- Photoinduced Molecular Transformations. Part 131. Synthesis of 18-Norsteroids, Deoxofukujusonorone and the Related Steroids, based on a Selective β-Scission of Alkoxyl Radicals as the Key Step
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A new transformation of steroids into 18-norsteroids under mild conditions is described.The key step was a regioselective β-scission of the alkoxyl radicals generated by photolysis of the hypoiodite of 18-hydroxy-18,20α-epoxy steroids, prepared by photoly
- Suginome, Hiroshi,Nakayama, Yutaka,Senboku, Hisanori
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- COMPOSITIONS AND METHODS FOR TREATING CNS DISORDERS
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Provided herein is a compound of Formula (1-I): or a pharmaceutically acceptable salt thereof, wherein R2a, R2b, R3, R4a, R4b, R5, R6a, R6b, R11a, R11b
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Paragraph 0743
(2021/01/23)
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- Facile Access to Bridged Ring Systems via Point-to-Planar Chirality Transfer: Unified Synthesis of Ten Cyclocitrinols
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Bridged ring systems are found in a wide variety of biologically active molecules including pharmaceuticals and natural products. However, the development of practical methods to access such systems with precise control of the planar chirality presents considerable challenges to synthetic chemists. In the context of our work on the synthesis of cyclocitrinols, a family of steroidal natural products, we herein report the development of a point-to-planar chirality transfer strategy for preparing bridged ring systems from readily accessible fused ring systems. Inspired by the proposed pathway for biosynthesis of cyclocitrinols from ergosterol, our strategy involves a bioinspired cascade rearrangement, which enabled the gram-scale synthesis of a common intermediate in nine steps and subsequent unified synthesis of 10 cyclocitrinols in an additional one to three steps. Our work provides experimental support for the proposed biosynthetic pathway and for the possible interrelationships between members of the cyclocitrinol family. In addition to being a convenient route to 5(10→19)abeo-steroids, our strategy also offers a generalized approach to bridged ring systems via point-to-planar chirality transfer. Mechanistic investigations suggest that the key cascade rearrangement involves a regioselective ring scission of a cyclopropylcarbinyl cation rather than a direct Wagner-Meerwein rearrangement.
- Wang, Yu,Ju, Wei,Tian, Hailong,Sun, Suyun,Li, Xinghui,Tian, Weisheng,Gui, Jinghan
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supporting information
p. 5021 - 5033
(2019/03/26)
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- Catalytic cyclometallation in steroid chemistry VI: Targeted synthesis of hybrid molecules based on steroids and tetradeca-5Z,9Z-diene-1,14-dicarboxylic acid and study of their antitumor activity
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Hybrid molecules based on a number of steroids (cholesterol, pregnenolone, androsterone) and 1,14-tetradeca-5Z,9Z-dienedicarboxylic acid linked via mono- and diethylene glycol spacers were synthesized for the first time and studied for antitumor activity in vitro. The acid was prepared using catalytic cyclomagnesiation of oxygenated 1,2-dienes with Grignard reagent in the presence of Cp2TiCl2 as the key synthetic step. Using flow cytometry, the new molecules were shown for the first time to be efficient apoptosis inducers in the HeLa, Hek293, U937, Jurkat, and K562 cell cultures and to have dose-dependent effect on the S and G2 phases of the cell cycle.
- D'yakonov, Vladimir A.,Tuktarova, Regina A.,Dzhemileva, Lilya U.,Ishmukhametova, Svetlana R.,Yunusbaeva, Milyausha M.,Dzhemilev, Usein M.
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- Scalable Synthesis of Cyclocitrinol
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A 10-step synthesis of the C25 steroid natural product cyclocitrinol from inexpensive, commercially available pregnenolone is reported. This synthesis features a biomimetic cascade rearrangement to efficiently construct the challenging bicyclo[4.4.1] A/B ring system, which enabled a gram-scale synthesis of the bicyclo[4.4.1] enone intermediate 18 in only nine steps. This work also provides experimental support for the biosynthetic origin of cyclocitrinol.
