25.26- Dihydroxycholesterol

Asymmetric reduction of 25-24-oxosteroids. Reduction of the unsaturated 24-oxosteroid 2 with LiAlH, and the (R)-( + )-isomer of Noyori s reagent (1) gives a mixture of the two diols 3 and 4 in the ratio 95 5. The stereoselectivity is reversed by use of (SM )-l. This reaction was used to prepare optically pure (24R)- and (24S)-24-hydroxycholcstcrol and the epimeric pairs of 24,25-dihydroxycholesterol and 25,26-dihydroxycholcsterol.2... 

Total 24S,25-epoxycholesterol calculated as the sum of 24S,25-epoxycholesterol, 24-oxocholesterol, 24,25-dihydroxycholesterol, and 24-hydroxy,25-methoxycholesterol. 

F-17(20)-dehydro-20-cyanopregnene, which may be isomerized in base to the Z-isomer. Elaboration of the side-chain by successive Grignard reaction, reduction, and removal of the 22-hydroxy-group followed. Key steps in two stereospecific syntheses of Z-20(22)-dehydrocholesterol (234) from pregnenolone were (a) stereospecific removal of the 20- and 22-oxygen atoms of (20i ,22S)-20,22-dihydroxycholesterol by conversion into the thiocarbonate (232) and treatment with triethyl phosphite and (b) selective epoxidation of iE -20(22)-dehydrocholes-teryl benzoate to the epoxides (233), which were allowed to react with hexamcthyIdisilane-KOMe in HMPA (see also ref. 179). Syntheses of the 24-... 

Fig. 5. Pattern of product formation during single turnover cycles of anaerobic reduction/oxygenation of the cytochrome P-450,.,. - cholesterol - adrenodoxin complex. The results are expressed as a percentage conversion of the total [14C]cholesterol added to the incubation. Cholesterol, o 22-hydroxy-cholesterol, 20,22-dihydroxycholesterol. a pregnenolone, (from Ref. 38, with permission).

CH(Me)(CH2)2CH=CMe2 and CH(Me)(CH2)3C(Me)=CH2. The 25-hydroxy-group was restored at the end of the synthesis. Successive acetylation, bromination, dehydrobromination, saponification, and irradiation when applied to la,25-dihydroxycholesterol convert it either into la,25-dihydroxy-previtamin D3128 or into a la,25-dihydroxy-vitamin D3,129 depending on reaction conditions. 

Totally synthetic approaches to vitamin D and its relatives are presented in the Simonsen lecture.180 Two syntheses of 25,26-dihydroxycholecalciferol have been reported and establish the 255-configuration for the natural metabolite,181-182 and the 25i -configuration182 for the previously synthesized 25,26-dihydroxycholesterol,... 

The new 23-hydroxy-epimers of cholesterol have been prepared by boro-hydride reduction of the 23-ketone, and Grignard reactions on the cyanohydrin of pregnenolone acetate have been used to prepare both epimers of 20a,22-dihydroxycholesterol. Using optically pure half-esters of methyl succinic acid in Kolbe electrolytic coupling reactions with various bile acids the corresponding 25-d- and 25-L-cholestanoic acids have been prepared. ... 

Burstein, S., B.S. Middleditch, and M. Gut (1975). Mass spectrometric study of the enzymic conversion of cholesterol to (22/ )-22-hydroxycholes-terol, (20R,22/f)-20,22-dihydroxycholesterol, and pregnenolone, and of (22R -22- hydroxycholes-terol to the glycol and pregnenolone in bovine adrenocortical preparations. Mode of oxygen incorporation. J. Biol. Chem. 250, 9028-9037. 

P450 llAl appears to be quite specific in using cholesterol as a substrate. The reaction proceeds in a three-step sequence, with generation of (22/f)-20a, 22-dihydroxycholesterol as an... 

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