Formation of oligonuclear complexes between copper(II) and 1-hydroxyethane-1,1-diphosphonic acid

The complex formation between Cu(II) and 1-hydroxyethane-1,1-diphosphonic acid was studied by means of pH-potentiometry and spectroscopy (UV-Vis and EPR). Speciation revealed the formation of a trinuclear complex [Cu₃A₃]⁶⁻ besides the mononuclear 1:1 and 1:2 species. In the complex [Cu₃A₃]⁶⁻ , which is not formed with other diphosphonic derivatives, the ligands adopt chelating and bridging modes via the four O atoms of the two phosphonates, the alcoholic-OH groups remaining in the protonated form.     

Synthesis of 1,3-Dithiane-2-thiones

A number of new 1, 3-dithiane-2-thione derivatives were synthesized from bismesylates of substituted 1, 3-dihydroxypropanes by the reaction with sodium trithiocarbonate provided from Na₂S and CS₂. The cyclic structures were elucidated on the basis of the IR, UV, NMR, and mass spectra, together with elemental analyses and chemical reactions.     

Inhibition of glycerol-3-phosphate acyltransferase by analogs of glycerol-3-phosphate.

Analogs of glycerol-3-phosphate were tested as substrates or inhibitors of the glycerol-3-phosphate acyltransferases of mitochondria and microsomes. (rac)-3,4-Dihydroxybutyl-1-phosphonate, (rac)-glyceraldehyde 3-phosphate, (rac)-3-hydroxy-4-oxobutyl-1-phosphonate, (1S,3S)-1,3,4-trihydroxybutyl-1-phosphonate, and (1R,3S)-1,3,4 trihydroxybutyl-1-phosphonate were competitive inhibitors of both mitochondrial and microsomal sn-glycerol-3-phosphate acyltransferase activity. An isosteric analog of dihydroxyacetone phosphate, 4-hydroxy-3-oxobutyl-1-phosphonate, was a much stronger competitive inhibitor of the microsomal than the mitochondrial enzyme. Phenethyl alcohol was a noncompetitive inhibitor of both the microsomal and the mitochondrial acyltransferases. The product of the mitochondrial acyltransferase reaction with (rac)-3,4-dihydroxybutyl-1- phosphonate was almost exclusively (rac)-4-palmitoyloxy-3-hydroxybutyl-1-phosphonate. The microsomal acylation reaction generated both the monoacyl product and (S)-3,4-dipalmitoyloxybutyl-1-phosphonate. The apparent Km for (S)-3,4-dihydroxybutyl-1-phosphonate was 2.50 and 1.38 mM for the mitochondrial and microsomal enzymes, respectively.     

Synthesis of glycerol 1,3-dihexadecyl ether

The synthesis of 1,3-dihexadecyloxy-2-propanol (glycerol 1,3-dihexadecyl ether) is reported. The method is applicable to the preparation of other 1,3-disubstituted glycerols where the substituents are not affected by acid or by catalytic hydrogenolysis conditions.     

Relationship between glycerol-3-phosphate dehydrogenase,fatty acid synthase and fatty acid binding proteins in developing human placenta

The activities of the enzymes glycerol-3-phosphate dehydrogenase and fatty acid synthase are inhibited by palmitoyl-coenzyme A and oleate. The two isoforms of fatty acid binding proteins (PI 6.9 and PI 5.4) enhance the activities of glycerol-3-phosphate dehydrogenase and fatty acid synthase in the absence of palmitoyl-coenzyme A or oleate and also protect them against palmitoyl-coenzyme A or oleate inhibition. Levels of fatty acid binding proteins, the activities of the enzymes fatty acid synthase and glycerol-3-phosphate dehydrogenase increase with gestation showing a peak at term. However, the activity of fatty acid synthase showed the same trend up to the 30th week of gestation and then declined slightly at term. With the advancement of pregnancy when more lipids are required for the developing placenta, fatty acid binding proteins supply more fatty acids and glycerol-3-phosphate for the synthesis of lipids. Thus a correlation exists between glycerol-3-phosphate dehydrogenase, fatty acid synthase and fatty acid binding proteins in developing human placenta.     

