Cholestane synthesis

The use of thiocyanic acid for thiirane synthesis is usually compatible with many functional groups found in natural steroids. The method has found application in androstanes, pregnanes, cholestanes, cholanates and cardeno-lides. However, the presence of a,j5-unsaturated carbonyl groups may decrease the yield of the thiocyanatohydrin due to conjugate addition of thiocyanic acid. Indeed, the 1,4-addition of thiocyanic acid has been carried... 

Acetoxy-21-nor-5a-cholestan-20-one (73a) as well as the free alcohol (73b) react with methylmagnesium iodide to give a mixture of epimeric diols (74). After treatment with acetic anhydride and subsequent hydrogenation over reduced platinum oxide this mixture alfords 3j5-acetoxy-5oc-cholestane (75) which is identical with the natural product. This synthesis has been used to prepare the 21- C compound (75) in a total yield of 18... 

The position of the keto group of A-homo-5a-cholestan-3-one (5b) was determined by Nelson and Schut by an unambiguous synthesis of ketone (5b) involving bis-homologation of 2,3-seco-5a-cholestane-2,3-dioic acid (8) using the Arndt-Eistert sequence [(9) (11)]. 

Ligand 92 was readily prepared by reaction of (+)-pinocarvone with 1-phenacylpyridinium iodide. The authors similarly prepared corresponding 5,6-dihydro-1,10-phenanthrolines derived from (+)-pinocarvone and a tetrahydroquinolone (structure 93, [127]) and obtained up to 81% in the palladium-catalyzed test reaction. Chelucci et al. [ 128] reported the synthesis of chiral Ci-symmetric 1,10-phenanthrolines incorporated in asteroid backbone. Structure 94 derived from 5o -cholestan-4-one in Scheme 51, allowed very high yield and up to 96% ee using BSA and tetrabutylammonium fluoride to generate the malonate anion. 

The reaction of 3/3-acetoxy-5a-cholest-8(14)-en-7-one with EtjAlCN was the key reaction in a synthesis of cholestanes containing an oxygenated 14a-substi-tuent. Cholest-4-en-3-one reacted smoothly with KCN-acetone cyanohydrin in benzene or acetonitrile containing 18-crown-6 to give the epimeric 5-cyano-cholestan-3-ones. An 11 -hydroxy-group increased the proportion of a-epox-ide produced in the reaction of 3-oxo-A -steroids with H202-0H . A 9a-fluorine substituent also influenced the stereochemistry of the reaction products and a... 

Ketal formation is a procedure used in steroid synthesis. For example the reaction of cholestan-3-one (I) in anhydrous methanol with a trace of concentrated hydrogen chloride was investigated by Zalkow and co-workers (18). 

Alternatively, the aromatic ring of an unsubstituted phenylacetate can itself act as a carrier, apparently forming a loose complex with a chlorine atom. 5a-Cholestan-3a-yl phenylacetate with iodobenzene dichloride, irradiated in dichloromethane, gave the A9(U)-olefin in 53% yield, with no detectable A14-isomer.237 The radical-carrier principle has been used to introduce A9(1 -unsaturation in a novel synthesis of cortisone from its 11-deoxy-analogue (Reichstein s S).238... 

The major product of the reaction between the 3)8-acetoxy-la,2a-epoxy-6j8-yl mesylate (216) and HCl-ether-MeOH was established as la,2/3-dihydroxy-cholesterol and not the epoxide (217) as had previously been reported. The epimeric 2-hydroxy-3-methylenecholestanes (219) were synthesized by reaction of the epoxy-sulphones (218) with Na/Hg in methanol. The 14a-hy-droxycholestanes (220), (221), and (222) have been synthesized and the key step in each case was the Se02 oxidation of the 6-oxo-A -compound. The key step in the synthesis of 3j8,5-dihydroxy-5/3-cholestan-19-ol (223) was the HOBr addition to the 19-formyloxy-A -compound (224) which gave the 5j8-hydroxy-... 

The synthesis of various 2- and 4-oxa, -thia-, and -aza-5a-cholestanes has been reported. Attempts have also been made to introduce a phosphorus atom... 

---