Total synthesis of cyclodepsipeptide Hikiamides A-C / 中国药科大学学报

@#Total synthesis of cyclodepsipeptide Hikiamides A-C was described. Fragment convergent condensation method was applied for the preparation of Hikiamides A-C, starting from Commercially available amino acid such as L-N-Boc-Phe-OH, L-N-Boc-Trp-OH, L-N-Cbz-Van-OH etc. Tripeptide fragments(compounds 5a/5b)and dipeptide fragments(compounds 8a/8b)were first prepared. The subsequent condensation of the resulted two fragments provided protected linear pentapetides(compounds 9a/9b/9c); Finally, the linear pentapetide was cyclized by a mixed condensing agents comprised of PyBOP and HBTU. Hikiamides A-C was obtained with total yields of 9%, 11% and 6. 5%, respectively. Compared with the natural source, this method has the advantages of low cost, convenient operation and high yield, which effectively solves the problem of low isolated yield of Hikiamides A-C from Fusarium sp.

Association between metabolic syndrome with QTc interval prolongation in physical examination subjects / 重庆医学

Objective To explore the relationship between metabolic syndrome(MS) and corrected QT(QTc) interval prolongation.Methods A total of 1 260 participants having electrocardiogram examinations,aged over 18 years old from June 2015 to June 2016 were included and divided into the MS group and non-MS group.QTc was calculated according to the Bazett formula.The Logistic regression model was established for exploring the association between MS and QTc.Results There were 63 cases of QTc interval prolongation in the MS group,however,40 cases in the non-MS group(P＜0.01).In the unadjusted model,MS was a risk factor of QTc interval prolongation[OR =6.36,95 ％ CI(2.34,8.67),P＜ 0.01].After further adjusting confounders,MS was still correlated with QTc interval prolongation[OR =4.11,95 ％ CI(2.09,7.13,P＜ 0.01].In the study of the relationship between the MS groups with QTc interval prolongation,after adjusting confoundingfactors,only abdominal obesity[OR=2.76,95％ CI(1.43,7.56),P＜0.01] and hypertriglyceridemia[OR=1.75,95％CI(1.22,4.31),P=0.013)] were closely correlated with QTc interval prolongation.Conclusion MS is an independent risk factor of QTc interval prolongation.It is especially important to strengthen the management of blood lipid and abdominal circumference.

Total synthesis of sauropunol A-D isolated from Sauropus rostratus genus plants / 中国药科大学学报

Sauropunol A-D potentially with anti-inflammatory,anti-bacterial activities were recently isolated from traditional Chinese medicinal plant Sauropus rostratus.Herein,we report the total synthesis of sauropunol (A-D) starting from a commercially available 2-deoxy-D-arabino-hexopyranose.The trifluoromethane sulfonation of intermediates could simultaneously trigger intramolecular cyclization to afford 3,6-anhydro hexofuranoside scaffold.The following deprotection reaction could produce sauropunol A,B and C/D with total yields of 21％,5％,and 17％ (isomer sauropunol C/D),respectively.Structures of the target compounds were confirmed by comparison with NMR spectroscopic properties of those previously reported.

Diagnostic value of head-up tilt test in patients with cough syncope / 重庆医学

Objective To investigate the diagnostic value of head-up tilt test (HUT) in cough syncope (CS).Methods Forty-seven outpatients or inpatients with CS and 79 patients with suspected vasovagal syncope(SVVS) due to syncope history in our hospital from January 2011 to May 2015 served as the observation group and control group respectively.HUT was performed in the two groups.The cough response during HUT,changes of systolic pressure and diastolic pressure caused by cough,HUT positive results and hemodynamic type were observed,Results In the observation group,4 cases(8.51％) were cough caused syncope,26 cases (55.32 ％) were presyncope and 17 cases (36.17 ％) had no symptoms,while 79 cases in the control group had no symptoms,the differences were statistically significant (P＜ 0.05).The total positive rate of cough response in the observation group was 63.83％,and the specificity was 100.00％.The systolic blood pressure had statistical difference between the two groups(.P＜0.05).The diastolic pressure had statistical difference between the cases of non-symptoms with the cases of syncope and cases of presyncope in the observation group (P＜0.05),but had no statistical difference compared with the cases of non-symptoms in the control group(P＞0.05).The heart rate(HR) had no statistical difference among various groups(P＞0.05).The HUT positive rate in the observation group was lower than that in the control group(P＜0.05).The hemodynamic type had no statistical difference between the two groups(P＞0.05).Conclusion Severe coughing during HUT may cause the blood pressure decrease,induces syncope or presyncope,can increase the diagnostic sensitivity of CS patients,which is very useful in the suspected diagnosis of CS patients,especially for CS patients with a unclear history.