2-芳基-1,3-二氧环戊烷的合成与表征

以3-硝基-4-甲基苯甲酸为主要原料,依次通过乙硼烷还原、氯代反应将其中羧基转化为氯甲基,又经过缩争、氧化、醛基保护将甲基转化为缩醛等步骤合成了2-[2-硝基-(4-氯甲基)]苯基-1,3-二氧环戊烷.目标产物及某些重要中间体的结构已通过红外光谱、质谱、核磁共振氢谱的方法进行了表征.     

Synthesis and antiviral activities of N-9-oxypurine 1,3-dioxolane and 1,3-oxathiolane nucleosides

Two series of 1,3-dioxolanes and 1,3-oxathiolane nucleosides containing N-9-oxypurine were synthesized as potential antiviral agents. These compounds were prepared by reacting the sugar moieties with iodo- or bromotrimethylsilane, followed by treatment with a mixture of sodium hydride and the desired N-hydroxy purine base. The preparation of these N-hydroxybases was also described. No significant antiviral activity was observed against HIV, HBV, HSV-1, HSV-2, or HCMV.     

Selective inhibition of Trypanosoma brucei GAPDH by 1,3-bisphospho-D-glyceric acid (1,3-diPG) analogues

Various phosphono-phosphates and diphosphonates were synthesized as 1,3-diphosphoglycerate (1,3-diPG) analogues by using a beta-ketophosphonate, an alpha-fluoro,beta-ketophosphonate or a beta-ketophosphoramidate to mimic the unstable carboxyphosphate part of the natural substrate. The inhibitory effect of these analogues on glyceraldehyde-3-phosphate dehydrogenases (GAPDH) from Trypanosoma brucei (Tb) and rabbit muscle were measured with respect to both substrates, glyceraldehyde-3-phosphate (GAP) and 1,3-diPG. Interestingly, all 1,5-diphosphono,2-oxopentanes without substitution at the C-3 position selectively inhibit the Tb GAPDH with respect to 1,3-diPG and are without effect on Rm GAPDH. All 1-phospho,3-oxo,4-phosphonobutanes show themselves to be non-selective inhibitors either with regard to substrates or organisms, but they will be of a great interest as 1,3-diPG stable models for structural studies of co-crystals with GAPDHs.     

Synthesis and metabolism of glycerol-3H triether, a nonabsorbable oil-phase marker for lipid absorption studies

A saturated mixed-chain glycerol triether, 1-hexadecyl-2,3-didodecyl glycerol (1-hexadecoxy-2,3-didodecoxypropane), was synthesized with (3)H at positions 9 and 10 or (14)C at position 1 of the hexadecyl moiety. In acute feeding experiments in rats, less than 0.2% of the triether was absorbed, based on lymph and fecal recoveries. Radioactivity was present exclusively as triether in feces, indicating that it was not degraded by digestive or bacterial enzymes. Chronic feeding experiments in rats confirmed the nonabsorbability of the triether and further indicated that it was nontoxic, did not influence the absorption of dietary fat, and mixed intimately with the fat present in colonic contents and feces. The triether that was absorbed was deposited as triether in adipose tissue, liver, and spleen. When administered intraperitoneally to mice, the triether was stored in the tissues and was not metabolized. When the triether was partitioned between an oil phase of triolein or fatty acid and monoglyceride, and an aqueous micellar phase, the triether remained exclusively in the oil phase. The triether appears to be an ideal nonabsorbable oil-phase marker for use in lipid absorption studies.     

Accelerated decarboxylation of 1,3-dimethylorotic acid in ionic liquid

The solvent effect of ionic liquids on the decarboxylation of 1,3-dimethylorotic acid and its analogue in ionic was investigated. The rate acceleration observed was proposed to be a result of the stabilization of the zwitterionic intermediates by the charged groups available in these special solvents.     

