Cholestanyl acetate

Activation of hydrogenation catalysts. An isolated steroid 5,6-double bond possesses only low-order reactivity, for example, it adds difluorocarbene but not dichloro-or dibromocarbene. Hydrogenation of cholesterol with ordinary catalysts stops far short of completion, but Hershberg et al. found that perchloric acid has a powerful activating effect. Cholesterol (1250 g.), which had been purified by careful crystallization from ethyl acetate, was dissolved in 17 1. of ethyl acetate, 25 g. of platinum oxide catalyst and 2.0 ml. of 71% perchloric acid were added, and hydrogenation was conducted at 40-50° and 15 p.s.i. pressure. The reaction was complete in. 0 min., and pure cholestane-3/3-ol was obtained in total yield of 88%. By-products, accounted for in the yields indicated, were coprostanol ( 8-addition), cholestane (hydrogenolysis), and cholestanyl acetate (ester interchange with the solvent). 

Aliphatic ethers are cleaved by acetic anhydride containing boron trifluoride etherate plus lithium iodide at 20° 22 the alcoholic parents of the ether are obtained as main products, together with small amounts of olefin for instance, cyclohexyl acetate and 3/S-cholestanyl acetate are formed from alkoxycyclohexanes and 3/S-alkoxycholestanes, respectively. 

Remote functionalization of steroids (4,264-265 5,352-353). Breslow et al have modified their earlier procedure for chlorination of steroids at C9 or Ci4 by use of an external source of chlorine radicals, lodobenzene dichloride or sulfuryl chloride. Thus irradiation of the m-iodobenzoate of 3a-cholestanol (1) and lodobenzene dichloride in methylene chloride for 28 min. at 25° followed by saponification and acetylation leads to a mixture of 3a-cholestanyl acetate (18.4%) and the acetate of A -cholestene-3a-ol (2, 66%). Application of the... 

In the course of carrying out the benzophenone photochemistry described in the previous section, we noted that the use of CCI4 as solvent led to the formation of some chlorinated steroid products. Therefore we examined such halogenations further [36], and found that the simple free-radical chlorination of cholestanyl acetate with phenyliodine dichloride afforded the 9-chloro- and 14-chlorosteroids as the major products. Similar results were seen in bromination by bromotrichloromethane. We extended such selective radical halogenations to suppress reactions other than at C-9 and C-14 by appropriate substituent effects, but more significantly we used tethers to achieve essentially complete selectivity in the halogenations [36]. 

Androsterone (m.p. 185°C) is anatnrally occurring androgen that may be isolated from male urine. It can also be synthesized from epi-cholestanyl acetate as given below ... 

Androstane is converted in glacial acetic acid (CH3CO2H/CH2CI2 = 3 2, i = 40mAcm", T = 20°C, Pt electrode) to 17% androstanyl acetate (19) and 38% androstane is recovered. Remarkable is the selectivity of the oxidation It was found that the 6-, 7- and 12-acetates are formed in the ratio 35 1 2.5, and no other acetates could be detected. Cholestane affords 15% cholestanyl acetates the 6-, 7- and 12-acetates are formed in the ratio 40 1 2. 

A unique and surprisingly efficient synthesis of la-hydroxycholesterol has been described by Mihailovic and co-workers 114). The 5a-hydroxy-cholestanyl acetate (100), obtainable in high yield from cholesterol, was converted by irradiation with visible light in the presence of mercuric oxide and iodine into the 5,10-secosterol (101). Irradiation of (101) with a high pressure mercury lamp resulted in intramolecular cyclization to give the oxetane (102) as the major product. Treatment of this material with hydroiodic acid in acetic acid afforded la-hydroxycholesterol 3-acetate (103) in 20% overall yield from cholesterol. 

Chlorophyll, 295 Chlorotil s, 135, 140 m-Chlorotoluene, 182,183 Chloitoluron, 292 Chlorzoxoneacetaminophen, 264 4 -Cholettenone, 74 Cholestanyl silica, 158 Cholesterol, 283, 295 Cholinesterase, 293 Chromatographic enzyme reactor, 291 Chrysene, 69, 105, 107 Cinnamic acid, 293 Cinnamyl acetate, 198 Cinnamyl alcohol, 198 Cinnamyl aldehyde, 198 dausius-Mosotti fimction, 208 Qindamycin, 297 Clonazqmm, 195 Clusters of hetaeron, 250 Coating of polar adsoibent by polar solvent, 86... 

Hydroxylation of C—Hbonds. The reaction of cholestanyl xanthate (1) with Fe(C104)2 in acetic acid at 120° and in the presence of Fe(III) affords the diacetate 2 in 45% yield. In the absence of Fe(III), the yield of 2 is 34%. No oxidation of the tertiary hydrogen at Cs is observed. The xanthate probably serves as a ligand for an active iron-oxygen intermediate, which specifically oxidizes the axial hydrogen at Ci. 

Scheme 9. Dimerization of the cholestanyl amino oxime 16 and epoxy acetate 17.

The initial application of this chemistry with cesium acetate involved heating in dry DMF under an inert nitrogen atmosphere for 24-48 h in high yield for simple mesylates. However, a large amount (17%) of elimination product was found from the mesylate of 3/3-cholestanyl. Still, this preliminary study showed the promise of cesium acetate for this fundamental transformation to produce acetates from mesylates in high yield under relatively mild reaction conditions. 

Acetoxy - 5,6 - seco - 5 - oxo -6 - cholestanecarboxylic acid azide dissolved in dimethyl-formamide on a steam bath, and heating continued until Na-evolution ceases after ca. 5 min. 3j -acetoxy-5,6-seco-5-oxo-6-nor-7-cholestanyl isocyanate (Y 85%) hydrogenated 2 days with Pt-catalyst in glacial acetic acid 3/ -acetoxy-6-aza-cholestane (Y 86%) dissolved in abs. ether, treated with ethereal 1 M hypochloric acid, after 5 min. shaken with ice-cold 0.5 N H2SO4, then with 0.5 N NaOH 6-aza-cholesterol (Y 79%). 

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