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.     

The identification of 1,3-oxazolidine-2-thiones and 1,3-thiazolidine-2-thiones from the reaction of glucose with benzyl isothiocyanate

The structure of interaction products resulting from the reaction of unmodified glucose with benzyl isothiocyanate is reported. Prior to their identification, the main products of this reaction were isolated using solid-phase extraction (SPE) as well as preparative HPLC. They were then identified by NMR and MS as 3-benzyl-4-hydroxy-5-(D-arabino-1,2,3,4-tetrahydroxybutyl)-1,3-oxazolidine-2-thione, 3-benzyl-4-hydroxy-4-hydroxymethyl-5-(D-erythro-1,2,3-trihydroxypropyl)-1,3-oxazolidine-2-thione, N-benzyl-(D-gluco-4,5-dihydroxy-6-hydroxymethyl-tetrahydropyrano)[2,3-b]oxazolidine-2-thione and 3-benzyl-4-(N-benzyl amino)-5-(D-arabino-1,2,3,4-tetrahydroxybutyl)-1,3-thiazolidine-2-thione. The identity of the last compound was secured by X-ray crystal structure data.     

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.     

Asymmetric oxidation of racemic 2-substituted 1,3-oxathianes

Racemic 2-substituted 1,3-oxathianes were oxidized with good to high enantiomer-differentiation by using urea hydrogen peroxide addition compound as oxidant in the presence of a catalytic amount of di-mu-oxo Ti(salen) complex, giving the corresponding sulfoxides diastereoselectively.     

Microbial asymmetric oxidation of 2-butyl-1,3-propanediol

Microbial asymmetric oxidation of 2-butyl-1,3-propanediol was investigated for an efficient synthesis of S- and R-enantiomers of 2-hydroxymethylhexanoic acid (2-HMHA). From an intensive survey of the stocked bacterial strains, Acetobacter pasteurianus IAM 12073 and Pseudomonas putida IFO 3738 were found to show the highest S- and R-2-HMHA-producing activity, respectively. Under optimized conditions, A. pasteurianus (351 mg dry cell weight) and P. putida (642 mg dry cell weight) cells produced 12.0 g l⁻¹ S-2-HMHA with 89% enantiomeric excess (e.e.) at 24 h of incubation and 5.1 g l⁻¹ R-2-HMHA with 94% e.e. at 35 h of incubation from 2-butyl-1,3-propanediol.     

Antitumor evaluation and molecular docking study of substituted 2-benzylidenebutane-1,3-dione, 2-hydrazonobutane-1,3-dione and trifluoromethyl-1H-pyrazole analogues

Abstract

A series of 2-(arylidene)-1-(4-chlorophenyl)-4,4,4-trifluorobutane-1,3-diones (2–4), 4-(arylidene)-3-(4-chlorophenyl)-5-(trifluoromethyl)-4H-pyrazoles (5–7), 1-(4-chlorophenyl)-4,4,4-trifluoro-2-(2-(aryl)hydrazono)butane-1,3-diones (8, 9), 3-(4-chlorophenyl)-4-(2-(aryl)hydrazono)-5-(trifluoromethyl)-4H-pyrazoles (10, 11), 2-((3-(4-chlorophenyl)-1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)methylene)malononitrile (13), 2-((5-(4-chlorophenyl)-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)methylene)cycloalkan-1-ones (14, 15) and 1-(aryl)-3-(5-(4-chlorophenyl)-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)prop-2-en-1-ones (16, 17) were designed, synthesized and evaluated for their in vitro antitumor activity. 1-(4-Chlorophenyl)-4,4,4-trifluoro-2-(2-(4-methoxyphenyl)hydrazono)butane-1,3-dione (8) showed potential and broad spectrum antitumor activity compared to the known drug 5-FU with GI₅₀, (6.61 and 22.60 µM), TGI (42.66 and <100?µM) and LC₅₀ (93.33 and <100?µM) values, respectively. On the other hand, compound 8 yielded selective activities toward melanoma, colon, non-small lung and breast cancer cell lines compared with erlotinib and gefitinib. Molecular docking methodology was performed for compound 8 into binding site of B-RAFV600E and EGFR kinases which showed similar binding mode to vemurafenib (PLX4032) and erlotinib, respectively.     

