- Phytosterols as precursors for the synthesis of aromatase inhibitors: Hemisynthesis of testololactone and testolactone
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Using β-sitosterol and stigmasterol as precursor materials, a concise and efficient hemisynthesis of aromatase inhibitors: testololactone and testolactone was accomplished in a well-established reaction scheme. It involves highly effective Oppaneur oxidation of both β-sitosterol as well as stigmasterol to generate the required enone moiety in ring 'A' of the desired steroid system. The Oppaneur oxidation products of both β-sitosterol and stigmasterol were then subjected to oxidative cleavage of the side chain to produce 4-androstene-3,17-dione. Baeyer-Villiger oxidation of 4-androstene-3,17-dione using m-CPBA yielded testololactone. Dehydrogenation of 4-androstene-3,17-dione using phenylselenyl chloride in ethyl acetate followed by selenoxide elimination with H2O2 in dichloromethane furnished androstenedienone. Baeyer-Villiger oxidation of the resulting androstenedienone yielded the desired testolactone (overall yield 33%). This expeditious reaction scheme may be exploited for the bulk production of aromatase inhibitors (especially testolactone marketed under the brand name Teslac) from the most abundant and naturally occurring phytosterols like β-sitosterol.
- Lone, Shabir H.,Bhat, Khursheed A.
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p. 164 - 168
(2015/03/04)
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- Synthesis and evaluation of some steroidal oximes as cytotoxic agents: Structure/activity studies (I)
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The side chain of a compound plays an important role in its biological function. In our studies, we have found that hydroximinosteroid derivatives with different side chains and position of hydroximino on ring A and B displayed remarkable distinct cytotoxicities against a diversity of cancer cell types. Presence of an oxime group on ring B and a hydroxy on ring A or B resulted in a higher cytotoxicity than other structural motifs. In addition, a cholesterol-type side chain at position 17 was required for the biological activity. Our findings provide new evidence showing the relationship between the chemical structure and biological function. The information obtained from the studies may be useful for the design of novel chemotherapeutic drugs.
- Cui, Jian-Guo,Fan, Lei,Huang, Li-Liang,Liu, Hong-Li,Zhou, Ai-Min
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experimental part
p. 62 - 72
(2009/04/10)
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- Chromatographic separation of putative precursors of cholestanol
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This paper describes convenient syntheses for labeled and unlabeled cholest-5-en-3-one, cholest-4-en-3-one, epicholesterol, cholest-4-en-3β-ol, and cholest-4-en-3α-ol. The thin-layer chromatography, high-performance liquid chromatography, and gas-liquid chromatography of these compounds and of cholestanol and epicholestanol are also described. The synthesized compounds are potential precursors in the biosynthesis of cholestanol in mammals.
- Batta,Salen,Shefer
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p. 109 - 122
(2007/10/02)
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- Plasma lipoproteins as drug carriers: Pharmacological activity and disposition of the complex of β-sitosteryl-β-D-glucopyranoside with plasma lipoproteins
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The ability of plasma lipoproteins to act as carriers in site-specific drug delivery systems was evaluated by determining the disposition and pharmacological effects of β-sitosteryl-β-D-glucopyranoside (SG, 3). In the disposition studies, [3H]SG was absorbed from the intestinal tract by the formation of chylomicrons and was specifically associated with lipoproteins in vivo. [3H]SG was incorporated into various rat plasma lipoproteins in vitro. [3H]SG complexed with the lower density lipoproteins (d 3H]SG complexed with the higher density lipoproteins (d ≥ 1.063 g/mL) following intravenous administration to rats. In pharmacological studies, the hemostatic effect of SG in mice and the inhibitory effect of SG on vascular permeability in rats were only observed after intravenous administration of the complexes of SG with the lower density lipoproteins. The same results were obtained after the intravenous administration of the complexes of SG with human and mouse lipoproteins.
- Seki,Okita,Watanabe,Nakagawa,Honda,Tatewaki,Sugiyama
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p. 1259 - 1264
(2007/10/02)
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