Androstan-3,17-dione

Reactions of 5a- and 5/3-androstane-3,17-diones with ozone in HF-SbFj gave directly the 6-oxo- and 7-oxo-compounds. Some epimerization of the 5j8-6-oxo-... 

Henbest reduction (see Chloroiridic acid). Substitution of chloroiridic acid by tris(triphenylphosphine)chlororhodium results in even greater stereospecificity thus 5/3-androstane-3,17-dione is reduced to the 3/3-alcohol and 3 -alcohol in the ratio 50 1, with no detectable reduction of the 17-keto group. The reaction is preferably run in a sealed tube t 82°. 2-Ketosteroids are reduced entirely to the axial 2/3-alcohol (Henbest s conditions give 1% of the 2a-alcohol).1... 

Ap-54 Noguchi, S., and Fukushima, D. K., J. Org. Chem. 30, 3552 (1965). Penicillium sp. with 3a-hydroxy-5a-androstan-17-one gave 12 -hydroxy product. The same organism with 3/S-hydroxy-5o-androstan-17-one gave the la-hydroxy product and with 3/3-hydroxy-50-androstan-17-one gave the 7 -hydroxy product and 7/ -hydroxy-5/3-androstane-3,17-dione. 

Testosterone is metabohzed in the liver to androsterone and etiocholanolone (Figure 58-3), which are biologically inactive. Dihydrotestosterone is metabolized to androsterone, androstane-dione, and androstanediol. 

In a study by Albaum and Staib (1965) 4-androstene-3,17-dione was incubated with reduced nicotinamide adenine dinucleotide phosphate and liver microsomes which had been prepared from normal rats. The following metabolites were demonstrated by infrared spectroscopy 7a-hydroxy-4-androstene-3,17-dione,6) -hydroxy-4-androstene-3,17-dione, and androstane-dione. Another metabolite was very likely identical with testosterone. Differences due to sex were observed in the formation of the various metabolites. 

The 11-keto group is relatively difficult to attack, due to steric hindrance. However, reaction of 3j -hydroxy-5a-androstane-l 1,17-dione (37) with methylmagnesium bromide at 25° unexpectedly gives a 30% yield of 1 la,17a-dimethyl-5a-androstane-3j5,lljS,17i -triol (38) in addition to the 17-monomethyl product (39). 

An ethereal solution approximately 2.5 molar in methyllithium is prepared from 17 ml of methyl iodide and 4 g of lithium metal in 200 ml of anhydrous ether. A mixture consisting of 150 ml anhydrous ether, 3 g (10 mmoles) of 3jS-hydroxy-5a-androstane-ll,17-dione and 60 ml (0.15 moles) of the above methyllithium solution are stirred at room temperature for 40 hr. The reaction mixture is diluted with 100 ml of water and the ether is removed by distillation. Filtration of the chilled aqueous phase yields 2.6 g (77%) of 1 la,17a-dimethyl-5a-androstane-3a,l l/ ,17j5-triol mp 149-154°. Recrystallization from acetone-hexane yields pure material mp 164-166° [a] —5° (CHCI3). 

With 3a-hydroxy-5a-androstane-ll,17-dione acetate (99) a mixture of 17a- (101) and 17-D-homo ketones (102) is obtained in a 1 to 6 ratio. 

The many hormone analogs prepared in the 10(54)uZ)eo-estr-4(10)-ene-3,5-dione and the 10(54i H)uZ)eo-androstane-3,5-dione series clearly demonstrates that a wide range of functional groups may be safely carried through these synthetic sequences or that the resulting products have the requisite functionality for further structural elaboration. 

P-Acetoxy-5, l-diketo-5,6-seco-androstan-6-oic Acid (77). To a solution of dione (76) dissolved in 50 ml of chloroform in a water bath is added, in portions with stirring over 0.5 hr, 7.5 g of m-chloroperbenzoic acid - (assay 85%). The mixture is stirred at room temperature for about 18 hr and then evaporated in vacuo at 25° to give a mixture of m-chlorobenzoic acid and 3y5-acetoxy-5,17-diketo-5,6-seco-androstan-6-oic acid. The mixture can be used in the following step with only a small loss in overall yield. ... 

Acetoxypregna-5,16-dien-20-one, 211 3/3-Acetoxy-5a-pregnane-l 1,20-dione, 207 3 a-Acetoxy-5/3-pregnane-20-one, 178 3/3-Acetoxypregn-5-en-20-one, 71 3 /3-Acetoxypregn-5-en-20-one-[l 7 a, 16a-c]-A -pyrazoline, 106 3/3-Acetoxy-5a-pregn-9( 1 l)-en-20-one-[17a, 16a-c]-Ai-pyr azoline, 106, 107 17/3-Acetoxy-2,3-seco-5a-androstan-2,3-dioic acid, 409... 

Androsta-4,9 (11) -diene-3,17-dione, 150 Androsta-5,16-dien-3 -ol, 33 Androstane-3, 6/3,17 -triol 3, 17-diacetate, 244... 

Dibenzoy loxy-7 a, 8a-methylen-5a,8a-androstan-6a-ol, 113 Dibromocarbene, 366, 367, 372 1,4-Dichloro-2-butyne, 68 Dichlorocarbene, 364 9a,l 1 -Dichloroandrosta-1,4-diene-3,17-dione, 150... 

Androstene-3,l 7-dione and other androstane and testosterone-related steroids are often also produced. 

CijHijBrOj 24085-07-2) see Salbutamol l-[4-(acetyloxy)-3-[(acetyloxy)methyl]phenyl]-2-[(l,l-di-methylethyl)(phenylmethyl)amino]ethanone (C24H29NO5 77430-27-4) see Salbutamol l-[4-(acetyloxy)-3-[(acetyloxy)methyl]phenyl]ethanone (C13H14O5 24085-06-1) see Salbutamol lV-[(3P)-3-(acetyloxy)androsta-5,16-dien-17-yl]acetamide (C23H33NO3 65732-71-0) see Prasterone (5a,17P)-17-(acetyloxy)androstane-l,3-dione cyclic 3-(l,2-ethanediyl acetal)... 

It is worth noting that we have previously observed a sharp increase in the amount of the axial epimer when reducing 5a-androstan-3,17-dione with 2-... 

Scheme 20.22 The reduction of androstan-3,17-dione (71) using an iridium catalyst.

This enzyme [EC 1.1.1.50], also referred to as hydroxy-prostaglandin dehydrogenase, catalyzes the reaction of androsterone with NAD(P)+ to produce 5a-androstane-3,17-dione and NAD(P)H. Other 3a-hydroxysteroids can act as substrates as well as 9-, 11- and 15-hydroxy-prostaglandins. The stereochemistry is B-specific with respect to the pyridine coenzymes. 

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