Asymmetric, stereocontrolled total synthesis of paraherquamide A

The first total synthesis of paraherquamide A, a potent anthelmintic agent isolated from various Penicillium sp. with promising activity against drug-resistant intestinal parasites, is reported. Key steps in this asymmetric, stereocontrolled total synthesis include a new enantioselective synthesis of alpha-alkylated-beta-hydroxyproline derivatives to access the substituted proline nucleus and a highly diastereoselective intramolecular S(N)2' cyclization to generate the core bicyclo[2.2.2]diazaoctane ring system.     

Chemical synthesis of 15 beta-hydroxytestosterone and its derivatives using a (4-methoxyphenyl)methyl protecting group

This article describes the Community Nursing Organization, a federal health care model designed to provide specific ambulatory and outpatient services to medicare beneficiaries via a nurse managed delivery system under capitated financing. A primary nurse provider, working with the elderly client, family, physician, health care service providers, and community organizations, assesses the need for care and arranges for appropriate services. This nurse must also authorize payment of those services covered by the Community Nursing Organization (CNO). A 3-year demonstration project is currently under way. Findings at 1 year indicate that the system may have a positive effect on client health status.     

Relationship between effects on nucleic acid synthesis in cell cultures and cytotoxicity of 4-demethoxy derivatives of daunorubicin and adriamycin

Four new derivatives of daunorubicin and two new derivatives of Adriamycin characterized by the absence of the methoxyl groups at the C-4 position have been studied in cell cultures in vitro to establish structure-activity relationships. 4-Demethoxydaunorubicin was 27 to 100 times more active than was daunorubicin when inhibiting the cloning efficiency of exponential-phase HeLa cells and, like daunorubicin, was slightly active on early plateau-phase cells. DNA synthesis in mouse embryo fibroblasts stimulated by fetal calf serum was inhibited equally by the two compounds, although 4-Demethoxydaunorubicin was slightly more active than was daunorubicin when inhibiting RNA synthesis. The beta anomer of 4-demethoxydaunorubicin showed a reduced activity on HeLa cells compared to its alpha anomer, but it was equally active on DNA synthesis. The stereoisomers of 4-demethoxydaunorubicin bearing the inverted configuration in positions 7 and 9 were devoid of significant cytotoxic activity and were only slightly active on DNA synthesis at the doses tested. 4-demethoxyadriamycin and 4-demethoxy-4'-epi-adriamycin were 65 to 500 times more active than was Adriamycin on HeLa cell cloning efficiency and about 10 times more active on DNA synthesis in mouse embryo fibroblasts. Cell uptake in mouse embryo fibroblasts was also investigated for all the new derivatives tested.     

N,O-bisFmoc derivatives of N-(2-hydroxy-4-methoxybenzyl)-amino acids: useful intermediates in peptide synthesis

2-Hydroxy-4-methoxybenzyl-amino acid residues inhibit interchain association in solid phase peptide synthesis. They are easily introduced through their N,O-bisFmoc derivatives. Preparation of a range of these derivatives is described.     

4-Phenyl-4-oxo-butanoic acid derivatives inhibitors of kynurenine 3-hydroxylase

Kynurenine 3-hydroxylase (KYN 3-OHase) is a key enzyme in the kynurenine pathway of tryptophan degradation and its inhibition may be an effective mechanism for counteracting neuronal excitotoxic damage. We present here a new class of inhibitors derived from a structure-activity relationship (SAR) study of the benzoylalanine side-chain of 1. 2-hydroxy-4-(3,4-dichlorophenyl)-4-oxobutanoic acid (8) and 2-benzyl-4-(3,4-dichlorophenyl)-4-oxo-butanoic acid (10) emerged as the most interesting derivatives. Enantiospecific synthesis for both enantiomers of 8 and diastereomeric salt resolution for those of 10 were successfully applied.     

