecule differs considerably in shape from oestrone methyl ether. X-Ray, n.m.r., and o.r.d. data establish the structures and absolute configurations of a series of insect-repellent steroids isolated from Nicandra physaloides. The structure and conformation of the 6-sila-steroid (7) have been determined. ... 

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