Estrone derivatives

The two synthetic steroidal estrogens which have attained the greatest degree of therapeutic use are ethinyl estradiol [57-63-6] (EE) (5) and its 3-methyl ether, mestranol [72-33-3]((5). In contrast to the naturally occurring estrone derivatives, these acetylenic analogues are orally active and are the main estrogenic components of combination oral contraceptives (see Contraceptives) and certain estrogen replacement products. 

Other examples of irreversible derivatization on treatment with iodine have been described for phenohc steroids (estrone derivatives [256]), morphine [257] and 23 other pharmaceuticals [258]. These reactions are probably favored by the presence of silica gel as stationary phase and by the influence of light. 

Estrone derivatives Silica gel GF254 lodination to 2-iodoestrone and 2,4-diiodoestrone [12]... 

A similar sequence has been utilized for an elegant assembly of the estrone derivative 68. " Under modified Heck conditions, the dibromomethoxystyrene 66 was coupled with the enantiomerically pure hexahydroindene derivative 67, prepared from an established C,D-ring building block of previously developed steroid total syntheses, under... 

Scheme 54, Synthesis of ellipticine-estrone derivative 337 by Roques and co-workers U23).

Reaction of estrone enol acetate with phenylselenenyl or methylselenenyl bromide in the presence of potassium carbonate affords 16a-(phenylseleno)- or 16a-(methylseleno)estrone derivatives l17. 

Rearrangement of phenols to dienones occurs readily in superacids. Some simple bicyclic phenols and their ethers have been investigated as model compounds by use of HF-SbFs [73]. This method is also applicable to natural products [74]. For example, treatment of estrone derivatives in HF-SbFs, then aqueous bicarbonate work-up led to estra-4,9-diene-3,17-dione (Eq. 30). The opposite rearrangement, i.e. that of dienones to phenols, can also be achieved in an HF-SbFs medium (Eq. 31) [75]. 

The use of anisoles (22) as synthetic equivalents to cyclohex-2-enones (Scheme 3) has been widespread since the original observations of Birch, and the literature is replete with examples over the past five decades, e.g. in the syntheses of steroids, terpenoids and alkaloids. The most thorough studies have been carried out within the context of the conversion of estrone derivatives to 19-norandrostane and pregnane derivatives and are instructive for the selection of reagents and reaction parameters for reductions of this general type. ... 

The reaction of estrone derivatives with HF—SbFs or FSO3FI—SbFs gives estra-4,9-dien-3,7-dione (equation 91). The intermediate tricationic species and their isomers have been characterized by H NMR spectroscopy. ... 

The following year, Djerassi and co-workers [196] utilized unimolecular decompositions to show the possibility of identifying estrone derivatives (Fig. 42), estrone (a), estradiol (b) and estriol (c). 

Numerous applications exploiting this jyri-directing effect for the stereoselective syntheses of relatively complex compounds have been reported 2. Thus, the estrone derived allylic alcohol 3-methoxyestra-l,3,5(10),15-tetraen-17a-oI is exclusively cyclopropanated from the a-side36. 

A resolved cyclopentanone acetic acid has been used in synthesis of two optically pure estrone derivatives Oppolzer,... 

Spencer, B.J. Purdy, W.C. High-performance liquid chromatographic separation of equilin, estrone, and estrone derivatives with cyclodextrins as mobile phase additives. J.Liq.Chromatogr., 1995, 18, 4063-4080... 

Removai of the methoxy group and its substitution by cyanomethyl in the protected estrone derivative shown in the form of the arene chromium tricarbonyl complex in tetrahydrofuran solution, was achieved in 46% yield by treatment at -78 C with lithioacetonitrile (from acetonitrile in tetrahydrofuran containing hexamethylphosphorictriamide and lithium di-isopropylamide at -78°C) followed by stirring for 4 hours at ambient temperature (ref. 104). 

They then found that an aromatic ring can function as the olefinic component in this rearrangement and by this route prepared the tetracyclic diketo estrone derivative 4. 

New estrone derivatives 47 and 48 containing l,2,4-triazin-5-one 34 moieties were synthesized through direct C-C coupling of estrone 3-methyl ether with triazinones (Scheme 26) <2006MC95>. 

Figure 24. Biomesogenic structures a) (Bio)meso-gens displaying order-disorder distributions in CPK-presentation (left to right and top to bottom) hexa-n-alkanoyl-oxybenzene discoid - Chandrasekar s first non-rodlike liquid crystal [28 a, 51c] enantiomeric cholesteric estradiol- and estrone-derivatives [ 17 a, c, d, 26 f, 51 a, s, u] Reinitzer s cholesterolbenzoate [21, 22] - together with the acetate the foundation stones of liquid crystal history [21, 22] Kelker s MBBA -first liquid crystal fluid at ambient temperature [ 13 f, g] Gray s cyanobiphenyl nematics for electrooptic displays [25 a, 51 e] lyotropic lecithin membrane component [7 a, 14, 27 d, 52 a] and valinomycin-K -membrane carrier [7 a, 35] thermotropic cholesteryl-side-chain-modifiedpolysiloxanes with the combination of flexible main-chain and side-chain spacers [51 a, h] thermotropic azoxybenzene polymers with flexible main-chain spacers [51a] thermotropic cya-...

The Pd(OAc)2/dppb system was applied in the cyclocarbonylation of 4-allyls-teroids for the formation of 7-membered lactone rings [84]. Based on this methodology, novel estrone derivatives were prepared in a different manner (Scheme 10.14). 

The whole protocol is illustrated in Figure S for the synthesis of an estrone derivative. At left is one of the skeletal dissections, the same as in Figure 2. The target is cut into two intermediate skeletons (A and B) at the first level, and each is cut again in two at the second level of course many other cut sequences are also found. This dissection is now retained because all four pieces (C, D, E, F) are found in the catalog in fact, at the first level, B is also a found skeleton, giving this dissection some priority. 

PKR for the synthesis of estrone derivatives, 27a and 27b.MWI was equally effective at promoting the PKR as was I-butylmethylsulfide, but that the regioselectivity was inverted. Reaction yields were improved when the target temperature was no greater than 100 °C and the alkyne was added in portions. It was also observed that reaction yields improved, in select instances, when charcoal was added to these MWI reactions. This intermolecular PKR demonstrates the regioselectivity issues observed with un-symmetrical alkene substitution. The location of the carbonyl in the products with respect to the alkene substituents is essentially random. In contrast, the alkyne substituent is only found or to the carbonyl. 

Similarly the method devised for the determination of estrone gave the 4-nitro-estrone derivative.The procedure is ... 

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... 

Example 7.27 Synthesis of an Estrone-Derived Diaryliodonium Tetrafluoroborate [96]. 

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