利用路易斯酸介导的2,3-环氧吡喃糖硫苷的重排反应立体选择性合成2-脱氧吡喃糖苷(英文)

本研究描述了利用2,3-环氧吡喃糖硫苷作为糖基化试剂制备2-脱氧吡喃糖苷的方法。在Cu(OTf)_2的介导下,2,3-环氧吡喃糖硫苷与糖基受体发生重排并进行糖基化反应生成2-硫代-2-脱氧糖苷。该方法立体选择性高,可能会在制备具有重要生物活性的2-脱氧糖苷方面有广泛的应用。     

N,N-二异丙基乙二胺的合成

目的合成得到N,N-二异丙基乙二胺,以降低生产成本。方法以二异丙胺和丙烯酰胺为起始原料,经Michael加成和Hofmann降解两步反应合成得到目标化合物。结果目标化合物总收率为55.3%,经核磁共振氢谱确证结构正确。结论该方法操作简单,原料廉价易得,适合工业化生产。     

1,2-二硫戊环类天然产物及其衍生物的研究进展

1,2-二硫戊环(1,2-dithiolane)类天然产物是一类特殊的五元杂环类化合物。由于五元环的张力比较大,使其具有良好的反应活性;又因为硫环容易开环成巯基,使其具有较强的抗氧化能力,可以清除过多的氧自由基,维持体内自由基的平衡。因此,1,2-二硫戊环类天然产物得到了生物医学界越来越多的关注。本文综述了四类含有1,2-二硫戊环结构的天然产物,包括海洋天然产物二硫吡咯酮抗生素(dithiolopyrrolone antibiotic）、kottamide E以及硫辛酸（lipoic acid）和芦笋酸（asparagusic acid）,综述了它们的研究历程、生物活性或应用以及主要的合成方法。     

6‐Substituted Indolo[1,2‐c]quinazolines as New Antimicrobial Agents

A series of 2‐o‐arylidineaminophenylindoles and their cyclic derivatives (indolo[1,2‐c]quinazolines) were synthesized. The reactions occurred under relatively mild conditions and afforded the desired product in good yields. Molecular structures of the synthesized compounds were confirmed by IR, ¹H‐NMR, ¹³C‐NMR, MS spectra, and elemental analyses. Furthermore, all the final products were screened for in‐vitro antibacterial activity against three Gram‐positive and three Gram‐negative bacteria and also tested for their inhibitory action against three strains of fungi. Compound IIc showed potent activity against all the bacterial (except S. typhimurium) and fungal strains. Especially, compounds IIi and IIj which have isoquinolyl and pyridyl substituents displayed potent antibacterial as well as antifungal activities compared to those of the respective standard drugs Ampicillin and Ketoconazole.     

log P Estimation of 1,2-Dithiole-3-thiones and 1,2-Dithiole-3-ones: A Comparison of Experimental and Calculative Approaches

Purpose To estimate experimental log P values of formerly described 5-formyl- and 5-acyl-dithiole-3-thiones (DTT) and -dithiole-3-ones (DTO) and to check the validity of five log P calculation programs via experimental log P for a database of 68 DTT and DTO.Methods Experimental log P values were measured by means of octanol/water partitioning; for determining solute concentrations in water, RP-HPLC with spectrophotometric detection was used. For calculating log P, the fragmental methods ACD/log P, CLOGP, and KOWWIN, the atom-based approach XLOGP, and the whole-molecule approach QLOGP were applied.Results Quality of calculations significantly differs depending on the subset under consideration. For database compounds 01–48, comprising alkyl and aryl substitution in 4- and 5-position, the fragmental methods ACD/log P, CLOGP, and KOWWIN perform significantly better than the atom-based approach XLOGP and the whole-molecule method QLOGP. For database compounds 49–68, comprising formyl and acyl substitution in 4- and 5-position, superiority of the whole-molecule method QLOGP over the substructure-based approaches is observed. The strong underestimation of log P for compounds 49–68 probably indicates hidden physicochemical phenomena resulting from the juxtaposition of the acyl and dithiole moieties.Conclusions All calculation methods included in this study need a thorough refinement to adequately cope with particular solvation behavior suspected to prevail in formyl- or acyl-DTT and DTO, which represent a chemical class of high pharmacological interest.     

Acute nephrotoxicities and hepatotoxicities of 1,2-dibromo-3-chloropropane and 1,2-dibromoethane in male and female F344 rats

Four consecutive intraperitoneal (i.p.) injections with 40 mg/kg of 1,2-dibromo-3-chloropropane (DBCP) reduced the in vitro accumulation of p-aminohippurate (PAH) and tetraethylammonium (TEA) by slices of renal cortex and increased blood urea nitrogen (BUN) concentration in both male and female rats, but elevated serum glutamic pyruvic transaminase (GPT) and glutamic oxaloacetic transaminase (GOT) activities in females only. Four consecutive treatments with 1,2-dibromoethane (EDB) reduced the accumulation of PAH in male rats, but failed to alter TEA accumulation, BUN concentration or GPT and GOT activities in rats of either sex. Single i.p. injections of EDB or DBCP (40 mg/kg, approximately one-half of the acute, i.p. LD50 values) were without effect on serum GPT and GOT activities, BUN concentration or the accumulations of PAH and TEA in male rats when measured 24, 48 or 96 h after treatment, except that PAH accumulation was reduced at 96 h.These results indicate that BUN and the accumulations in vitro of PAH and TEA by renal cortical slices are appropriate endpoints for studying DBCP nephrotoxicity. Measurements of serum GOT and GPT activities detected DBCP hepatotoxicity in female rats only. The nephrotoxicity of EDB was indicated by measurement of TEA accumulation only.     

