Androsta-1,4-diene-3,17-dione

CONTROLLED RELEASE TECHNOLOGY - PHARMACEUTICAL] pol 7) Androsta-l,4-diene-3,17-dione [63-05-8]... 

Interest in the synthesis of 19-norsteroids as orally active progestins prompted efforts to remove the C19 angular methyl substituent of readily available steroid precursors. Industrial applications include the direct conversion of androsta-l,4-diene-3,17-dione [897-06-3] (92) to estrone [53-16-7] (26) by thermolysis in mineral oil at about 500°C (136), and reductive elimination of the angular methyl group of the 17-ketal of the dione [2398-63-2] (93) with lithium biphenyl radical anion to form the 17-ketal of estrone [900-83-4] (94) (137). 

Dehydration of (105) to derivative (androsta-4,9-diene-3,17-dione [1035-69-4]) (106) provided starting material for corticosteroid synthesis... 

The rate of side-chain cleavage of sterols is limited by the low solubiUty of substrates and products and thek low transport rates to and from cells. Cyclodextrins have been used to increase the solubiUties of these compounds and to assist in thek cellular transport. Cyclodextrins increase the rate and selectivity of side-chain cleavage of both cholesterol and P-sitosterol with no effect on cell growth. Optimal conditions have resulted in enhancement of molar yields of androsta-l,4-diene-3,17-dione (92) from 35—40% to >80% in the presence of cyclodextrins (120,145,146,155). 

Ketonic carbonyl groups are commonly encountered in steroids and their reduction is facile, even in the absence of an alcohol. The lithium-ammonia reduction of androsta-l,4-diene-3,17-dione affords androst-4-ene-3,17-dione in 20% yield but concurrent reduction of the C-17 ketone results in formation of testosterone in 40% yield, even though the reduction is performed rapidly at —40 to —60° and excess lithium is destroyed with solid ammonium chloride. Similar reduction of the C-17 carbonyl group has been observed in other compounds. In the presence of an alcohol, a ketone is complete-... 

A variety of conjugated dienones are reduced by lithium-ammonia, presumably via dienyl carbanions analogous to the allyl carbanions encountered in enone reductions. Cross-conjugated l,4-dien-3-ones afford 4-en-3-ones as the major reduction products, indicating that the cyclohexadienyl carbanion (55) protonates largely at C-1. Some protonation at C-5 does occur as shown by examination of the NMR spectrum of the crude reduction product derived from the 17-ethylene ketal of androsta-l,4-diene-3,17-dione. The 17-ethylene ketal of androst-4-ene-3,17-dione is formed in 75%... 

The 17-ethylene ketal of androsta-l,4-diene-3,17-dione is reduced to the 17-ethylene ketal of androst-4-en-3,17-dione in about 75% yield (66% if the product is recrystallized) under the conditions of Procedure 8a (section V). However, metal-ammonia reduction probably is no longer the method of choice for converting 1,4-dien-3-ones to 4-en-3-ones or for preparing 5-en-3-ones (from 4,6-dien-3-ones). The reduction of 1,4-dien-3-ones to 4-en-3-ones appears to be effected most conveniently by hydrogenation in the presence of triphenylphosphine rhodium halide catalysts. Steroidal 5-en-3-ones are best prepared by base catalyzed deconjugation of 4-en-3-ones. ... 

Isolated tetrasubstituted double bonds do not react under these conditions and the saturation of trisubstituted double bonds is extremely slow, thus limiting the general utility of the method. This difference in reactivity is used to advantage for the selective deuteration of the -double bond in androsta-l,4-diene-3,17-dione (138). In homogeneous solution, saturation usually occurs from the a-side and consequently the deuterium labels are in... 

The direct reaction of androsta-l,4-diene-3,17-dione with acetylene in the presence of potassium t-amyloxide gives the 17a-ethynyl-17j -hydroxyandros-ta-l,4-dien-3-one in only 12% yield. 

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... 

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)... 

C7H,40 110-43-0) see Tuaminoheptane androsta-l,4-diene-3,17-dione cyclic 17-(l,2-ethanediyl acetal)... 

An unusual reaction was been observed in the reaction of old yellow enzyme with a,(3-unsat-urated ketones. A dismutation took place under aerobic or anaerobic conditions, with the formation from cyclohex-l-keto-2-ene of the corresponding phenol and cyclohexanone, and an analogous reaction from representative cyclodec-3-keto-4-enes—putatively by hydride-ion transfer (Vaz et al. 1995). Reduction of the double bond in a,p-unsaturated ketones has been observed, and the enone reductases from Saccharomyces cerevisiae have been purified and characterized. They are able to carry out reduction of the C=C bonds in aliphatic aldehydes and ketones, and ring double bonds in cyclohexenones (Wanner and Tressel 1998). Reductions of steroid l,4-diene-3-ones can be mediated by the related old yellow enzyme and pentaerythritol tetranitrate reductase, for example, androsta-A -3,17-dione to androsta-A -3,17-dione (Vaz etal. 1995) and prednisone to pregna-A -17a, 20-diol-3,ll,20-trione (Barna et al. 2001) respectively. 

---