Oestrone, synthesis

Full papers in this area of intramolecular chemistry have come from Kametani et al7 (oestrone synthesis) and from Borch etalJ (8-epidendrobine synthesis). There... 

CHR S(0)Me to give 2-methylthio-3-oxo-tetrahydronaphthalenes. Synthesis of a heterocyclic analogue starting from the corresponding pyrrole has been reported. Synthesis of a known intermediate for use in an oestrone synthesis starts from the homologue (51), which is subja ted to thermal elimination in the presence of 2-methylcyclopentane-l,3-dione. ... 

The follicular granulosa cells are the major site of synthesis of female steroid sex hormones the oestrogens. P-Oestradiol represents the principal female follicular oestrogen. Oestriol is produced by the placenta of pregnant females. Oestriol and oestrone are also produced in small quantities as products of P-oestradiol metabolism. 

Compounds described as the 15 -carboxymethyl derivatives (32) of oestrone and oestradiol have been described as haptens, without any evidence as to their configurations at C-15, or their homogeneity. The method of synthesis (via Michael addition of malonic ester to the 15-en-17-one) normally gives 15/8-substituted compounds. Some 15/8-carboxyethylmercaptoandrostane derivatives (33), obtained by addition of methyl 3-mercaptopropionate to androst-15-en-... 

Vollhardt used this sort of chemoselectivity in his 1977 synthesis of the female sex hormone oestrone. He needed an alkyl iodide, which could be made by reacting an anion of a bis-alkyne with ethylene oxide. 

Scheme 22 Total synthesis of oestrone through radical fragmentation...

Oestrone has been photo-oxygenated to a 1 1 mixture of the oestradienes (13 R = HOO, HO) and this transformation is a new application of photooxygenation to the synthesis of 19-norsteroids. ... 

Because of its flexibility, the Torgov synthesis (see Scheme 6) is still used quite frequently for the preparation of modified steroids. Acid cyclization of 3-methoxy-8,14-seco-oestra-l,3,5(10),9(1 l)-tetraene-14,17-dione (96) gave a mixture of the A -bisdehydro-oestrone (97) and A -dehydro-14/8-hydroxy-8a-oestrone (98). Catalytic hydrogenation of (98) afforded 3-methoxy-14 -hydroxy-8a,9)8-oestrone (99a) and 79% of 3-methoxy-14)S-hydroxy-8a,9a-oes-trone (99b). Treatment of (99b) with thionyl chloride in pyridine provided, after hydrolysis, 59% of 3-methoxy-A -dehydro-8a-oestrone (100), which on hydrogenation yielded the 8a,14)S-oestrone analogue (101). 

Although known for almost forty years, and in spite of a total synthesis of its racemate, the stereochemistry of doisynolic acid has remained in doubt. This problem has now been settled by a stepwise chemical conversion (Scheme 23) of 14)5-oestrone methyl ether (339), prepared from natural oestrone (114a), into c/s-doisynolic acid methyl ether (342). Osmium tetroxide oxidation of the enol acetate corresponding to (339) provided 16a-hydroxy-14)S-oestrone methyl ether. Subsequent periodic acid oxidation afforded the lactol (340), which upon treatment with diazomethane gave the aldehydo-ester (341). Electrochemical reduction of the aldehyde (341) afforded a methyl ester which by alkaline hydrolysis provided (-f )-ds-doisynolic acid 3-methyl ether (342), thus defining its complete stereochemistry. ... 

Oestrone methyl ether reacts at the 17-oxo-group with methoxyvinyl-lithium, giving the 17a-adduct (162). Hydrolysis afforded the 20-oxo-derivative (163), whereas oxidation (OSO4) generated the dihydroxyacetone system (164), albeit in the wrong configuration at C-17 for a corticosteroid synthesis. ... 

A novel synthesis of D-homo-oestrone (101) begins with the aldehyde (88). Conversion into (89) followed by sodamide-ammonia cyclization yielded (90), which was then transformed into (91). The second component required for the synthesis, (94), was prepared by addition of 2-methyclyclohex-2-en-l-one to vinylmagnesium bromide, the product (92) being converted by way of (93) into (94). The reaction between the compounds (91) and (94) in t-butyl alcohol containing potassium... 

A convenient synthesis of ll, 17 -dihydroxyoestra-4,9-dien-3-one starting from 17jS-hydroxyoestra-4,9-dien-3-one has been described, as have the preparations of oestr-5- and -5(10)-en-17-ones and their 7a-methyl analogues. The methyl ethers of 16a- and 16) -bromo-13a-oestrone and both 17a- and 17)S-bromo-16-ones have been prepared for conformational analysis studies and a new synthesis of 3-methoxyoestr-16-ene and its two epoxy-derivatives has... 

Another synthesis of the etiojervane analogues of testosterone and oestrone has appeared. ... 

CarbocycUc Steroids.— The Torgov synthesis continues to exhibit its great versatility and was recently employed in the first synthesis of B-homo-oestrone. Condensation of the vinyl alcohol (407) and 2-methy 1-cyclopentane-l,3-dione in the presence of l,4-diazabicyclo[2,2 ]octane and cyclisation with toluene-p-sulphonic acid gave the B-homo-oestrapentaene (409) in 33 % overall yield from 3-methoxybenzosuberone. A three-stage reduction by sodium borohydride, catalytic hydrogenation, and lithium-ammonia afforded 3-methoxy-B-homo-... 

Further application of the Torgov reaction has been made in the synthesis of oestrone, the 3,16-dimethylether of oestriol, and a series of 4-halogeno-oestrogens. A novel modification involves the use of allylic amine (412) (readily prepared from the enamine of m-methoxytetralone) in place of the usual alcohol... 

A synthesis of the 8,13-diaza-oestrone (477) via cyclisation of (476) has been described.Condensation of the -diketone (479), obtained by alkylation of the morpholine enamine of 6-methoxytetralone, with guanidine carbonate or hydrazine has been used to prepare the 11,13-diaza-steroids (480) and (478) respectively (see Scheme 8). 

The supply of oestrogen produced endogenously for the continued maintenance of tumour growth may be supplemented by the cancerous tissue itself (see review by Miller [30]). Over half [31] of human breast cancer cells synthesize oestrogen from androgen precursors in vitro [32-35]. Studies [35] on the synthesis in situ of oestrogens from human breast tumours by either the aromatase enzyme (from androstenedione) or a sulphatase enzyme (from oestrone sulphate) have shown that the latter pathway predominates. The sulphatase laromatase activity ratio is about 10 at normal in vivo concen-... 

Investigation of the temperature dependence of the photochemistry of o-methylacetophenone has revealed that the rate of decay of the biradical generated in the photoenolization is associated with a low A factor. An explanation for the effect lies in the requirement for spin inversion in the process. The key step in a newly developed synthesis of ( )-oestrone is the photoinduced cyclization (1) (2). Excitation of (1) induces photoenolization to the kinetically... 

Johnson and co-workers (1958, 1962) have carried out a total synthesis of oestrone each step in their synthesis was stereoselective, but Hughs and co-workers (1960) have put forward a total synthesis of oestrone which appear to be comparatively simpler than any other previous method. 

Hugh s total synthesis of OESTRONE from l-(3-methoxy)-phenyl propyl bromide offers a comparatively simpler method than others. Explain. 

---