139973-51-6Relevant articles and documents
Imprinted polymers as protecting groups for regioselective modification of polyfunctional substrates
Alexander, Cameron,Smith, Craig R.,Whitcombe, Michael J.,Vulfson, Evgeny N.
, p. 6640 - 6651 (1999)
Imprinted polymers were prepared using a functional monomer derived from boronophthalide and a number of steroid templates bearing spatially separated hydroxyl groups. The cooperative nature of the binding interaction was demonstrated in polymers imprinted with androst-5-ene-3β,17β-diol and its structural analogues. The stoichiometry and kinetics of binding were probed using IR spectroscopy, selective solvent extractions, and chemical modification experiments. The feasibility of using imprinted polymers as reusable protecting groups was established by the regioselective acylation of trihydroxysteroids bound to polymers imprinted with structurally related diols. In polymers prepared with tert-butyl ester templates "matched" to the substrate, regioselectivities as high as 23.1:1 (24-acetate:3-acetate) in the monoester products (65% of recovered material) were seen. In the "unmatched" case, the ratio fell to 5.4:1; however, in functionally identical control polymers, imprinted with ethylene glycol, the regioselectivity was completely reversed (1:100), and only poor yields of monoesters (13%) were obtained.
Gut,Uskokovic
, p. 673,675 (1959)
-
Kuwada,Joyama
, (1938)
-
Regio- and stereoselective reduction of 17-oxosteroids to 17β-hydroxysteroids by a yeast strain Zygowilliopsis sp. WY7905
Liu, Yuanyuan,Wang, Yu,Chen, Xi,Wu, Qiaqing,Wang, Min,Zhu, Dunming,Ma, Yanhe
, p. 17 - 24 (2017)
The reduction of 17-oxosteroids to 17β-hydroxysteroids is one of the important transformations for the preparation of many steroidal drugs and intermediates. The strain Zygowilliopsis sp. WY7905 was found to catalyze the reduction of C-17 carbonyl group of androst-4-ene-3,17-dione (AD) to give testosterone (TS) as the sole product by the constitutive 17β-hydroxysteroid dehydrogenase (17β-HSD). The optimal conditions for the reduction were pH 8.0 and 30 °C with supplementing 10 g/l glucose and 1% Tween 80 (w/v). Under the optimized transformation conditions, 0.75 g/l AD was reduced to a single product TS with >90% yield and >99% diastereomeric excess (de) within 24 h. This strain also reduced other 17-oxosteroids such as estrone, 3β-hydroxyandrost-5-en-17-one and norandrostenedione, to give the corresponding 17β-hydroxysteroids, while the C-3 and C-20 carbonyl groups were intact. The absence of by-products in this microbial 17β-reduction would facilitate the product purification. As such, the strain might serve as a useful biocatalyst for this important transformation.
Photoinduced Molecular Transformations. Part 132. A Two-Step Intramolecular Transposition of the 17β-Acetyl Group of Pregnan-20-one to C-18 through the Formation of Cyclobutanols by the Reaction of the Excited Carbonyl, followed by a Selective β-Scission of Alkoxyl Radicals generated..
Suginome, Hiroshi,Nakayama, Yutaka
, p. 1843 - 1848 (1992)
New two-step transformations of a pregnan-20-one into 18-functionalized androstanes and 18a,18b-dihomoandrostanes are described; a type-II reaction of an excited pregnan-20-one protected in the A,B-ring gave the corresponding 20-hydroxy-18,20-cyclopregnane.Selective β-scission of the cyclobutanoxylradicals generated by irradiation of the nitrite or the hypoiodite gave a 5:4 ratio of the corresponding 18a,18b-dihomo-5α-androstane-18a-one and 18-iodoandrostan-17β-yl acetate in 89percent yield or 18a,18b-dihomo-5α-androstane-17,18a-dione 17-oxime in 83percent yield.The transformation involves a novel two-step intramolecular transposition of the 17β-acetyl group to C-18, and an oxygen insertion to the C-17-C-20 bond of pregnan-20 one.Several chemoselective transformations of the functional groups of the 18-iodoandrostan-17-one and 18a,18b-dihomo-5α-pregnan-18a-one, including the synthesis of 3β-hydroxy-18a,18b-dihomoandrost-5-ene-17,18a-dione, are reported.
C-6α- vs C-7α-Substituted Steroidal Aromatase Inhibitors: Which Is Better? Synthesis, Biochemical Evaluation, Docking Studies, and Structure-Activity Relationships
Roleira, Fernanda M. F.,Varela, Carla,Amaral, Cristina,Costa, Saul C.,Correia-Da-Silva, Georgina,Moraca, Federica,Costa, Giosuè,Alcaro, Stefano,Teixeira, Natércia A. A.,Tavares Da Silva, Elisiário J.
, p. 3636 - 3657 (2019/04/26)
C-6α and C-7α androstanes were studied to disclose which position among them is more convenient to functionalize to reach superior aromatase inhibition. In the first series, the study of C-6 versus C-7 methyl derivatives led to the very active compound 9 with IC50 of 0.06 μM and Ki = 0.025 μM (competitive inhibition). In the second series, the study of C-6 versus C-7 allyl derivatives led to the best aromatase inhibitor 13 of this work with IC50 of 0.055 μM and Ki = 0.0225 μM (irreversible inhibition). Beyond these findings, it was concluded that position C-6α is better to functionalize than C-7α, except when there is a C-4 substituent simultaneously. In addition, the methyl group was the best substituent, followed by the allyl group and next by the hydroxyl group. To rationalize the structure-activity relationship of the best inhibitor 13, molecular modeling studies were carried out.
Multiple Enone-Directed Reactivity Modes Lead to the Selective Photochemical Fluorination of Polycyclic Terpenoid Derivatives
Pitts, Cody Ross,Bume, Desta Doro,Harry, Stefan Andrew,Siegler, Maxime A.,Lectka, Thomas
supporting information, p. 2208 - 2211 (2017/02/23)
In the realm of aliphatic fluorination, the problem of reactivity has been very successfully addressed in recent years. In contrast, the associated problem of selectivity, that is, directing fluorination to specific sites in complex molecules, remains a great, fundamental challenge. In this report, we show that the enone functional group, upon photoexcitation, provides a solution. Based solely on orientation of the oxygen atom, site-selective photochemical fluorination is achieved on steroids and bioactive polycycles with up to 65 different sp3 C-H bonds. We have also found that γ-, β-, homoallylic, and allylic fluorination are all possible and predictable through the theoretical modes reported herein. Lastly, we present a preliminary mechanistic hypothesis characterized by intramolecular hydrogen atom transfer, radical fluorination, and ultimate restoration of the enone. In all, these results provide a leap forward in the design of selective fluorination of complex substrates that should be relevant to drug discovery, where fluorine plays a prominent role.
