Hydroxy-steroids. Part IV. The preparation and spectra of steroid olefins

Cragg, Gordon M.; Davey, C. W.; Hall, Donald N. B.; Meakins, G. D.; Richards, E. E.; Whateley, Tony L.

doi:10.1039/j39660001266

Cited by 11 publications

(7 citation statements)

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“…In the 1 H NMR spectrum of the mixture, the olefinic signals of the major olefin 14 appear as a broad singlet ( W 1/2 ≈ 5 Hz) at δ 5.59, while the corresponding signals of the minor olefin 15 resonate at δ 5.20 (br dd, J = 2.2, 10.0 Hz, 1 H) and 5.56 (m, 1 H). Similar differences in splitting pattern and chemical shift have been reported for the signals of the olefinic protons of 5α-cholest-2-ene and 5α-cholest-3-ene 4 …”

Section: Resultssupporting

confidence: 80%

Chemical Consequences of Long-Range Orbital Interactions in Cholestane-3,7-diol Monosulfonate Esters. A Seven-Center Fragmentation

et al. 1996

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The manifestation of through-five-bond interactions in the reactions of the rigid 1,5-diol monosulfonate esters (1−3), having an ideal all-trans geometry of the σ-relay, with sodium tert-amylate is investigated. It has been shown that the deprotonation of the alcohol group in 2 and 3, which results in an increased electrofugal ability of this group, finds expression in a seven-center fragmentation. This fragmentation also illustrates that effective through-five-bond interactions exist between the alcoholate group and the carbocationic center which is generated during the heterolysis. The reaction outcome of mesylate 1 does not indicate effective through-bond interactions, and only elimination is observed. This difference can be attributed to the alkyl substituents on the γ- and α-positions to the mesylate group in 2 and 3, respectively, which stimulate the seven-center fragmentation. Though a reasonable amount of fragmentation product is obtained from 3, the through-five-bond interaction is not strong enough to dominate the reaction course completely and typical E1-like processes, i.e., elimination and rearrangement, are competitive. As expected, only a 1,2 Me-shift is observed in the reaction of the axial mesylate 4 where a gauche interaction is present in the geometry of the σ-relay. The presence of through-bond interactions in the reactions of 3 and 4 becomes apparent by comparison of the reactivity of 3 and 4 with their O-silylated analogs 5 and 6.

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Section: Resultssupporting

confidence: 80%

Chemical Consequences of Long-Range Orbital Interactions in Cholestane-3,7-diol Monosulfonate Esters. A Seven-Center Fragmentation

et al. 1996

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“…However, some of the less stable A3-isomer was formed as evidenced by the C-4 olefin resonance at 0.28 p.p.m. higher field (6) than that of the C-2 vinyl peak of 17. No still higher field n.m.r.…”

mentioning

confidence: 98%

Steroids and Steroidases. XIV. Studies on the Reactions of 2-Lithio-1,3-dithianes with Steroids Possessing Spiroepoxide Functions at C-3²

Jones¹,

Grayshan²

1972

Can. J. Chem.

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The scope of the reactions of lithio-dithianes with spiro-epoxides for various stereospecific functionalizations of alicyclic systems has been illustrated by their application to spiro-3a-and -3b-oxiranes of the Sacholestane and Sa-androstane series.La portee des reactions entre les lithio-dithianes et les epoxydes spiranniques pour fonctionnaliser de faqon stertospecifique les systimes cycliques a ete illustree par des applications sur les oxirannes-3a et 38 spiranniques dans les series Sa-cholestane et Sa-androstane.Canadian Journal of Chemistry, 50, 1407Chemistry, 50, (1972 The reactions of a 2-lithio-1,3-dithiane anion with appropriate 1,2 epoxides have been demonstrated to provide a versatile, convenient, and flexible method for the stereospecific introduction of substituents into the steroid nucleus (la, c). The facility with which such reactions occurred encouraged us to explore the scope of lithio-dithiane-epoxide reactions further and the investigations have now been successfully extended to spiro-epoxides.The ease with which spiro-epoxides would undergo reaction with dithiane anions, and establishment of the stereochemical integrity of the reactions, were evaluated on the readily available spiro-3a-and -3p-oxiranyl-5a-cholestanes 1 and 4. The synthetic sequences followed are outlined in Scheme 1.Treatment of 5a-cholestan-3-one with dimethylsulfonium methylide according to the literature procedure (2) gave a 95% yield of a mixture of 1 and 5 in the ratio 3:2. Although pure samples of 1 and 5 had not been obtained by this method in the previous work (2), it was found that separation of the two epimers could be effected by careful preparative layer chromatography (p.1.c.). The supply of the 3a-oxide 1 was augmented by its preparation in 80"/,ield from the 5a-cholestan-3-one-dimethylsulfoxonium methylide reaction (2) and in view of the more ready availability of the latter oxide, the initial experiments were carried out on the sequence of reactions involving compounds 1-4.When the 3a-epoxide 1 was kept with 2-lithio-1,3-dithiane in tetrahydrofuran at 0" for 2 days, the spiro-epoxide ring opened smoothly to give For personal use only.