Preparation of pseudo-arsonolipids: 2-acyloxypropane-1,3-bis(arsonic acids). The crystal structure of 2-hydroxypropane-1,3-bis(arsonic acid)

Epihalohydrins react with alkaline arsenite to give in very good yields 2-hydroxypropane-1,3-bis(arsonic acid) (7), a key compound for the synthesis of pseudo-arsonolipids and more complex arsinolipids. Through a series of reduction to -As(SPh)(2), acylation, and oxidation to -AsO(3)H(2), pseudo-arsonolipids, i.e. 2-acyloxypropane-1,3-bis(arsonic acids), were obtained. These pseudo-lipids are very sensitive to bases, being de-acylated. The bis(arsonic acid) (7) crystallizes in the orthorombic space group P2(1)2(1)2(1) with unit cell constants a=6.911(3), b=17.496(8), c=7.002(3) A. Both arsenic atoms are essentially tetrahedral being bound to three oxygens and one carbon. All hydrogen atoms have been located. There is no intramolecular but only intermolecular hydrogen bonding involving all the As=O, As-OH, and C-OH groups. The C-OH group acts as a hydrogen donor to an acidic As-OH, and this As-OH, in turn, acts as a hydrogen donor to an As=O group.     

1,3-diaryl-propanes and propan-2-ols from Virola species

The trunk woods of two Amazonian Myristicaceae, Virola minutiflora and V. elongata, contain respectively 1-(2-hydroxy-4-methoxyphenyl)-3-(3,4-m     

Stereoselective enzymatic hydrolysis of 2-cyclohexyl-and 2-phenyl-1,3-propanediol diacetate in biphasic systems

Summary A key intermediate (S(–) 2-cyclohexyl-1,3-propanediol monoacetate) was made with high optical purity for the total synthesis of a new angiotensin converting enzyme inhibitor, Fosinopril. The stereoselective hydrolysis of 2-cyclohexyl-1,3-propanediol diacetate (I) and 2-phenyl-1,3-propanediol diacetate (II) was carried out with lipases. Among various lipases evaluated, only porcine pancreatic lipase (PPL) and Chromobacterium viscosum lipase demonstrated efficient conversion and gave the desired enantiomer of monoacetate. In aqueous solution, the desired S(–) monoacetate exhibited an optical purity of 65%–80% (30%–60% enantiomeric excess [e.e.]). However, when the same reactions were conducted in a biphasic system, the product S(–) monoacetate exhibited an optical purity of 99%–100% (98%–100% e.e.). The high purity product was achieved with 65 mol% yield at 1% substrate concentration. Among various solvents evaluated in biphasic systems, efficient hydrolysis was achieved in toluene, cyclohexane, and trichloro-trifluoroethane. The crude PPL was partially purified and two lipase fractions (A and B) were identified. Lipases A and B had a molecular mass of 38 000 and 40 000 daltons, respectively, and both were found to catalyze the hydrolysis of I and II to the appropriate monoacetate in a biphasic system. Offprint requests to: R. N. Patel     

Propterol: A 1,3-diarylpropan-2-ol from Pterocarpus marsupium

The structure of propterol, an extractive of the heartwood of Pterocarpus marsupium, has been established to be 1,3-bis (4-hydroxyphenyl)propan-2-ol, on the basis of its spectral data and Jones oxidation of its dimethyl ether to known 1,3-bis(4-methoxyphenyl)propan-2-one. Propterol appears to be among the simplest of highly reduced flavonoids encountered in nature.     

