3-Cholestanone, preparation

Cholestanone has been prepared by the oxidation of dihydro-eholesterol with chromic anhydride in acetic acid solution.1 The yield is sometimes diminished as a result of the partial acetylation of the sterol. 

Nelson and Scliut investigated the reaction of 5a-cholestanone (lb) with diazomethane in a search for a direct, one-step preparation of A-homo ketones. Using a large excess of diazomethane generated in situ from A-methyl-nitrosourea with potassium hydroxide in ether-methanol at 0°, 5a-cholestanone (lb) is converted into the 7-membered ring homolog (3b) as the predominant product. Both theoretically possible A-homo ketones can be expected with an unsymmetrically-substituted cyclohexanone such as 5a-cholestanone (lb). 

A dipolar cycloaddition of a steroidal nitrile oxide to trifluoropropene, followed by reductive hydrolysis, was used to prepare the trifluoromethyl cholestanone... 

Lehn synthesised guanidinium-based cationic steroids incorporating an acylhy-drazone linker using the approach shown in Fig. 9 [141]. The synthesis was developed from a polyamine scaffold by guanidination of the primary amino groups and alkylation of the secondary amine with methyl chloroacetate to introduce the ester moiety required to form a hydrazide group by reaction with hydrazine monohydrate. Cationic steroid hydrazones were then prepared via an acetic acid catalysed reaction with cholestanones, which demonstrated high transfection efficiency and low toxicity in a variety of cell lines [141]. 

The method is useful in the preparation of other axial alcohols. Henbest6 has reported the reductions of 3-bbutylcyclohexanone, 3,3,5-trimethylcyclohexanone, and cholestanone to the axial alcohols by this procedure, although for the preparation of 3 a-cholestanol the procedure of Edward7 is preferred by the checkers. Recently8 2,4,4-trimethylcyclohexanone has been reduced to the pure axial alcohol by this method in 90% yield. 

Preparation of a-ftuoroketones and vinylogs. Gabbard and Jensen" of the Ben May Laboratory of Cancer Research converted cholestanone into the pyrrolidyl-enamine and bubbled perchloryl fluoride into a benzene solution of this derivative until an initial orange color was discharged (30 sec.). Workup and crystallization afforded 2o -fluorocholestane-3-one in good yield. Joly and Wamant" studied the... 

Dilithium derivatives 102-105 were generated by reductive opening of epoxides derived from D-glucose, D-fmctose, estrone and cholestanone, respectively, and trapped with different electrophiles. In this way, 6C-substituted 6-deoxy-D-glucose, 3C-substituted D-psycose [85], 17C-substituted-17/8-estradiol and 3C-substi-tuted-3a-cholestanol [91] derivatives were prepared. 

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