Synthesis and Antiproliferative Activitiy of Novel Diaryl Ureas Possessing a 4H‐Pyrido[1,2‐a]pyrimidin‐4‐one Group

We herein disclose a series of novel diaryl urea derivatives possessing a 4H‐pyrido[1,2‐a]pyrimidin‐4‐one group as novel potent anticancer compounds. The structures were confirmed by IR, ¹H‐NMR, and MS. All the compounds were screened for their antiprofilerative activity agaist the human breast cancer cell line (MDA‐MB‐231). The pharmacological results indicated that most of the compounds showed moderate activity. The best of this series is compound 4c (IC₅₀ = 0.7 μmol/L), with a potency 3.6‐fold higher than Sorafenib (IC₅₀ = 2.5 μmol/L), which was approved in 2005.     

Respiratory pathology in rats and mice after inhalation of 1,2-dibromo-3-chloropropane or 1,2 dibromoethane for 13 weeks

Seventy F344 rats and 144 B6C3F1 mice were subdivided into seven groups. Three groups were each exposed via inhalation to 1, 5, or 25 ppm of 1,2-dibromo-3-chloropropane (DBCP) for 6 h per day, 5 days per week for 13 weeks. Three additional groups were each similarly exposed to 3, 15, or 75 ppm of 1,2-Dibromoethane (EDB). The remaining group was exposed to room air under the same conditions. At 13 weeks, rats and mice showed severe necrosis and atrophy of the olfactory epithelium in the nasal cavity after inhalation of 5 or 25 ppm DBCP and 75 ppm EDB. Lower concentrations induced squamous cell metaplasia, hyperplasia and cytomegaly of the epithelium of the respiratory nasal turbinals. Squamous metaplasia, hyperplasia and cytomegaly of the epithelium was also seen in larynx, trachea, bronchi and bronchioles. Other compound related toxic lesions in rats were seen in the liver, kidney and testes.     

Sex- and age-related nephrotoxicity due to 1,2-dichloropropane in vitro

Sex- and age-related nephrotoxicity due to 1,2-dichloropropane was studied in vitro by means of renal cortical slices obtained from Wistar rats. Reduced glutathione content, organic anion accumulation (p-aminohippurate), and release of malondialdehyde (to measure the extent of lipid peroxidation), aspartate aminotransferase, -glutamyltransferase and lactate dehydrogenase into the incubation medium were determined. Sex differences in naive rats parameters were slight, but male were more susceptible to toxic effects of 1,2-dichloropropane than female rats; glutathione depletion, lipid peroxidation, and loss of organic anion accumulation were higher in male than in female slices. During senescence, naive male rats showed a progressive decrease of glutathione content (statistically significant from 7–9 months of age), increase of spontaneous lipid peroxidation from the same age, and increase of signs of cytotoxicity (release of aspartate aminotransferase and lactate dehydrogenase into the incubation medium) from 3–4 months of age. A loss of organic anion accumulation started from 7–9 months of age. Slices from rats of 3–4 months old showed the apparently highest susceptibility to 1,2-dichloropropane but depletion of glutathione content and loss of organic anion accumulation were at the same level in the oldest rats. The age decrease of control values caused the differences in the percentage ratio and then, apparently, a lower DCP effect. On the contrary, the increase of aspartate aminotransferase released in the incubation medium by DCP-treated slices corresponded to the age-related increase in cytotoxicity.The work was presented in part to the 1st National Conference of the Molecular and Cellular Toxicology Group, Siena 30. 11.–1.12.1990.     

2,2-双取代-4,6-二氨基-1,2-二氢-1-羟基-s-三嗪类化合物的合成研究

目的 对三嗪类化合物进行合成研究。方法 以盐酸羟胺和苯甲酰氯为原料，经酰化、烃化、水解、缩合、环合及脱苄反应合成目的物。结果和结论 共合成了9个2，2-双取代-4，6-二氨基-l，2-二氢-l-羟基-s-三嗪类化合物(11-i)，结构经元素分析、红外吸收光谱、核磁共振氢谱及质谱确证。     

咪唑并[1,2-b]哒嗪的制备

咪唑并[1，2-b]哒嗪（1）是合成头孢菌素类抗生素头孢唑兰（cefozopran）的中间体，文献用6-氯咪唑并[1，2-b]哒嗪（4）经Pd／C催化氢解制得1，但4在国内市场尚无商品供应。本研究参考相关文献，用价廉易得的3，6-二氯哒嗪（2）经氨解制得3-氨基-6-氯哒嗪（3），与氯乙醛缩合制得4，再经Pd／C催化氢解制得1（图1），并进行了工艺改进。