14504-94-0Relevant articles and documents
Optimization of the 11α-hydroxylation of steroid DHEA by solvent-adapted Beauveria bassiana
Gonzalez, Richard,Nicolau, Felipe,Peeples, Tonya L.
, p. 103 - 109 (2017)
To extend the use of Beauveria bassiana for commercial applications, the optimization of reaction conditions and accurate prediction of biotransformation products are necessary. This work enhances the selective hydroxylation capacity of strain ATCC 7159, resulting in a cost effective and eco-friendly process for the synthesis of valuable 11α-hydroxy steroids. Our work establishes the biochemical pathway of DHEA to hydroxylated intermediates with strain ATCC 7159, and distinguishes the optimum conditions for reactor arrangements, substrate concentration, reaction temperature, and pH. Higher substrate conversion, selectivity, and yield of desired product was achieved with “resting cells.” Addition of higher volumes of growing medium relative to reaction buffer increases the reaction rate. When a diluted amount of substrate is used, a higher yield of 11α-hydroxy steroids is achieved. Also, reactions at 26 °C with pH ranges between 6.0 and 7.0 result in the highest conversion (70%) and the higher product yield (45.8%). B. bassiana has the capacity to metabolize DHEA and similar steroids in different reaction schemes, and has a promising future as biocatalyst to be used in the production of drug metabolites.
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.
