Diols, steroidal

Chiraldex G -PH Cyclic and bicyclic diols, steroids and earbohydrates. 

N H2SO4 added to a soln. of 1 g. 20a-acetylamino-5a-pregnane-3y, 18-diol in methanol, and refluxed 2 hrs. 0.92 g. 20a-amino-5a-pregnane-3, 18-diol. — Steroidal acetylamines are very stable and may resist hydrolysis by the usual methods. L. Labler and F. Sorm, Coll. 24, 2975 (1959). 

A number of steroids have been regioselectively acylated ia a similar manner (99,104). Chromobactenum viscosum hpase esterifies 5a-androstane-3P,17P-diol [571-20-0] (75) with 2,2,2-triduoroethyl butyrate ia acetone with high selectivity. The hpase acylates exclusively the hydroxy group ia the 3-position giving the 3P-(monobutyryl ester) of (75) ia 83% yield. In contrast, bacillus subtilis protease (subtihsia) displays a marked preference for the C-17 hydroxyl. Candida iylindracea]i 2Lse (CCL) suspended ia anhydrous benzene regioselectively acylates the 3a-hydroxyl group of several bile acid derivatives (104). 

The hydrogenation of ring A aromatic steroids over ruthenium occurs, almost invariably, from the a side and all substituents on the original aromatic ring are cis in the resulting cyclohexane. Estrone (62) is hydrogenated over ruthenium to 5a,10a-estrane-3/3,17j6-diol (63) in 85-90% yield. 

Although lead tetraacetate can attack many polar and nonpolar functions in the steroid molecule, its greatest reactivity is towards vicinal diols. These diols are generally cleaved so rapidly under stoichiometric conditions that other alcohol functions in the molecule need not be protected. Thus lead tetraacetate in acetic acid at room temperature splits the 17a,20-diol group in (9) to yield the 17-ketone (10), the allylic A -3jS-alcohol remaining intact during this oxidation. Since lead tetraacetate is solublein many anhydrous... 

Disulfonate esters of vicinal diols sometimes undergo reductive elimination on treatment with sodium iodide in acetone at elevated temperature and pressure (usually l(X)-200°). This reaction derived from sugar chemistry has been used occasionally with steroids, principally in the elimination of 2,3-dihy-droxysapogenin mesylates. The stereochemistry of the substituents and ring junction is important, as illustrated in the formation of the A -olefins (133) and (134). 

Steroidal cis vicinal diols at the 1,2-, ° 2,3-, ° 5,6- or 11,12- " positions can be selectively protected as acetonides, prepared by reaction with acetone at room temperature or at higher temperatures in the presence of hydrochloric, perchloric or -toluenesulfonic acids. Cis nonvicinal-diols can be similarly protected. 

The Simmons-Smith reaction has been used to great advantage in the conversion of 19-nor steroids to the naturally occurring 10)5-methyl steroids as well as the unnatural lOa-methyl steroids. Thus methylenation of androst-5(10)-ene-3a,17 -diol (9) proceeds in an autoclave at elevated temperatures with stereospecific a-face addition to give the 5a,10a-methylene compound (10) in 85% yield. 

Hydrolysis of 6p,l9-Oxido-3a,5a-cyclo steroids.A solution of 0.1 g of 3a,5a-cyclo-6)5,19-oxidocholestane in 20 ml of acetone is treated with 1.0 ml of water and 0.5 ml of 1 N sulfuric acid. After standing for 2 hr at room temperature, the solution is neutralized with saturated sodium bicarbonate solution and extracted with ether. The combined ether extracts are washed with water and concentrated to dryness under reduced pressure. Recrystallization of the crude product from methanol yields 85 mg choIest-5-ene-3, 19-diol mp 147-149° [aj —30°. 

A-Nor-B-homo steroids with different substitution patterns than those described above may be prepared by acid catalyzed cyclization of 3)3-hydroxy-5(10)-seco-cholest-tra/w-l(l0)-en-5-one acetate (134a) formed in 30-40% yield by mercuric oxide-iodine sensitized irradiation of cholestane-3j3,5a-diol... 

Ring A contracted-ring B expanded steroids of varied complexity ranging from 10(54j9H)uZ>eo-cholestan-5-one (137) to 5(10-> l)SH)flZ)eo-cholest-10(19)-ene-3j5,5a-diol 3-acetate (135) can be prepared by one of the four methods described above. In each case, the requisite starting materials can be obtained from available starting materials by way of well-developed procedures. In view of the complexity and uniqueness of the structures thus obtainable the yields must be considered acceptable. 

