Steroids. LXXVII.<sup>1</sup> Synthesis and Reactions of 16β-Oxygenated Pregnan-20-one Derivatives

Löken, Bjarte; Kaufmann, St.; Rosenkranz, G.; Sondheimer, Franz

doi:10.1021/ja01589a071

Cited by 30 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The hydroxylation of steroids is an important enzymatic reaction in steroid metabolism and the resultant hydroxylated steroids can be used as the key-intermediates for the biosynthesis of steroid drugs with diverse therapeutic purposes [1,2,3,4,5]. Both chemical and biological approaches are thus used for the production of hydroxylated steroids [4,5,6,7,8]. Chemical synthesis suffers from the complexity of hydroxysteroids, as well as the necessity of extreme reaction conditions and the production of toxic by-products [9,10].…”

Section: Introductionmentioning

confidence: 99%

Probing Steroidal Substrate Specificity of Cytochrome P450 BM3 Variants

Liu

Wang

et al. 2016

Molecules

View full text Add to dashboard Cite

M01A82W, M11A82W and M01A82WS72I are three cytochrome P450 BM3 (CYP102A1) variants. They can catalyze the hydroxylation of testosterone (TES) and norethisterone at different positions, thereby making them promising biocatalysts for steroid hydroxylation. With the aim of obtaining more hydroxylated steroid precursors it is necessary to probe the steroidal substrate diversity of these BM3 variants. Here, three purified BM3 variants were first incubated with eight steroids, including testosterone (TES), methyltestosterone (MT), cholesterol, β-sitosterol, dehydroepiandrosterone (DHEA), diosgenin, pregnenolone and ergosterol. The results indicated that the two 3-keto-∆ 4 -steroids TES and MT can be hydroxylated at various positions by the three BM3 mutants, respectively. On the contrary, the three enzymes displayed no any activity toward the remaining six 3-hydroxy-∆ 5 -steroids. This result indicates that the BM3 mutants prefer 3-keto-∆ 4 -steroids as hydroxylation substrates. To further verify this notion, five other substrates, including two 3-hydroxy-∆ 5 -steroids and three 3-keto-∆ 4 -steroids, were carefully selected to incubate with the three BM3 variants. The results indicated the three 3-keto-∆ 4 -steroids can be metabolized to form hydroxysteroids by the three BM3 variants. On the other hand, the two 3-hydroxy-∆ 5 -steroids cannot be hydroxylated at any position by the BM3 mutants. These results further support the above conclusion, therefore demonstrating the 3-keto-∆ 4 -steroid substrate preference of BM3 mutants, and laying a foundation for microbial production of more hydroxylated steroid intermediates using BM3 variants.

show abstract

Section: Introductionmentioning

confidence: 99%

Probing Steroidal Substrate Specificity of Cytochrome P450 BM3 Variants

Liu

Wang

et al. 2016

Molecules

View full text Add to dashboard Cite

show abstract

“…Presumably, attack of the chloride ion at C7 is hindered by the geminal dimethyl group, thus preventing the nucleophile from achieving the required trajectory to open the epoxide ring at the β-position. The formation of an α-halo species is unusual with only a few examples in the literature . Analysis of the 1 H NMR 3 J couplings between H7 and H8 in 20 (∼12 Hz) suggested that H7 and H8 were pseudo-trans-diaxially orientated in 20 , thus implying that the chlorine and hydroxyl groups were in a pseudo-trans-diequatorial orientation.…”

Section: Resultsmentioning

confidence: 99%

Total Synthesis of (±)-Hyphodermins A and D

et al. 2008

View full text Add to dashboard Cite

An efficient formal synthesis of (+/-)-hyphodermins A and D, metabolites of Hyphoderma radula, has been completed in 12 and 11 steps, respectively. The tricyclic carbon skeleton of enone 6 was rapidly assembled from diester 11 via an alpha brominationn-elimination sequence followed by anhydride formation. Regioselective reduction of the lactone group of enone 6 with LiAlH(t-BuO) 3 gave lactol 15. Lactol 15 was converted in two steps to (+/-)-hyphodermin D, without the need for complex protection-deprotection strategies. Lactol 15 was converted in three steps to (+/-)-hyphodermin A, via the key step of epoxidation of an enone in the presence of a THP lactol. A combination of NMR and ab initio studies suggests that the structures of hyphodermin C and D should be interchanged.

