5a-Steroid

The isotopic purity of the products from a lithium aluminum deuteride reduction is usually equivalent to that of the reagent. The presence of moisture has little effect on the isotope composition of the products, causing only the decomposition of some of the reagent. For the best results, however, it is advisable to distill the solvent— usually ether, tetrahydrofuran or dioxane depending on the desired reaction temperature—from lithium aluminum hydride directly into the reaction flask. In this manner the reduction of 3-keto-5a-steroids (60), for example, gives the corresponding 3a-di alcohols (61) in 98% isotopic purity. ... 

Lithium aluminum deuteride reduction of the 2a,3a-oxide function has been carried out with a number of different 5a-steroids (227). ° The isotopic purity of the resulting 2 -d,-3a-ols (228) is usually 96-100%. By mild oxidation, under Jones conditions, these alcohols can be converted into stereospecifically labeled monodeuterio ketones (229) ° of high isotopic purity. (For an alternate preparation of certain a-monodeuterio ketones, see section VI-B.)... 

An example is the preparation of 18-trideuterio 5a-steroids bearing a side chain at C-17. Labeling of this position with three deuteriums was accomplished by utilizing the Johnson procedure for steroid total synthesis. This synthesis involves, in part, introduction of the 18-angular methyl group by methylation of the D-homo-17a-keto-17-furfurylidene intermediate (243). By substituting d3-methyl iodide in this step, the C/D cis- and ra/J5-18,18,18-d3 labeled ketones [(244) and (245)] are obtained. Conversion of the C/D tra 5-methylation product (245) into 18,18,18-d3-d /-3)8-hydroxy-5a-androstan-17-one (246) provides an intermediate which can be converted into a wide variety of C-18 labeled compounds of high (98%) isotopic... 

While the dehydrohalogenation of 3-halo-5a-steroids gives the A -olefin selectively, it has been shown that in the 5j5-series dehydrochlorination of 3j5-chloro compounds with quinoline gives a mixture of A - and A -olefins in a 45 55 ratio. 

The procedure involving a-halo ketone intermediates has been used for the synthesis of 11, 12 - and oxiranes of 5a-steroids... 

In the presence of an axial la-hydroxyl group methylmagnesium iodide reacts with 3-keto-5a-steroids from the j5-side exclusively to yield the 3f -methyl isomer. ... 

Reduction of steroid ketones. Steroid 3-ketones can be reduced selectively by potassium tri-sec-butylborohydride in the presence of 17- and 20-keto groups to the 3-axial alcohol (3a-OH for 5a-steroids 3/f-OH for 5/J-steroids). 

Jarman M, Smith HJ, Nicholls PJ and Simons C (1998) Inhibitors of enzymes of androgen biosynthesis cytochrome P450 7l, and 5a-steroid reductase. Nat Prod Rep 15, 495-512. 

Reduction of saturated l-oximino-5a-steroids with usual reagents gives the la-amino-derivatives. The previously unknown 1/3-amino-compounds have now been obtained by reduction of the A2-unsaturated 1-oxime. Hydrogenation (Pt-H2) leads to the saturated la- and 1/3-amines directly, while zinc-acetic acid gave the unsaturated amines which could be hydrogenated in a separate step to give the saturated amines.197 The four isomeric 16-azido-17-alcohols, and thence the 16-amino-17-alcohols, have been prepared by the routes indicated in Scheme 8 [3-methoxyoestra-l,3,5(10)-triene series]. The 16/3,17/3-epoxide gave a mixture of two tra/ts-azido-alcohols.198... 

Selena- and 2-tellura-A-nor-5a- (238) and 2,3-dithia-5a-steroids (239) have been obtained by treating the seco-dibromide (237) with Na2Se, Na2Te, and Na2S2, respectively.205... 

Stubbs, A. P., Murphy, G. M., and Wilkinson, M. L., 1991. Isocratic high-performance liquid chromatographic measurement of optimal 5a-steroid reductase activity in Hep-G2 cells. J. Chromatogr. 570, 293-299 (1991). 

The attempted hydrogenation of double bonds at either the 7,8- or 8,9-positions in a 5a-steroid system results merely in migration of the double bond to the 8,14-position [59],... 

In a detailed study of effects of remote substituents on the rate of condensation of benzaldehyde with 5a-steroidal-3-ketones (at C(2)), Barton obtained kinetic evidence of a long-... 

SOME gEOUP rate FACTORS" FOR CONDENSATION OF BEN2ALDEHYDE WITH 5a-STEROIDAL 3-KETONES... 

Nucleophilic substitution of toluene- -sulphonates (tosy-lates) and other sulphonic esters of secondary steroidal alcohols has received much attention, both in studies of reaction mechanisms, and also as a route for the conversion of alcohols into their epimers. One of the most important practical objectives has been the synthesis of 3a-hydroxy-5a-steroids, which include androsterone and a wide variety of metabolites of the steroid hormones, Tosylates of equatorial 3jS-alcohols (15) give 3a-alcohols or their derivatives (16) in acceptable... 

Dehydrobromination of a -bromoketones by the action of nitrogenous bases, and more recently by lithium salts in iV,A -dimethylformamide, is probably of unexceptional mechanism when it leads to the simple elimination product. However, 2a-bromo-3-oxo-5a-steroids (24) tend to give abnormal products, the A -3-ketones (26) [138]. The equatorial conformation of the 2 a-bromo substituent makes it relatively un-reactive to elimination, and it has been proposed that a 1,4 -elimination from the A -enol derivative (25) intervenes to give the observed A4-3 ketone (26) in considerable yield. It is known that i,4 -elimination is stereoelectronically favoured... 

Photochemical addition of trifluoroiodomethane on to a 5a-steroidal-3-ene affords the novel 3a-trifluoromethyl-4/i-iodo-derivative (115). ... 

---