A facile enzymatic synthesis of cellooligosaccharide derivatives using beta-lactosyl fluoride

A convenient method for the preparation of cellooligosaccharide derivatives has been developed that uses beta-lactosyl fluoride as the glycosyl donor. The reaction consists of the following enzymatic processes; (1) a cellulase-catalyzed regio- and stereo-selective lactosylation of a beta-cellobioside as the glycosyl acceptor, utilizing the transglycosylating ability of an enzyme-substrate complex formed from beta-lactosyl fluoride and cellulase; (2) beta-D-galactosidase-catalyzed regioselective cleavage of the terminal D-galactose unit from the lactosylated product, giving rise to a beta-cellotrioside derivative. A cellotetraoside derivative has successfully been prepared in a stereo- and regio-selective manner by repeating these enzymatic reactions and using the resulting beta-cellotrioside as starting material.     

Anthracene-1,4,9,10-tetraone derivatives: synthesis and antitumor activity

A series of 2-alkylated anthracene-1,4,9,10-tetraone (ATO) derivatives were synthesized, and their antitumor action in ICR mice bearing S-180 cells and antiproliferative activity against L1210 cells were evaluated. Overall, the introduction of an alkyl group (C1-C8) at C-2 enhanced the antiproliferative activity. Among 2-(1-hydroxyalkyl)- or 2-(1-acetoxyalkyl)-ATO derivatives, four compounds possessing alkyl chain of an intermediate size (C4-C6) gave T/C values of > 300%. Acetylation at 1'-OH failed to cause an enhancement in the antitumor action, in contrast to a remarkable increase in antiproliferative activity. Although there was no direct relationship between antiproliferative activity and antitumor action, the compounds with lower antiproliferative activity tended to show higher antitumor activity. Further study shows that the antiproliferative activity of ATO derivatives may be explained properly neither by redox cycling nor arylating capacity.     

Naphthazarin derivatives: synthesis, cytotoxic mechanism and evaluation of antitumor activity

Patients with type Ib glycogen storage disease (GSD Ib) are susceptible to hypoglycaemic episodes. To determine whether an amylase (alpha-glucosidase) inhibitor, voglibose, can be useful in the control of hypoglycaemia, we tried it in a 14-y-old male with GSD Ib. Oral administration of voglibose prolonged the duration of normoglycaemia and reduced the incidence of hypoglycaemia attacks. These findings indicate that voglibose may be useful for preventing hypoglycaemia in GSD Ib patients.     

二安替比林甲烷芳环衍生物的合成及其在光度分析中的应用

对安替比林甲烷芳环衍生物及其显色反应进行了介绍,探讨了其结构与显色反应灵敏度的关系,并介绍了该类试剂在光度分析中的应用。     

Chemoselectively addressable HCan building blocks in peptide synthesis: L-homocanaline derivatives

OBJECTIVE: Forty-two persons were exposed to controlled low-speed rear-end automobile collisions to assess the relation between both gender and impact severity and the presence, severity, and duration of whiplash-associated disorders (WAD). Individual measures were also assessed for their potential to predict the onset of WAD. DESIGN: Experimental study subjecting individuals to a speed change of 4 km/h and 8 km/h and utilizing pretest and posttest physical examinations (immediately after and 24 hours after impact) to quantify subjects' clinical response. RESULTS: Approximately 29% and 38% of the subjects exposed to the 4 km/h and 8 km/h speed changes, respectively, experienced WAD symptoms, with cervical symptoms and headaches predominating. Objective clinical deficits consistent with WAD were measured in both men and women subjects at both 4 km/h and 8 km/h. At 4 km/h, the duration of symptoms experienced by women was significantly longer when compared with that in men (p < .05). There were no significant differences in the presence and severity of WAD between men and women at 4 km/h and 8 km/h or in the duration of WAD at 8 km/h. There was also no significant difference in the presence, severity, and duration of WAD between 4 km/h and 8 km/h. No preimpact measures were predictive of WAD. CONCLUSION: The empirical findings in this study contribute to establishing a causal relationship between rear-end collisions and clinical signs and symptoms.     

