Steroids, coplanarity

A variety of conditions has been used to prepare oxiranes from trans-hxomo-hydrins. In general, bromohydrins are heated in a solution of 5-10% methanolic potassium hydroxide for 30 min to 8 hr. Longer reflux times are required for bromohydrins which are not anti-coplanar, e.g., diequatorial bromohydrins. A 5 % solution of potassium acetate in boiling ethanol can be used to cyclize steroidal bromohydrins containing base sensitive groups. The use of 1.1 equivalents of sodium methoxide per equivalent of steroid in methanol solution is especially recommended for 9a-bromo-l lj5-hydroxy steroids. 

The steroid skeleton in question differs from the all-fran -fused system only in respect of ring A, which has an unsaturated ketone. Because of the coplanarity of bonds in this system, there will be some distortion in ring A, which can be represented (approximately) as shown. 

Many steroid alcohols are readily converted into olefins by thionyl chloride or phosphorus oxychloride in pyridine. It has been amply demonstrated that the reaction involves stereospecific loss of an a i -coplanar proton, even if this results in formation of the less stable of the possible olefins. The reaction is thought to proceed through intermediate chloro-sulphite or dichlorophosphate esters, which suffer base-catalysed removal of a fraws-vicinal proton. 

These electrons, according to the particular reaction involved, may come from the or-bond between the third and fourth atoms of the system, when the over-all reaction will be one of elimination or rearrangement, or from a non-bonding orbital (lone-pair) associated with the fourth atom, when the product will be a cyclic derivative such as an epoxide. The generality of this "iSMi -coplanar principle is well illustrated in reactions of steroids (see especially Chapters 3, 5, 6 and 8), and there are very few exceptions. 

Formulating the first intermediate as a Cpa) carbonium ion is an unwarranted over-simplification, for the reaction is specific for a i2j5 configuration of the original steroid derivative. Acetolysis of a i2jS-mesylate displayed a very dramatic rate acceleration by comparison with the I2a-mesylate [108] the half-lives of the and i2a-compounds at 65 were respectively 8.6 min, and 39.7 h, in acetolyses kinetically of first order. Molecular models reveal an anti coplanar relation-... 

Diverse chemicals have been reported to affect measured endpoints of fish thyroidal status. These chemicals include aromatic hydrocarbons, planar halogenated aromatic hydrocarbons (dioxans, furans, coplanar PCBs), organochlorine, organophosphorus and carbamate pesticides, chlorinated paraffins, cyanide compounds, methyl bromide, phenol, ammonia, metals (aluminum, arsenic, cadmium, lead and mercury), low pH conditions, environmental steroids and a variety of pharmaceutical agents. For the following reasons their modes of action appear complex and are poorly understood16. 

The traditional depiction of the steroid system as having all four rings, A,B,C, and D, coplanar or flat is, of course, convenient, but misleading. A more representative description is given next as two forms. One represents the 5 a-steroids where the A/B ring juncture is trans so that the 5-substituent, in this case a H, is oc and therefore trans to the CH3 bonded to C-10 (but is itself 19), while the other is the 5-( series, where the A/B geometry is cis and the 5-H therefore has the P-configuration. 

The relative reactivities of two diastereomeric vicinal dibromide derivatives of cholanic acid also provided evidence for an anti-coplanar orientation of the two carbon-bromine bonds in iodine-promoted dehalogenation. In the lla,12)3-dibromo compound 20, each of the two bromine atoms is held in an axial conformation by the rigid steroid skeleton. On the other hand, each of the two bromine atoms is held in an equatorial conformation in the llj8,12a-dibromo isomer 21. As a result, the conformation of the Br—C—C—Br grouping is anti in 20 but is gauche in 21. When treated with sodium iodide in acetone, 20 underwent debromination readily, while 21 was unreactive under the same conditions. 

The conformational relationship of the bromine atoms is clear in 20 and 21 because of the rigidity of the steroid structure. Individual cyclohexane rings usually have considerable conformational mobility, however, and trans-1,2-dihalocyclohexanes exist as a mixture of diaxial and diequatorial conformers (Figure 10.40). While the diequatorial conformer is expected to be ttie major conformer, the anti-coplanar elimination suggested in Figure 10.39 must occur from the minor diaxial conformer. In the case of cis-l,2-dihalocyclohexanes. 

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