show abstract

“…The 3p, 16a, 17P, 18-tetra01 (34) in 2,2-dimethoxypropane 34 and dimethylformamide containing a catalytic HO amount of toluene-p-sulphonic acid at 80 "C was found to form an acetonide (36) between the 17P-and 18-hydroxy groups because the bridging of 16a and 17p would require excessive strain. Acetylation of the derivative (36) gave the 3P,16adiacetate(37), confirmed from the 'H n.m.r. spectrum which showed that the 16p-and 3a-proton signals had each moved downfield by nearly 1 p.p.m.…”

mentioning

confidence: 83%

“…230-233 "C, v, , , . 17$,18-IsopropyZidenedioxyandrost-5-ene-3~, 16a-diol (26) and Its Diacetate (37).-The 3P,16a,17P,18-tetraol (34) (1 1.3 mg, 0.035 mmol) was treated with 2,2-dimethoxypropane (0.36 ml) in dimethylformamide (0.06 ml) containing toluene-p-sulphonic acid (0.4 mg) under reflux for 3 h. The solvents were removed under reduced pressure and the residue was extracted with ethyl acetate; the extract was washed with aqueous sodium hydrogen carbonate and water until neutral, dried (Na2C03), and evaporated under reduced pressure to give the acetonide (36) (7.3…”

Section: P16al8-triucetoxypregn-5-ene-17~20f3-diolmentioning

confidence: 99%

18-Substituted steroids. Part 11. Synthesis of 3β,16α,18-trihydroxyandrost-5-en-17-one, a neonatal urinary metabolite, and the 3,16,18-triacetate of its 16β-epimer

Das¹,

Kirk²

1984

J. Chem. Soc., Perkin Trans. 1

View full text Add to dashboard Cite

3~,16a,l8-Trihydroxyandrost-5-en-17-one and the triacetate of its 16P-epimer have been synthesized from 3phydroxypregna-5,16-dien-ZO-one via the 'hypoiodite' reaction of the derived 3P-acetoxy-1 6a,l7a-epoxypregn-5-en-2O-ols to functionalize C-18, followed by controlled opening of the epoxide ring by reagents chosen to give either 3p,16a,18-or 3p,1 6~,18-triacetoxy-l7a-hydroxypregn-5en-20-one. Reduction of the 20-0x0 group and oxidative cleavage of the C(17)-C(20) bond produced the corresponding 3~,16,18-triacetoxyandrost-5-en-17-one. 3P,16a,18-Trihydroxyandrost-5-en-17one was obtained by deacetylation of its triacetate, but the 16P-epimer rearranged on hydrolysis to give 3~,17~,18-trihydroxyandrost-5-en-16-0ne. The androst-5-ene-3~,16,17p,18-tetraols were also prepared.

show abstract

Steroids. LXXVII.¹ Synthesis and Reactions of 16β-Oxygenated Pregnan-20-one Derivatives

Cited by 30 publications

References 0 publications

Probing Steroidal Substrate Specificity of Cytochrome P450 BM3 Variants

Probing Steroidal Substrate Specificity of Cytochrome P450 BM3 Variants

Total Synthesis of (±)-Hyphodermins A and D

18-Substituted steroids. Part 11. Synthesis of 3β,16α,18-trihydroxyandrost-5-en-17-one, a neonatal urinary metabolite, and the 3,16,18-triacetate of its 16β-epimer

Contact Info

Product

Resources

About

Steroids. LXXVII.1 Synthesis and Reactions of 16β-Oxygenated Pregnan-20-one Derivatives

Cited by 30 publications

References 0 publications

Probing Steroidal Substrate Specificity of Cytochrome P450 BM3 Variants

Probing Steroidal Substrate Specificity of Cytochrome P450 BM3 Variants

Total Synthesis of (±)-Hyphodermins A and D

18-Substituted steroids. Part 11. Synthesis of 3β,16α,18-trihydroxyandrost-5-en-17-one, a neonatal urinary metabolite, and the 3,16,18-triacetate of its 16β-epimer

Contact Info

Product

Resources

About

Steroids. LXXVII.¹ Synthesis and Reactions of 16β-Oxygenated Pregnan-20-one Derivatives