Acetylenedimagnesium bromide, 66, 84, 137 Acyl-alkyl diradical disproportionations, 299 Acyl-alkyl diradical recombination, 296 Alkaline hydrogen peroxide, 10, 12, 20 Alkylation of formyl ketones, 93 Alkylation via enolate anions, 86 17a-Alkynyl steroids from 17-ketones, 67 2a-Al]yl-17jS-hydroxy-5a-androstan-3 -one, 9 5 Allylic acetoxylation, 242 Allylmagnesium bromide, 64 17 -Aminoandrost-5-en-3 -ol, 145 17 a-Aminomethy 1-5 a-androstane-3, 1718-diol, 387... 

One of the first uses of the allylic sulfoxide-sulfenate interconversion was made by Jones and coworkers64, who reported exclusive suprafacial rearrangement of the allyl group in the steroidal sulfoxide 17 shown in equation 13. Two other examples are shown in equations 1465 and 1566. Evans and coworkers have demonstrated the utility of the suprafacial allylic sulfoxide-sulfenate rearrangement in a new synthesis of the tetracyclic alcohol 24 (equation 16)67, as well as in a synthesis of prostaglandin intermediates as shown in equation 1768. The stereospecific rearrangement of the unstable sulfenate intermediate obtained from the cis diol 25 indicates the suprafacial nature of this process. 

Zheng, W.B., Strobeck, C., and Stacey, N. (1997). The steroid pheromone 4-pregnen-17 alpha, 20 beta-diol-3-one increases fertility and paternity in goldfish. Journal of Experimental Biology 200, 2833-2840. 

A combinatorial approach for biocatalytic production of polyesters was demonstrated. A library of polyesters were synthesized in 96 deep-well plates from a combination of divinyl esters and glycols with lipases of different origin. In this screening, lipase CA was confirmed to be the most active biocatalyst for the polyester production. As acyl acceptor, 2,2,2-trifluoroethyl esters and vinyl esters were examined and the former produced the polymer of higher molecular weight. Various monomers such as carbohydrates, nucleic acids, and a natural steroid diol were used as acyl acceptor. 

An unusual reaction was been observed in the reaction of old yellow enzyme with a,(3-unsat-urated ketones. A dismutation took place under aerobic or anaerobic conditions, with the formation from cyclohex-l-keto-2-ene of the corresponding phenol and cyclohexanone, and an analogous reaction from representative cyclodec-3-keto-4-enes—putatively by hydride-ion transfer (Vaz et al. 1995). Reduction of the double bond in a,p-unsaturated ketones has been observed, and the enone reductases from Saccharomyces cerevisiae have been purified and characterized. They are able to carry out reduction of the C=C bonds in aliphatic aldehydes and ketones, and ring double bonds in cyclohexenones (Wanner and Tressel 1998). Reductions of steroid l,4-diene-3-ones can be mediated by the related old yellow enzyme and pentaerythritol tetranitrate reductase, for example, androsta-A -3,17-dione to androsta-A -3,17-dione (Vaz etal. 1995) and prednisone to pregna-A -17a, 20-diol-3,ll,20-trione (Barna et al. 2001) respectively. 

Cyclic diethylsilylene and di-tert.-butylsilylene derivatives have been used to protect diol groups in steroids and prostanoids [539-541]. N,0-bis(diethylhydrogensilyl)trifluoro-methylacetamide simultaneously converts Isolated hydroxyl groups to the diethyllu ogensilyl ether allowing a single step derivatization toVp used for the analysis of corticosteriods. 

Reaction of estrone (2) with an excess of the lithium reagent from 3-iodofuran gives intermediate diol 3. The stereochemical assignment follows from the well-known propensity of steroids for attack from the less-hindered backside (a) of the molecule. Acylation of 3 with acetic anhydride then affords the estrogen estrvfurate (4).1... 

An early example of this strategy is the palladium black catalyzed conversion of (Z)-2-buten-l,4-diol with primary amines (cyclohexyl amine, 2-aminoethanol, -hexyl amine, aniline) at 120 °C to give A-substituted pyrroles in 46-93% yield [119]. Trost extended this animation to the synthesis of a series of AT-benzyl amines 169 from the readily available a-acetoxy-a-vinylketones 168 [120]. This methodology allowed for the facile preparation of pyrrolo-fused steroids. 

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