25680-68-6Relevant academic research and scientific papers
Selective synthesis of the two main progesterone metabolites, 3α-hydroxy-5α-pregnanolone (allopregnanolone) and 3α-hydroxypregn-4-en-20-one, and an assessment of their effect on proliferation of hormone-dependent human breast cancer cells
Kuznetsov, Y. V.,Levina, I. S.,Mikhaevich, E. I.,Scherbakov, A. M.,Tserfas, M. O.,Zavarzin, I. V.
, p. 552 - 557 (2020/04/21)
A directed synthesis of two progesterone metabolites, allopregnanolone and 3a-hydroxy-pregn-4-en-20-one, from Δ16-pregnanolone and progesterone, respectively, was carried out by a reduction of the carbonyl groups in positions 3 and subsequent inversion of the configuration of the resulting alcohols by the Mitsunobu reaction. The selectivity of the reduction of the conjugated carbonyl group in position 3 of progesterone with sodium borohydride in the presence of cerium(III) chloride (Luche reduction) was demonstrated. The ef ect of the obtained metabolites on the proliferation of breast cancer cells of the MCF-7 and T47D lines under normal and steroid-free conditions was studied. It is shown that the ef ect of these compounds on the proliferation depends on the presence of additional steroids in the culture medium. Metabolites exerted small cytostatic ef ects on the growth of the MCF-7 cells under standard conditions, while the transfer of the cells to a steroid-free medium weakened these cytotoxic ef ects. In the experiments with the T47D line cells, the cell growth was stimulated under both standard and steroid-free conditions. Allopregnanolone and progesterone stimulate the growth to a greater extent under steroid-free conditions than under standard ones.
A Practical and Stereoselective In Situ NHC-Cobalt Catalytic System for Hydrogenation of Ketones and Aldehydes
Zhong, Rui,Wei, Zeyuan,Zhang, Wei,Liu, Shun,Liu, Qiang
supporting information, p. 1552 - 1566 (2019/06/14)
Homogeneous catalytic hydrogenation of carbonyl groups is a synthetically useful and widely applied organic transformation. Sustainable chemistry goals require replacing conventional noble transition metal catalysts for hydrogenation by earth-abundant base metals. Herein, we report how a practical in situ catalytic system generated by easily available pincer NHC precursors, CoCl2, and a base enabled efficient and high-yielding hydrogenation of a broad range of ketones and aldehydes (over 50 examples and a maximum turnover number [TON] of 2,610). This is the first example of NHC-Co-catalyzed hydrogenation of C=O bonds using flexible pincer NHC ligands consisting of a N-H substructure. Diastereodivergent hydrogenation of substituted cyclohexanone derivatives was also realized by fine-tuning of the steric bulk of pincer NHC ligands. Additionally, a bis(NHCs)-Co complex was successfully isolated and fully characterized, and it exhibits excellent catalytic activity that equals that of the in-situ-formed catalytic system. Catalytic hydrogenation is a powerful tool for the reduction of organic compounds in both fine and bulk chemical industries. To improve sustainability, more ecofriendly, inexpensive, and earth-abundant base metals should be employed to replace the precious metals that currently dominate the development of hydrogenation catalysts. However, the majority of the base-metal catalysts that have been reported involve expensive, complex, and often air- and moisture-sensitive phosphine ligands, impeding their widespread application. From a mixture of the stable CoCl2, imidazole salts, and a base, our newly developed catalytic system that formed easily in situ enables efficient and stereoselective hydrogenation of C=O bonds. We anticipate that this easily accessible catalytic system will create opportunities for the design of practical base-metal hydrogenation catalysts. A practical in situ catalytic system generated by a mixture of easily available pincer NHC precursors, CoCl2, and a base enabled highly efficient hydrogenation of a broad range of ketones and aldehydes (over 50 examples and up to a turnover number [TON] of 2,610). Diastereodivergent hydrogenation of substituted cyclohexanone derivatives was also realized in high selectivities. Moreover, the preparation of a well-defined bis(NHCs)-Co complex via this pincer NHC ligand consisting of a N-H substructure was successful, and it exhibits equally excellent catalytic activity for the hydrogenation of C=O bonds.
STEROID ANALOGUES FOR NEUROPROTECTION
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Page/Page column 103-104, (2009/10/21)
Provided are steroid analogues functionalized with polar substituents at the C3 and/or C20 positions of the steroid ring system that exhibit improved water solubility. Also provided are pharmaceutical compositions comprising the steroid analogues and methods using the novel steroid analogues for the treatment and prevention of neurodegeneration in a patient following injury to the central nervous system.
