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The chemical synthesis and biological oxidation of 7-alpha-hydroxy[26-14C]cholesterol, 7-dehydro[26-14C]cholesterol and 26-hydroxy[26-14C]cholesterol.

ABSTRACT: 1. 26-Hydroxycholesterol was obtained by reducing the methyl ester of (+/-)-3beta-hydroxycholest-5-en-26-oic acid, which was synthesized from 25-oxonorcholesterol. 2. Methods for preparing 7alpha-hydroxycholesterol and 7-dehydrocholesterol were modified to allow the micro-scale preparation of these [(14)C]sterols from [26-(14)C]-cholesterol. 3. 26-Hydroxycholesterol was oxidized more readily than 7alpha-hydroxycholesterol, 7-dehydrocholesterol or cholesterol by mitochondrial preparations from livers of mice, rats, guinea pigs, common toads (Bufo vulgaris) and Caiman crocodylus. 4. (+/-)-3beta-Hydroxy[26-(14)C]cholest-5-en-26-oic acid was oxidized very rapidly to (14)CO(2) by mouse and guinea-pig mitochondria without evident discrimination between the two optical isomers. 5. An enzyme system that oxidizes 26-hydroxycholesterol to 3beta-hydroxycholest-5-en-26-oic acid was identified in the soluble extract of rat-liver mitochondria. This enzyme could use NADP in place of NAD but was not identical with liver alcohol dehydrogenase (EC 1.1.1.1). 6. [26-(14)C]Cholesteryl 3beta-sulphate was not oxidized by fortified mouse-liver preparations that oxidized [26-(14)C]cholesterol to (14)CO(2).

SUBMITTER: Dean PD

PROVIDER: S-EPMC1264860 | biostudies-other | 1966 Feb

REPOSITORIES: biostudies-other

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Chemical synthesis and biological evaluation of ω-hydroxy polyunsaturated fatty acids.

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| S-EPMC5584617 | biostudies-literature

Cholesterol metabolism. Effect of 26-thiacholesterol and 26-aminocholesterol, analogues of 26-hydroxycholesterol, on cholesterol synthesis and low-density-lipoprotein-receptor binding.

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| S-EPMC1135347 | biostudies-other

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Asymmetric Chemoenzymatic One-Pot Synthesis of α-Hydroxy Half-Esters.

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Semi-Synthesis and Biological Evaluation of 25(R)-26-Acetoxy-3β,5α-Dihydroxycholest-6-One.

Project description:Previously, we identified a series of steroids (1-6) that showed potent anti-virus activities against respiratory syncytial virus (RSV), with IC50 values ranging from 3.23 to 0.19 µM. In this work, we first semi-synthesized and characterized the single isomer of 5, 25(R)-26-acetoxy-3β,5α-dihydroxycholest-6-one, named as (25R)-5, in seven steps from a commercially available compound diosgenin (7), with a total yield of 2.8%. Unfortunately, compound (25R)-5 and the intermediates only showed slight inhibitions against RSV replication at the concentration of 10 µM, but they possessed potent cytotoxicity activities against human bladder cancer 5637 (HTB-9) and hepatic cancer HepG2, with IC50 values ranging from 3.0 to 15.5 µM without any impression of normal liver cell proliferation at 20 µM. Among them, the target compound (25R)-5 possessed cytotoxicity activities against 5637 (HTB-9) and HepG2 with IC50 values of 4.8 µM and 15.5 µM, respectively. Further studies indicated that compound (25R)-5 inhibited cancer cell proliferation through inducing early and late-stage apoptosis. Collectively, we have semi-synthesized, characterized and biologically evaluated the 25R-isomer of compound 5; the biological results suggested that compound (25R)-5 could be a good lead for further anti-cancer studies, especially for anti-human liver cancer.

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Molybdenum imidazole citrate and bipyridine homocitrate in different oxidation states - balance between coordinated α-hydroxy and α-alkoxy groups.

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Sustainable Triazine-Based Dehydro-Condensation Agents for Amide Synthesis.

Project description:Conventional methods employed today for the synthesis of amides often lack of economic and environmental sustainability. Triazine-derived quaternary ammonium salts, e.g., 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM(Cl)), emerged as promising dehydro-condensation agents for amide synthesis, although suffering of limited stability and high costs. In the present work, a simple protocol for the synthesis of amides mediated by 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) and a tert-amine has been described and data are compared to DMTMM(Cl) and other CDMT-derived quaternary ammonium salts (DMT-Ams(X), X: Cl- or ClO4-). Different tert-amines (Ams) were tested for the synthesis of various DMT-Ams(Cl), but only DMTMM(Cl) could be isolated and employed for dehydro-condensation reactions, while all CDMT/tert-amine systems tested were efficient as dehydro-condensation agents. Interestingly, in best reaction conditions, CDMT and 1,4-dimethylpiperazine gave N-phenethyl benzamide in 93% yield in 15 min, with up to half the amount of tert-amine consumption. The efficiency of CDMT/tert-amine was further compared to more stable triazine quaternary ammonium salts having a perchlorate counter anion (DMT-Ams(ClO4)). Overall CDMT/tert-amine systems appear to be a viable and more economical alternative to most dehydro-condensation agents employed today.

| S-EPMC7795458 | biostudies-literature

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