Facile and improved synthesis of 4 beta-aminopodophyllotoxin congeners

An efficient synthesis of 4 beta-aminopodophyllotoxin from 4 beta-bromopodophyllotoxin using ammonia, and also a facile synthesis of 4 beta-amino-4'-O-demethylpodophyllotoxin from 4 beta-azidopodophyllotoxin by simultaneous azido reduction and selective demethylation at 4'-position employing chlorotrimethylsilane and sodium iodide, has been described. These are potential precursors for the various 4 beta-amino analogs of podophyllotoxin possessing DNA topoisomerase II inhibition activity.     

Design and synthesis of potent antitumor 5,4'-diaminoflavone derivatives based on metabolic considerations

Recently, we reported that 5,4'-diaminoflavone (1) exhibits potent and specific growth-inhibitory activity against the estrogen receptor (ER)-positive human breast cancer cell line MCF-7. However, when compound 1 was incubated with S-9 mix, its metabolites were observed. Moreover, addition of S-9 mix to the medium caused the drastic decrease in activity of compound 1. Since the 6-, 8-, and 3'-positions were considered to be metabolized oxidatively in vivo from MO calculations, a series of 5,4'-diaminoflavone derivatives substituted at such putative metabolic positions with various functional groups were synthesized aiming at the metabolically stable derivatives. Among them, 5,4'-diamino-6,8,3'-trifluoroflavone (14d) exhibited strong growth-inhibitory activity against MCF-7 cells even in the presence of S-9 mix. Moreover, orally administered compound 14d completely suppressed the growth of MCF-7 inoculated into nude mice, and the effect was more potent than that of compound 1. In addition to ER-positive breast cancer cells, compound 14d exhibited growth-inhibitory activity against a panel of human cancer cell lines including a part of ER-negative breast, endometrial, ovarian, and liver cancers. From these results, fluorine introduction to the putative metabolic positions of compound 1 was elucidated to be effective in the enhancement of the in vivo antitumor activity, probably due to the block of the metabolic deactivation.     

MnFe2O4粉体的燃烧合成

采用燃烧合成法制备了MnFe2O4铁氧体粉体。研究了铁氧体的转化率、燃烧波速率与放热反应控制系数、氧压力之间的相互关系。通过XRD和Mossbauer谱等手段对产物的物相组成和结构进行了分析。结果表明，以燃烧合成方法制备MnFe2O4粉体的转化率较低(35％～50％)，产物存在较多的晶格缺陷，并且存在部分亚稳相，如FeMnO3。亚稳相的存在增加了粉体的烧结活性。氧压力和放热反应控制系数对MnFe2O4相的转化率影响较小。随氧压力的增加，转化率和燃烧波速率均有所增加，而且放热反应控制系数较小时，随氧压力增加的幅度更为明显。1200℃下在空气和水中对产物进行淬火，均可得到结构较完整的单相尖晶石型MnFe2O4，且阳离子趋向反型分布(反分布率α≈0．7)。     

A synthesis of 7alpha-hydroxyandrost-4-ene-3,17-dione

The first convenient chemical synthesis of 7alpha-hydroxyandrost-4-ene-3,17-dione is reported. Androsta-4,6-diene3, 17-dione was converted into its 6alpha, 7alpha-epoxy-derivative; reduction of the epoxide with aluminum amalgam gave 7alpha-hydroxyandrost-4-ene-3,17-dione. This reducing agent is more efficient than chromous acetate for the purpose.     

超/亚临界水热合成LiFePO4材料及其电化学性能

利用间歇式高温高压水热设备在超临界和亚临界条件下合成纯度高、结晶度好的亚微米级LiFePO4颗粒,通过XRD、SEM、充放电测试对LiFePO4的结构、形貌和电化学性能进行表征,并考查反应温度、压力和3种模板剂对制备的LiFePO4材料的结构、形貌及电化学性能的影响。结果表明温度和压力的升高有利于合成较小粒径、均一分布的颗粒,以PVP作为模板剂得到的样品性能最佳,制备的LiFePO4颗粒粒径为200～600 nm,0.1 C和1 C倍率下的首次放电比容量分别为141.2 mAh/g和113.6 mAh/g,1C倍率下循环100次,其容量保持率为96.0%,制备的材料具有优异的倍率性能。