Synthesis of the allylic gonadal steroids, 3α-hydroxy-4-pregnen-20-one and 3α-hydroxy-4-androsten-17-one, and of 3α-hydroxy-5α-pregnan-20-one
Wiebe,Deline,Buckingham
, p. 39 - 51 (2007/10/02)
A method for the convenient synthesis of the recently isolated allylic gonadal steroids, 3α-hydroxy-4-pregnen-20-one (3α-dihydroprogesterone; 3α-DHP) and 3α-hydroxy-4-androsten-17-one (3α-HA), was developed using 4-pregnene-3,20-dione (progesterone) and 4-androstene-3,17-dione as substrates and potassium trisiamylborohydride (KS-Selectride) as reducing agent. Similar reactions were also used for the reduction of 5α-pregnane-3,20-dione to 3α-hydroxy-5α-pregnan-20-one (3α-HP). The yields were about 15%, 50%, and >90% for 3α-DHP, 3α-HA and 3α-HP, respectively. Structures of the products, including the 3β-isomers and the 17α-epimer, formed in these reactions were determined by NMR and mass spectroscopic methods.
Preparation of a Polymer-supported Diol and Its Use in isolating Aldehydes and Ketones from Mixtures and as a Protecting Group for Aldehydes and Ketones
Hodge, Philip,Waterhouse, Janette
, p. 2319 - 2323 (2007/10/02)
Reaction of cross-linked chloromethylated polystyrenes with 3-mercaptopropane-1,2-diol and sodium hydroxide under phase-transfer conditions gave polymers containing diol residues.A range of aldehydes and ketones were successfully bound to these polymers via acetal formation.The aldehydes and ketones were released by treating the products with aqueous dioxane in the presence of toluene-p-sulphonic acid.The polymer-supported diol could be used to isolate aldehydes or ketones from mixtures with other compounds and to separate a 3-oxosteroid from a 17- or a 20- oxosteroid.The supported diol was successfully used to protect the aldehyde group of undec-10-enal whilst the terminal vinyl group was transformed into -CH2CH2OCOPh.Attempts to monoprotect dicarbonyl compounds were unsuccessful.
SELECTIVITE DE LA REDUCTION DE L'ANDROSTEN-4 DIONE-3,17 ET DE LA PROGESTERONE PAR DIVERS BOROHYDRURES: ROLE DE L'ASSISTANCE ELECTROPHILE PAR LE CATION OU UN SOLVANT HYDROXYLE
D'Incan, E.,Loupy, A.,Restelli, A.,Seyden-Penne, J.,Viout, P.
, p. 1755 - 1760 (2007/10/02)
The reduction of Δ4-androsten-3,17 dione 1 and of progesterone 2 by nBu4NBH4 is highly chemisoselective: in THF only the α-enone moiety is reduced, the saturated C17 or C20 keto group being kept unchanged.When TMEDA is added, saturated alcohols are obtained, without any allylic alcohol when the reaction goes to completion.However this reduction is poorly stereoselective as 70:30 mixtures of A/B cis and trans ring junction compounds are obtained.In MeOH, the saturated keto group is more than 90percent selectively reduced.However, the reduction of 1 and 2 by LiBH4 and Zn(BH4)2 is poorly chemioselective.These results are interpreted in terms of competition between electrophilic assistance and steric effects.
METAL-ASSISTED REACTIONS-12. UNUSUAL SELECTIVITY IN THE REDUCTION OF KETONES WITH ZINC OR CADMIUM BIS-TETRAHYDROBORATE/DIMETHYLFORMAMIDE COMPLEX
Hussey, Brendan J.,Johnstone, Robert A. W.,Boehm, Peter,Entwistle, Ian D.
, p. 3769 - 3774 (2007/10/02)
Zinc bis-tetrahydroborate forms a solid complex with dimethylformamide (DMF) of composition, Zn(BH4)2*1.5DMF.Unlike zinc bis-tetrahydroborate itself, the complex with DMF can be stored as a solid at room temperature.Ketones and aldehydes are reduced to the corresponding alcohols by the complex but the mechanism of reduction appears to be different from that using zinc bis-tetrahydroborate itself and from other tetrahydroborates in that only one hydride equivalent from each BH4- unit is utilized and not four.Further, although saturated aliphatic ketones are reduced rapidly to alcohols, aromatic ketones react much more slowly and α,β-unsaturated ketones react very slowly so that the complex appears to have selective reducing potential with regard to different classes of ketones.It is also apparent that the zinc bis-tetrahydroborate/DMF complex reduces sterically hindered saturated ketones much more slowly than it does unhindered ketones.An analogous cadmium bis-tetrahydroborate/DMF complex can be prepared in solution and reacts with ketones similarly to the zinc complex.