Diagnostic value of head-up tilt test in patients with cough syncope / 重庆医学

Objective To investigate the diagnostic value of head-up tilt test (HUT) in cough syncope (CS).Methods Forty-seven outpatients or inpatients with CS and 79 patients with suspected vasovagal syncope(SVVS) due to syncope history in our hospital from January 2011 to May 2015 served as the observation group and control group respectively.HUT was performed in the two groups.The cough response during HUT,changes of systolic pressure and diastolic pressure caused by cough,HUT positive results and hemodynamic type were observed,Results In the observation group,4 cases(8.51％) were cough caused syncope,26 cases (55.32 ％) were presyncope and 17 cases (36.17 ％) had no symptoms,while 79 cases in the control group had no symptoms,the differences were statistically significant (P＜ 0.05).The total positive rate of cough response in the observation group was 63.83％,and the specificity was 100.00％.The systolic blood pressure had statistical difference between the two groups(.P＜0.05).The diastolic pressure had statistical difference between the cases of non-symptoms with the cases of syncope and cases of presyncope in the observation group (P＜0.05),but had no statistical difference compared with the cases of non-symptoms in the control group(P＞0.05).The heart rate(HR) had no statistical difference among various groups(P＞0.05).The HUT positive rate in the observation group was lower than that in the control group(P＜0.05).The hemodynamic type had no statistical difference between the two groups(P＞0.05).Conclusion Severe coughing during HUT may cause the blood pressure decrease,induces syncope or presyncope,can increase the diagnostic sensitivity of CS patients,which is very useful in the suspected diagnosis of CS patients,especially for CS patients with a unclear history.

Synthesis and antiplatelet aggregation/antioxidant activity of 3-alkyl-benzo c selenophen-1 3 H -ones / 中国药科大学学报

Phthaloyl dichloride (1)was reacted with LiAlSeH2 to give benzo[c]selenophene-1;3-dione (2);which was treated with the Grignard reagents to generate hydroxyl compounds 3a-3h.These compounds were finally converted to target products 4a-4h by treatment with hydriodic acid.The structures of 4a-4h were confirmed by MS and 1 H NMR.Their inhibitory activity against adenosine diphosphate (ADP)-induced platelet aggregation was evaluated by Born′s turbidimetric assay;free radical scavenging activity was assayed by xanthine oxidasemethod and 1;10-phenanthroline spectrophotometric method.It was found that compound 4 f displayed more potent inhibi-tory effect on platelet aggregation than 3-n-butylphthalide and comparable hydroxyl free radical scavenging activity in vitro to that of edaravone.Therefore;compound 4 f might be the candidate for further investigation.

The correlation between wide QRS of transesophageal atrial pacing and implicit ventricular pre-excitation / 中国基层医药

Objective To explore the correlation between wide QRS of transesophageal atrial pacing (TEAP) and implicit ventricular pre-excitation.Methods 77 patients tested by TEAP were divided into two groups according to the ECG results .45 patients in group Ⅰhad normal electrocardiogram .32 patients in group Ⅱhad ven-tricular pre-excitation.In group Ⅰ,TEAP results showed that electric pulse wave (S wave) was followed by intermit-tent or continuous wide QRS complex .At the same time , the results of group Ⅰ were compared with the results of groupⅡ.Results (1)The patients of group Ⅰwere excluded the presence of concealed accessory pathway by intra-cavitary electrocardiographic test,among them 20 patients (group ⅠA) were ventricular pacing,the test results dis-played that S wave was followed by wide QRS complex exhibiting a pattern of right bundle branch block ( RBBB) ,SR interval was 0 s;SR intervals of 25 patients (groupⅠB) were not fixed,SR interval was (0.07 ±0.01)s,S wave had no concern with QRS wave ,the wide QRS complex was premature ventricular contraction ,QRS wave shapes were dif-ferent according to the different sites of pacing origin .(2)In groupⅡ,the test results displayed that S wave was close-ly followed by the atrial depolarization wave P ,and there was a wide QRS complex with pre-excitation wave at the be-ginning after a atrioventricular conduction time shorter than normal ,SR interval was fixed ,SR interval was (0.08 ±0. 03)s,at the same time,different parts of accessory pathway QRS complex had different morphological characteristics . (3) SR interval of ⅠA group compared with groupⅠB and groupⅡ,the differences were statistically significant ( t=2.97,3.02,all P0.05).Conclusion When TEAP displaying pacing wide QRS complex ,in order to avoid bringing misdiag-nosis,TEAP results should be analyzed comprehensively rather than blindly believing that the reason was concealed accessory pathway .

