Steroids LXXVI. Stereospecific formation of α- and β-epoxides in the reaction of dimethylsulfonium methylide and dimethylsulfoxonium methylide with dihydrotestosterone

Cook, Clarence; Corley, Robert C.; Wall, Monroe E.

doi:10.1016/s0040-4039(01)99494-8

Cited by 16 publications

(5 citation statements)

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“…3 mp ) 194-195°for natural material). This substance was identical to natural fumagillin in all respects (TLC, 1 H NMR, 13 C NMR). The synthetic material had [R] D ) -27.0°(lit.…”

mentioning

confidence: 65%

“…At this point, debenzoylation allowed us to compare our synthetic (-)-fumagillol 23 with authentic material prepared from natural fumagillin. The two were indentical by TLC, 1 H NMR, and 13 C NMR. The synthetic material had [R] D ) -68.8°(lit.…”

mentioning

confidence: 97%

“…This transformation could proceed by inversion of the quaternary center. While this might be possible, we elected instead to cleave the diol to the ketone, then establish the epoxide using the equatorial-selective sulfoxonium ylide. We had been concerned that the intermediate β,γ-unsaturated ketone, from periodate cleavage of diol 19 , would be unstable.…”

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confidence: 99%

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Synthesis of (−)-Fumagillin

et al. 1999

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“…3 mp ) 194-195°for natural material). This substance was identical to natural fumagillin in all respects (TLC, 1 H NMR, 13 C NMR). The synthetic material had [R] D ) -27.0°(lit.…”

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confidence: 65%

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confidence: 97%

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Synthesis of (−)-Fumagillin

et al. 1999

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“…The reaction was carried out at room temperature for 12 h. Under these conditions, the stereoisomer (20 R )- 2 was obtained as the main product. The selectivity of this reaction is believed to be due to the high reactivity of the dimethylsulfonium methylide. , This sulfur ylide is unstable and may readily attack the less hindered α-side of 20-ketone to form the (20 R )-epoxide. The configuration of the 20-epoxide was confirmed by the two oxirane proton signals in its 1 H-NMR spectrum (ppm: 2.33 doublet and 2.50 doublet), which agrees with the reported data for the 3-acetate of 2 …”

Section: Resultsmentioning

confidence: 99%

“…The procedure of Counsell et al 24 was followed to prepare N-methyl-17β-formamidoandrost-5-en-3β-ol (18) from dehydroepiandrosterone (17) and N-methylformamide under reductive amination in formic acid. Oppenauer oxidation of 18 provided N-methyl-17β-formamidoandrost-4-en-3-one (19).…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Evaluation of Pregnane Derivatives as Inhibitors of Human Testicular 17α-Hydroxylase/C_17,20-Lyase^,

Son

et al. 1996

J. Med. Chem.

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The pregnene derivatives with modifications at the 17,20-side chain and D-ring were synthesized and evaluated as inhibitors of human testicular 17 alpha-hydroxylase/C17,20-lyase. The results demonstrate that compounds which have 20-substituents with moderate to strong dipole properties, such as 20-oxime (3, 20), 20 beta-ol (24, 30), and 20 beta-carboxaldehyde (27), are potent inhibitors of this enzyme complex. The 20-substituents with hydrophobic property were devoid of inhibitory activity, e.g., the dimethylhydrazones 8 and 9. The 16-ene together with 20-oxime (20) showed the most potent inhibition of this enzyme complex, whereas 17(20)-ene modification as in 17(20)-ene-20-carbonitrile (14) did not increase activity in comparison to the 20 beta-carbonitrile (16). The bioisotere of 27 with 20-aza (19) also reduced the inhibitory activity. The results showed that isomeric configurations at the 20-position of some steroidal compounds are important factors which influence the potency of the inhibition significantly (e.g., 20 beta-ols 24 and 30 were 3-5-fold more potent than 20 alpha-ols 23 and 29). As expected, some compounds based on the pregn-5-en-3 beta-ol skeleton, which is similar to the natural substrate of human testicular 17 alpha-hydroxylase/C17,20-lyase in A- and B-rings, showed more potent inhibition than similar compounds which are based on the pregn-4-en-3-one skeleton (e.g., 23-25 compared to 29-31). These results suggest that A- and B-rings make significant contributions to the binding of these steroidal compounds to the 17 alpha-hydroxylase and C17,20-lyase. In comparison to ketoconazole, a nonsteroidal inhibitor of 17 alpha-hydroxylase and C17,20-lyase which has been used in the treatment of prostatic cancer, the steroidal compounds 20, 24, and 27 demonstrate more potent inhibition for this enzyme complex. These inhibitors warrant further investigation in biological systems. The structural features of these compounds may serve as leads in the design of new inhibitors.

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Reactions of cyclic ethers

Gritter

1967

PATAI'S Chemistry of Functional Groups

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Steroids LXXVI. Stereospecific formation of α- and β-epoxides in the reaction of dimethylsulfonium methylide and dimethylsulfoxonium methylide with dihydrotestosterone

Cited by 16 publications

References 3 publications

Synthesis of (−)-Fumagillin

Synthesis of (−)-Fumagillin

Synthesis and Evaluation of Pregnane Derivatives as Inhibitors of Human Testicular 17α-Hydroxylase/C_17,20-Lyase^,

Reactions of cyclic ethers

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Steroids LXXVI. Stereospecific formation of α- and β-epoxides in the reaction of dimethylsulfonium methylide and dimethylsulfoxonium methylide with dihydrotestosterone

Cited by 16 publications

References 3 publications

Synthesis of (−)-Fumagillin

Synthesis of (−)-Fumagillin

Synthesis and Evaluation of Pregnane Derivatives as Inhibitors of Human Testicular 17α-Hydroxylase/C17,20-Lyase,

Reactions of cyclic ethers

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Synthesis and Evaluation of Pregnane Derivatives as Inhibitors of Human Testicular 17α-Hydroxylase/C_17,20-Lyase^,