Equilenin derivatives

Dehydrogenation of equilins to equilenins The equilin derivative (1) is dehydrogenated to the equilenin derivative (2) when refluxed in toluene with sodium bis-(2-methoxyethoxy)aluminum hydride. If lithium aluminum hydride... 

Syntheses via Diacids. Several variants of the total synthesis of equilenin derivatives are known in which the intermediate products are tricyclic diacids formed, in their turn, by the cyclization of oj-naphthyl-substituted long-chain keto acids (Scheme 15 see also Schemes 6 and 7). 

A longer route for the synthesis of equilenin derivatives [278] consists in the successive condensation of the bromide (3) with sodiomalonic ester and the half-chloride of succinic acid. The ketotriester (162) obtained is cyclized into the tricyclic triester (163), which, on hydrogenation, saponification, and decarboxylation, gives the diacid (164). The cyclization of its anisyl ester with subsequent acid hydrolysis leads to 18-norequilenin (165), identical with the product obtained by a total synthesis of the AB D C type (Scheme 31). 

The second group of syntheses effected via ABD derivatives linked by a Cg—Ci4 bond was first proposed, also by Robinson, in 1938 [374]. In these syntheses, ring C is formed by the cyclization of acids of the type of (270) (Scheme 26) obtained, in their turn, from the y-diketo acids (268) with an aromatic substituent comprising rings A and B and a side chain comprising atoms Cij—C17. This method leads directly only to equilenin derivatives, but the reduction of these has enabled some derivatives of estrone to be obtained. 

The A-ring of the 17-ol (25) derived from equilenin 3-methyl ether is reduced rapidly under Birch reduction conditions, since the 1,4-positions are unsubstituted. The B-ring is reduced at a much slower rate, as is characteristic of aromatic compounds in which 1,4-reduction can occur only if a proton enters an alkylated position. Treatment of (25) with sodium and t-butyl alcohol in ammonia reduces only the A-ring to afford the corresponding 1,4-dihydro compound in over 85% yield.On the other hand,... 

This procedure was used for the asymmetric total synthesis of the steroid (+)-equilenin (7-7) [3]. Cyclopropylidene derivates 7-4 could be converted into the cyclobutanones 7-5 in good yields by applying an asymmetric epoxidation using the chiral (salen)Mnm complex 7-6 (Scheme 7.2) [4]. It is of interest that the demethoxy-lated substrate 7-4b led to 7-5b with a very high enantiomeric excess of 93%, whereas 7-4a gave 7-5a with only 78% ee. 

Furan-2-methanols are cleaved to derivatives of levulinic ester by methanolic hydrogen chloride a mechanism involving the carbonium ion (375) has been proposed. Under similar conditions, a,(3- unsaturated carbonyl compounds of type (384) undergo a similar rearrangement, a reaction known as the Marckwald rearrangement, and afford keto esters of type (385), as shown in Scheme 105 in an example drawn from a synthesis of equilenin (70AJC547). 

The seco-steroids (327) were obtained by dehydrogenation, cleavage and aro-matization occurring during treatment of oestradiol derivatives with DDQ. Treatment of oestrone (114a), equilenin, and isoequilenin acetates with peracids afforded the lactones (328), (329a), and (329b), respectively. When heated... 

Modification of the BINAP framework provides a viable alternative approach to structural fine tuning. An ingenious synthesis which obviates the need for a resolving agent is to replace 2-naphthol with a derivative of the steroid equilenin (Fig. 42). The ligand is then isolated by a chromatographic separation of diaster-eomers, since the biaryl coupling reaction produces both the and S x forms... 

The classical work of Butenandt and Doisy on the isolation of the estrognic hormone, estrone in 1929 from pregnancy urine was aided by much preliminary biological work, the introduction of important bioassay methods by Allen and Doisy in 1923 and Ascheim and Zondek and the involvement of the company Sobering AG. The structure was elucidated through the work of several different groups on the synthesis of numerous degradation products. Estrone and its derivatives from such natural sources were soon introduced into therapy. The first synthesis of a steroid, namely the naphthalenic relative equilenin (3)... 

IV-Tosyliminoiodanes, ArINTs, have found synthetic application as useful nitrene precursors in transition metal catalyzed amidation of saturated C—H bonds in various organic substrates. Breslow and coworkers have developed the regioselective amidation of steroidal derivatives catalyzed by metalloporphyrins [690,691]. Specifically, the aromatic steroid equilenin acetate 657 undergoes regioselective and stereoselective amidation catalyzed by a manganese porphyrin using PhINTs as the nitrene donor (Scheme 3.261) [690],... 

Estrone, equilin, equilenin, and their 17-a diols have been assayed in natural and synthetic raw materials and pharmaceutical formulations after acidic hydrolysis of the sulfate derivatives (70). The method includes a two dimensional separation of the steroids on a high perfiMmance silica layer with cycldiexane-chlorofinrm-methanol-ttietfaylamine (80 90 10 15, v/v), arid chlwofmm-dioxane-trieth-ylamine (1000 75 50, v/v) as mobile phases fw the first and second devdtqnnents, respectively. Excellent selectivity and reproducibility were rqKxted. 

A series of 9,11-seco-11-hydroxy and 11-carboxylic acid derivatives of equilenin were synthesized. It is noteworthy that of the four isomers tested, only that one which corresponds to the 13-epimer of the natural hormone has any significant estrogenic activity. A very flexible B,C-bis-seco estrone derivative (15) was prepared and found to have only very weak estrogenic activity (ca. T/250 x estrone).55... 

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