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“…17 β -Hydroxy-17 α -methyl-7 β -( p -toluenesulfonyloxy)-5 α -androstan-3-one (15). A solution of 7β-hydroxysteroid 14b (88 mg, 0.27 mmol), p -toluenesulfonyl chloride (1.04 g, 5.49 mmol) in anhydrous pyridine (36 mL) was allowed to stand at 4 °C for 5 days in a sealed flask . The reaction mixture was poured into CH 2 Cl 2 (100 mL) and washed with H 2 O (50 mL).…”

Section: Methodsmentioning

confidence: 99%

“…After removal of the C-3 ketal with pTsOH/acetone, the desired 7β-alcohol 14b was isolated by flash chromatography. The 7β-tosylate 15 was prepared from 14b by reaction with pTsCl in pyridine . The halosteroids 3 and 4 were synthesized by exchange with NaI or nBu 4 NF, respectively.…”

Section: Chemistrymentioning

confidence: 99%

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7α-Iodo and 7α-Fluoro Steroids as Androgen Receptor-Mediated Imaging Agents

et al. 1999

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We have synthesized several 7alpha-fluoro (F) and 7alpha-iodo (I) analogues of 5alpha-dihydrotestosterone (5alpha-DHT) and 19-nor-5alpha-dihydrotestosterone (5alpha-NDHT) and tested them for binding to the androgen receptor and for their biological activity in an in vitro assay with cells that have been engineered to respond to androgens. The relative binding affinity to the androgen receptor determined in competition assays showed that in the androstane series the fluoro steroids have the highest affinity and that F-17alpha-CH3-DHT (4) has a higher affinity than 5alpha-DHT. All other steroids were somewhat less potent than 5alpha-DHT with F-DHT (2) = I-17alpha-CH3-DHT (3) >/= F-NDHT (6) > F-17alpha-CH3-NDHT (8) = I-DHT (1) >/= I-NDHT (5) > I-17alpha-CH3-NDHT (7). The relative biological activity in cells transfected with the androgen receptor and an androgen responsive reporter gene is 4 >> 5alpha-DHT > 2 > 6 > 3 >/= 1 >/= 8 >/= 5 > 7. The iodinated compound, I-17alpha-CH3-DHT (3), with the highest binding activity was synthesized labeled with 125I and was shown to bind with high affinity, Ka = 1.9 x 10(10) L/mol, and low nonspecific binding to the androgen receptor in rat prostatic cytosol. However, when radiolabeled [125I]-17alpha-CH3-DHT ([125I]3) was injected into castrated male rats, it showed very poor androgen receptor-mediated uptake into the rat prostate. This was unexpected in light of its superior receptor binding properties and its protection by the 17alpha-methyl group from metabolic oxidation at C-17. However, the biological potency of I-17alpha-CH3-DHT (3) was not as high as would have been expected. When I-DHT (1) and I-17alpha-CH3-DHT (3) were incubated in aqueous media at 37 degrees C they rapidly decomposed, but they were stable at 0 degrees C. The fluorinated analogue 4 treated similarly at 37 degrees C was completely stable. The products of the decomposition reaction of I-DHT (1) at 37 degrees C were identified as iodide and principally 17beta-hydroxy-5alpha-androst-7-en-3-one. The temperature dependence of this elimination reaction explains the inconsistency between the high binding to the androgen receptor (measured at 0 degrees C) and the low biological activity, as well as the poor androgen receptor mediated concentration in vivo. The fluorinated analogue F-17alpha-CH3-DHT (4) has both high affinity for the androgen receptor and high stability in aqueous media. Of the compounds tested, 4 has the highest affinity for the androgen receptor as well as the highest androgenic activity. Thus it is likely that F-17alpha-CH3-DHT 4 labeled with 18F will be an excellent receptor-mediated diagnostic imaging agent.

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Hydroxy-steroids. Part IV. The preparation and spectra of steroid olefins

Cited by 11 publications

References 0 publications

Chemical Consequences of Long-Range Orbital Interactions in Cholestane-3,7-diol Monosulfonate Esters. A Seven-Center Fragmentation

Chemical Consequences of Long-Range Orbital Interactions in Cholestane-3,7-diol Monosulfonate Esters. A Seven-Center Fragmentation

Steroids and Steroidases. XIV. Studies on the Reactions of 2-Lithio-1,3-dithianes with Steroids Possessing Spiroepoxide Functions at C-3²

7α-Iodo and 7α-Fluoro Steroids as Androgen Receptor-Mediated Imaging Agents

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Hydroxy-steroids. Part IV. The preparation and spectra of steroid olefins

Cited by 11 publications

References 0 publications

Chemical Consequences of Long-Range Orbital Interactions in Cholestane-3,7-diol Monosulfonate Esters. A Seven-Center Fragmentation

Chemical Consequences of Long-Range Orbital Interactions in Cholestane-3,7-diol Monosulfonate Esters. A Seven-Center Fragmentation

Steroids and Steroidases. XIV. Studies on the Reactions of 2-Lithio-1,3-dithianes with Steroids Possessing Spiroepoxide Functions at C-32

7α-Iodo and 7α-Fluoro Steroids as Androgen Receptor-Mediated Imaging Agents

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Steroids and Steroidases. XIV. Studies on the Reactions of 2-Lithio-1,3-dithianes with Steroids Possessing Spiroepoxide Functions at C-3²