Acid-catalyzed isomerization and dehydration of dl-glyceraldehyde and 1,3-dihydroxy-2-propanone

The interconversion of 2,3-dihydroxypropanal (1) and 1,3-dihydroxy-2-propanone (3) and their dehydration to pyruvaldehyde (5) has been studied in 0.5m sulfuric acid at 100°. The conversion of 1 and 3 into 5 under these conditions, in tritiated water, was monitored by isolation of 5 and determination of the distribution of carbon-bound tritium (namely, that at the aldehyde and methyl groups). This was accomplished by conversion of 5 into the phenylosazone and counting, and by conversion of 5 into pyruvic acid (isolated as the p-nitrophenylhydrazone), counting, and a difference calculation. In all cases negligible activity (about 0.8 % the activity of the solvent) was found at the aldehyde carbon of 5, derived from either 1 or 3, and parallel chromatographic studies indicated only a small extent of interconversion. As 5 incorporated tritium under conditions of its formation, plots of incorporation versus time were made and the curves extrapolated to zero time, in order to determine initial activity at the methyl group of 5, derived from either 1 or 3. This method showed that the 5 derived from 3 contained 10 % of the activity of the solvent at the methyl group as it was produced, whereas the 1-derived 5 contained no activity. In another experiment, [2-³H]1 was prepared and converted into 5. The resulting 5 was found to be labeled at C-3, indicating at C-2 → C-3 intramolecular, hydrogentransfer reaction during the conversion of 1 into 5.     

1,3-Diarylcycloalkanopyrazoles and diphenyl hydrazides as selective inhibitors of cyclooxygenase-2

Novel 1,3-diarylcycloalkanopyrazoles 1, and diphenyl hydrazides 2 were identified as selective inhibitors of cyclooxygenase-2. The 1,3-diaryl substitution pattern of the pyrazole ring in 1 differentiates these compounds from most of the known selective COX-2 inhibitors that contain two aryl rings at the adjacent positions on a heterocyclic or a phenyl ring. Similarly, the two phenyl rings in 2 are also separated by three atoms. SAR of both phenyl rings in 1 and 2, and the aliphatic ring in 1 will be discussed.     

Synthesis and antibacterial activities of chiral 1,3-oxazinan-2-one derivatives

We report here the design, synthesis, and antibacterial activities of novel classes of compounds containing chiral 1,3-oxazinan-2-ones and oxazolidinones as the basic core structures. These compounds are tertiary amines containing the core structures and two aryl substituents. Several of these molecules exhibit potent antibacterial activities against the tested Gram-positive bacteria, including Staphylococcus aureus, Enterococcus faecalis, and Bacillus subtilis. These compounds represent new structure scaffolds and can be further optimized to give new antibacterial agents with structures significantly different from those of existing classes of antibiotics.     

Synthesis and cytotoxicity studies of 1-propenyl-1,3-dihydro-benzimidazol-2-one

A heterocyclic compound 1-propenyl-1,3-dihydro-benzimidazol-2-one was synthesized by a palladium-catalyzed rearrangement reaction. Anticancer activities were confirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay against Neura 2a (neuroblastoma cell), HEK 293 (kidney cancer) and MCF-7 (breast cancer) cell lines at low micromolar range. Furthermore, clear images from phase-contrast and fluorescence microscopes and confocal images unambiguously confirm the cancer cell death. The single X-ray crystal structure of the compound unambiguously proves the structure of the benzimidazolone compound.     

Synthesis and anti-Candida activity of novel 2-hydrazino-1,3-thiazole derivatives

Eighteen new hydrazino-1,3-thiazole derivatives were evaluated against 8 strains of multi-resistant Candida spp. Introduction of an indolyl moiety linked to the hydrazone function enhanced the in vitro anti-Candida activity, with an activity spectrum towards Candida albicans strains. Introduction of a (S)-2-aminoethyl chain on the thiazole nucleus largely enhanced the in vitro antifungal activity, with a selectivity oriented towards non-C. albicans species.     

Stereocontrolled addition of enolates to chiral 2-acyl-1,3-oxathiane derivatives

Both enantiomers of 3-hydroxyalkanoates and -alkanones were prepared by the diastereocontrolled addition of enolates to ketones containing (R)-6-methyl-1,3-oxathiane moiety as a chiral auxiliary; a formation of enolate from samarium(II) iodide and alpha-bromoamide is also discussed.