Roots of nutrient-deprived Brachiaria species accumulate 1,3-di-O-trans-feruloylquinic acid

A novel di-hydroxycinnamoylquinic acid ester, 1,3-di-O-trans-feruloylquinic acid (DFQA), was isolated from roots of nutrient-deprived Brachiaria species--the most widely sown tropical forage grasses in South America. In contrast to other so far characterized quinic-acid esters, DFQA exists in a chair conformation with the carboxylic group in the axial orientation. It accumulates in older parts of the root system, but not in root apices or shoots. Higher levels were found in B. ruziziensis, which is poorly adapted to infertile acid soils, than in well adapted B. decumbens. DFQA was also found in the soil, most likely as a result of root decay, because it was not detected in root exudates of plants cultivated in solution culture. Nitrogen and phosphorus deficiency--but not aluminum toxicity or deprivation of other nutrients--stimulated its synthesis in roots. Its accumulation was correlated with a shift in biomass partitioning toward the root system.     

Synthesis and analysis of potential α1,3-fucosyltransferase inhibitors

Fucosyltransferases catalyze the transfer of l-fucose from an activated GDP-β-l-fucose to various acceptor molecules such as N-acetyllactosamine. Frequently fucosylation is the final step within the glycosylation machinery, and the resulting glycans are involved in various cellular processes such as cell–cell recognition, adhesion and inflammation or tumor metastasis. The selective blocking of these interactions would thus be a potential promising therapeutic strategy. The syntheses and analyses of various potential α1,3-fucosyltransferase inhibitors derived from GDP-β-l-fucose containing a triazole linker unit is summarized and the observed inhibitory effect was compared with that of small molecules such as GDP or fucose. To examine their specificity and selectivity, all inhibitors were tested with human α1,3-fucosyltransferase IX and Helicobacter pylori α1,3-fucosyltransferase, which is to date the only α1,3-fucosyltransferase with a known high resolution structure. Specific inhibitors which inhibit either H. pylori α1,3-fucosyltransferase or human fucosyltransferase IX with K_i values in the micromolar range were identified. In that regard, acetylated GDP-galactose derivative Ac-3 turned out to inhibit H. pylori α1,3-fucosyltransferase but not human fucosyltransferase IX, whereas GDP-6-amino-β-l-fucose 17 showed an appreciably better inhibitory effect on fucosyltransferase IX activity than on that of H. pylori fucosyltransferase.     

Synthesis and antitumor-evaluation of 1,3-selenazole-containing 1,3,4-thiadiazole derivatives

A series of novel 1,3-selenazole-containing 1,3,4-thiadiazole derivatives bearing Schiff base moieties were synthesized and evaluated for their in vitro antiproliferative activities against human breast cancer cell MCF-7 and mouse lymphocyte leukemia cell L1210 by CCK-8 assay. The majority of the compounds showed better activity against MCF-7 cell, compared with lead compound PCS. In particular, compound 6c was the most potent compound with IC₅₀ value of 4.02 μM.     

Asymmetric Synthesis of Optically Active 1,3-Oxathiolane Nucleoside Analogues

Abstract

A ready asymmetric synthesis of 3′-oxa-4′-thionucleosides has been accomplished in three main steps from benzoyloxyethanal. The synthesis is characterized by high overall yield and appreciable enantiomeric excesses. It represents a general synthetic scheme to prepare a wide range of heterosubstituted sulfur-containing nucleoside analogues.     

Synthesis of highly unsaturated phosphatidylcholines in the development of sperm motility: a role for epididymal glycerol-3-phosphorylcholine

Summary Interpretation of the experimental literature on epididymal glycerophosphorylcholine metabolism according to a recently proposed de novo pathway for the synthesis of acyl-specific phosphatidylcholine suggests that epididymal glycerophosphorylcholine is an intermediate of this proposed pathway. This glycerophosphodiester is postulated to be utilized by spermatozoa to synthesize docosahexaenoic phosphatidylcholine, proposed to be required for the development of sperm motility. A defect in glycerophosphorylcholine synthesis might be responsible for some forms of asthenozoospermia.