Androsta-l,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). 

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. 

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

The list of 4,508 names of chemicals associated with reproductive effects is given in the Appendix I to this chapter. This list could be made more practical in a shorter version, to post in the laboratory, for example. The list of 4,508 names contains many clusters of names of various derivatives of a particular compound. For example, entry 239 in the list is androsta-l,4-diene-3.17-dione, the first of 110 androstane derivatives listed in numerical order. Thus, the list could be shortened by containing only the first of the derivatives under its original entry 239. followed by the next type of compound under its entry (in this case, angiotensin II, 349). The gap between the entries would indicate the number of toxic derivatives of the foregoing entry type. A quick check of the "androsta" entry and the gap between the entries provides a chemist with the valuable information that a large number of androstane derivatives exhibit reproductive effects. 

R. Draisci, L. Palleschi, E. Ferretti, L. Lucentini, F. delli Quadri, Confirmatory analysis of 17ffboldenone, 17a-boldenone and androsta-l,4-diene-3,17-dione in... 

Androsta-l,4-diene-3,17-dione reacted selectively at C-17 with potassium acetylide to give the 17a-ethynyl-17/8-alcohol the dihydroxyacetone side-chain was then elaborated by use of known transformations, without interference from the l,4-dien-3-one system/ Ethynylation of a [16- H]- or [16- H2]-17-oxo-steroid proceeds without loss of label/ ... 

The synthesis of 1,2- (66) and 2,3-dimethoxy-4-methyloestra-l,3,5(10)-trien-17 -oI (67) from androsta-l,4-diene-3,17-dione (64) has been reported. Aroma-tization of (64) under conditions reported earlier, followed by introduction of the 17-acetate group, gave 4-methyloestratrien-17/5-ol acetate (65). Treatment of this with acetyl chloride under Friedel-Crafts conditions, followed by Baeyer-Villiger oxidation, gave access to the 1,2- and 2,3-dimethoxyoestradiol series (66) and (67). ... 

Besides cholesterol, other S. such as pregnane derivatives, bile acids, and phytosterols are also degraded, principally to androsta-l,4-diene-3,17-dione. These microbial processes have been developed in the last two decades to an industrial process for the degradation of cholesterol and sitosterol (about 100(XK) t/a of each) to androsta-l,4-diene-3,17-dione (ADD), an-drost-4-ene-3,17-dione (AD), and 9a-hydroxy-AD for use in the partial synthesis of hormonally more active S. . 

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