- Wang, Yu,Ju, Wei,Tian, Hailong,Tian, Weisheng,Gui, Jinghan
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supporting information
p. 9413 - 9416
(2018/07/25)
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- Non-Bioconvertible C3-Substituted Pregnenolone Derivatives for Use in the Treatment of Treatment-Resistant Depression
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The present invention relates to methods for the treatment of treatment-resistant depression (TRD), comprising the administration of compounds of formula (I), which are blocked in C3 position and cannot metabolize in vivo into pregnenolone deri
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Paragraph 0099
(2017/12/17)
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- ANTAGONISTS OF CB1 RECEPTOR.
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The invention relates to an antagonist of CB1 receptor for use in the treatment of a pathologic condition or disorder selected from the group consisting of bladder and gastrointestinal disorders; inflammatory diseases; cardiovascular diseases; nephropathies; glaucoma; spasticity; cancer; osteoporosis; metabolic disorders; obesity; addiction, dependence, abuse and relapse related disorders; psychiatric and neurological disorders; neurodegenerative disorders; autoimmune hepatitis and encephalitis; pain; reproductive disorders and skin inflammatory and fibrotic diseases.
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Page/Page column 53
(2012/12/13)
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- Use of 3-methoxy-pregnenolone in the production of a medicament for treating neurodegenerative diseases
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The invention relates to a novel use of derivatives of neurosteroids, particularly pregnenolone, for the treatment of acute or chronic lesions of the nervous system, especially certain neurodegenerative diseases, related in particular to the ability there
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Page/Page column 5
(2008/06/13)
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- Structure - Activity relationship of Aza-steroids as PI-PLC inhibitors
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A number of aza-steroids were synthesized as potent phosphatidylinositol phospholipase C (PI-PLC) inhibitors. The epimeric mixtures 22,25-diazacholesterol (8a) and 3β-hydroxy-22,25-diazacholestane (8b) were among the most active of these inhibitors, with IC50 values of 7.4 and 7.5 μM, respectively. The 20α epimer, 8a2 (IC50 = 0.64 μM), whose stereochemistry at C-20 coincides with that of cholesterol, was found 50 times more potent than the 20β epimer, 8a1 (IC50 = 32.2 μM). In diaza-estrone derivatives, the 3-methoxy group on the aromatic A-ring of 23 exhibited moderate PI-PLC inhibitory activity (IC50 = 19.7 μM), while compound with a free hydroxyl group (21) was inactive. However, in diaza-pregnane derivatives, epimers with a 3-hydroxyl group (8a, IC50 = 7.4 μM) exhibited more potent PI-PLC inhibitory activity than their counterparts with 3-methoxyl group on the non-aromatic A-ring (26, IC50 = 17.4 μM). We have illustrated in our previous publication that 3-hydroxyl-6-aza steroids are potent PI-PLC inhibitors. However, simultaneous presence of the 6-aza and 22,25-diaza moieties in one molecule as in 13, led to loss of activity. Epimeric mixture 8a showed selective growth inhibition effects in the NCI in vitro tumor cell screen with a mean GI50 value (MG-MID) of 5.75 μM for 54 tumors.
- Xie, Wenge,Peng, Hairuo,Kim, Deog-Il,Kunkel, Mark,Powis, Garth,Zalkow, Leon H.
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p. 1073 - 1083
(2007/10/03)
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- Stereoselective synthesis of a new hexanor(C23-C28) castasterone-20,22-ethyl diether from 16-dehydropregnenolone acetate and its plant growth promoting activity
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Stereoselective synthesis of a new hexanor(C23-C28)castasterone-20,22-ethyl diether 22 has been achieved in sixteen steps from cheap and readily available 16-dehydropregnenolone acetate. This new brassinosteroid has shown typical brassin activity in mung bean epicotyl bioassay.
- Hazra, Braja G.,Basu, Sourav,Bahule, Bharat B.,Pore, Vandana S.,Vyas, Brahmanand N.,Ramraj, Velaswamy M.
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p. 4909 - 4920
(2007/10/03)
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