Analysis of RR-Lorenz Plot in Patients of Sinus Rhythm With Long RR Interval / 中国循环杂志

Objective: To explore the advantage of RR-Lorenz plot (RR-LP) in analyzing the patients of sinus rhythm with long RR interval. Methods: A total of 308 RR-LP patients with long RR interval were retrospectively studied. The patients were divided into 7 groups according to the type of long RR intervals. ① Sinus bradycardia with arrhythmia group, n=63,②Repeated transient sinus arrest group, n=16, ③Ⅱ° sino-atrial block group, n=14, ④Ⅱ° atrial ventricular block (Ⅱ° AVB) group, n=47, ⑤ Un-passed atrial premature beats (APB) group, n=28, ⑥ Atrial premature beats group, n=72 and ⑦ Premature ventricular beats group, n=68. We analyzed the patients of RR interval greater than 1500 ms with ambulatory electrocardiogram record. Results: ①RR-LP of sinus bradycardia with arrhythmia group showed a single distributing area with 1500 ms for the origin of transverse and longitudinal axis with B line slope at 1, tilt angle of 45°.②RR-LP of repeated transient sinus arrest,Ⅱ° sino-atrial block,Ⅱ° AVB and APB groups showed special four distributing areas with B line slope at (0.51 ± 0.01), tilt angle of (23.04 ± 0.50) °, B line slope at 0.6, tilt angle of (27°), B line slope at (0.57 ± 0.21), tilt angle of (25.69 ± 9.59)° and B line slope at (0.50 ± 0.01), tilt angle of (22.59 ± 0.54) ° respectively.③RR-LP of premature beats groups showed special four regional distributing areas, B line slope for atrial premature beats was at (0.38 ± 0.12), tilt angle of (17.06 ± 5.22) ° and B line slope for ventricular premature beats was at (0.07 ± 0.05), tilt angle of (3.02 ± 2.39) °. Conclusion: RR-LP in patients of sinus rhythm with long RR interval had speciifc morphology and distribution features, the local abnormality could be found in a plane via all RR intervals which provided a differential diagnosis for repeated occurrence of short RR interval.

Improved synthesis of raltegravir / 中国药科大学学报

Aim: To develop a practical synthetic route of raltegravir, a drug for HIV treatment. Methods: Raltegravir was synthesized through an eight-step process including aminonitrile formation, protection with benzyloxy-carbonyl group, conversion of the nitrile to the amidoxime, cyclization to form hydroxypyrimidinone, N-methyla-tion, amidation with microwave-assistance, deprotection, amidation with acyl chloride. Results: The overall yield of the eight-step synthesis is about 12. 0% and the structure of the target compound was confirmed by ~1H NMR, ~(13)C NMR, LR-MS and HR-MS. Conclusion: The reported synthetic process of raltegravir highlights the advantages in terms of readily available starting materials, convenient operation and low cost.

Analgesic effects of new triazole compounds Ⅱ_3 and their effects on the activity of cycloxygenase / 中国药科大学学报

Aim: To investigate the analgesic effect of the new triazole compounds Ⅱ_3 and effects on cycloxygen-ase-1(COX-1) as well as cycloxygenase-2( COX-2). Methods: The hot plate and the stretching settings in mice were utilized to study the effects of compounds Ⅱ_3 on acute pain. Radioimmunologic kits were used to assay the contents of PGE_2 in macrophage and 6-keto-PGF_(1α) in endodermis, which represents the activities of COX-2 and COX-1, respectively. Results: CompoundsⅡ_3( 15,30,60 mg/kg) prolonged the pain liminal value and the writ-hing response time in the initial appearance, and reduced the frequency of the writhing response in 15 min after exposure of the mice to glacial acetic acid( P < 0. 05, P < 0. 01). CompoundsⅡ_3, at the concentrations of 1×10 ~(-5),1×10 ~(-6), and 1×10 ~(-7) mol/L, markedly inhibited the production of PGE_2 in macrophage, and also impeded the activity of COX-2 at 1×10 ~(-6) mol/L But the inhibition of 6-keto-PGFla in endodermis using the same settings of compounds Ⅱ_3 was found to be limited. Conclusion: CompoundsⅡ_3 has analgesic effects on the acute pain and selective inhibition on COX-2.

STUDY ON EFFECT OF SKIN PENETRATION ENHANCER AZONE ON THE PENETRATION OF SEVERAL DRUGS THROUGH SKIN / 中国药理学通报

Azone ( 1桪odeylazacyclohenptan-2-one) is one of the best skin penetration enhancers. It can increase the permeability of skin for some hydrophobic compounds, so that it is possible to be admi-nistrated through skin. The effects of Azone on permeability of skin of a-Asarone, Nicorandil and Nitroglycerin were studied by flow through diffusion cell with radioactivity tracer.The results showed that the different concentrations of Azone gave different enhancement. The penetration of the 3 drugs was enhanced about 1-fold by