Domino Rh-catalyzed hydroformylation–doublecyclization of o-amino cinnamyl derivatives:applications to the formal total syntheses ofphysostigmine and physovenine

A parallel, versatile and efficient route to synthesis of pyrrolidinoindoline and tetrahydrofuranoindoline alkaloids from cinnamyl derivatives has been developed, featuring a domino Rh-catalyzed hydroformylation–double cyclization sequence. This method can be applied to the syntheses of anti-Alzheimer drugs such as physostigmine and physovenine

Devastating chest wall necrotizing fasciitis following pigtail catheter drainage

SummaryPigtail catheter for drainage of pleural effusion has gained popularity. Complication related to the insertion of these small-bore catheter is low. In this report, we highlight two cases with devastating necrotizing fasciitis of chest wall following pigtail catheter insertion

Prevalence of intestinal parasitic infections among school children in capital areas of the Democratic Republic of São Tomé and Príncipe, West Africa

Background: Although the Democratic Republic of Sao Tome and Principe (DRSTP) has undertaken school children-based deworming programs against intestinal parasitic infections (IPIs) using a single dose of mebendazole annually since 2005, it remains unclear as to the outcome to date. The present study intends to  investigate the recent IPIs status among school children living in capital areas of the DRSTP.Methods: A total of 252 school children (121 boys and 131 girls) of grades 4 and 5 from 4 primary schools located in the capital areas participated in the present study and their fresh fecal specimens were examined for the presence of any parasites using the merthiolate- iodine-formaldehyde concentration method as conducted.Results: The overall prevalence of IPIs was 64.7% (163/ 252). No significant gender difference in prevalence between boys (67.8%) and girls (61.8%) was found (p = 0.3). The majority of school children were infected with a single species of parasite (55.8%). Altogether, 12 different intestinal parasite species were identified in DRSTP school children, of which 9 species were pathogenic and the remaining 3 were non-pathogenic.Conclusion: Improving the detection method, sanitation facilities and personal hygiene as well as utilizing combined drugs are all important measures to greatly reduce IPIs in DRSTP school children.Keywords: Democratic Republic of Sao Tome and Principe, school children, intestinal parasitic infection

Clinical Efficacy and Post-Treatment Seromarkers Associated with the Risk of Hepatocellular Carcinoma among Chronic Hepatitis C Patients

This follow-up study enrolled chronic hepatitis C patients to evaluate the treatment efficacy and to identify post-treatment seromarkers associated with risk of hepatocellular carcinoma (HCC) among patients with a sustained virological response (SVR) or nonsustained virological response (NSVR). A total of 4639 patients who received pegylated interferon and ribavirin during 2004–2013 were followed until December 2014. HCC was confirmed through health examinations and data linkage with a national database. A total of 233 HCC cases were reported after 26,163 person-years of follow-up, indicating an incidence of 8.9 per 1000 person-years: 6.9 for SVR and 21.6 for NSVR per 1000 person-years. The associated risk of HCC in patients with SVR was 0.37 (0.22–0.63) for those without cirrhosis and 0.54 (0.31–0.92) for those with cirrhosis compared with their respective counterparts with NSVR. Among patients with SVR, advanced age, male gender, cirrhosis, decreased platelet count, and increased aspartate aminotransferase and α-fetoprotein levels were associated with HCC (p < 0.001). The treatment of chronic hepatitis C patients before they developed cirrhosis showed a higher efficacy than did the treatment of those who had already developed cirrhosis. Patients with SVR may still have a risk of HCC and need to be regularly monitored

Syntheses of piperidine alkaloid (–)-pelletierine, (–)-homopipecolic acid and indole alkaloid physostigmine

本篇論文主要為對含氮雜環生物鹼之合成路徑開發與反應條件探討。共分為二個部分，第一部分為吲哚植物鹼physostigmine之合成研究：將本實驗室一直以來致力研究的骨牌式氫甲醯化反應／雙環化反應，應用於雙胺基烯類衍生物70，進行骨牌式二次環合反應，建立三環hexahydropyrrolo[2,3-b]indoline的骨架71，並可應用於富有生物活性之植物鹼physostigmine及其衍生物的合成研究。 第二部分為哌啶植物鹼 (–)-pelletierine與 (–)-homopipecolic acid的合成研究：延續本實驗室已開發之胺基醇118和酮類120之製備，以Bayer-Villiger氧化反應得到內酯121，並還原得到哌啶結構衍生物122，並進一步合成植物鹼 (–)-homopipecolic acid及 (–)-pelletierine。Piperidine and indole alkaloids are medicinal compounds with potent biological activity activities. Here described syntheses of (–)-piperidine alkaloids (–)-pelletierine and (–)-homopipecolic acid, featuring a Bayer-Villiger oxidation of 6-tropanone as the key step; and synthetic studies on physostigmine and esermethole as applications of the Rh-catalyzed hydroformylation / double cyclization reaction.第一章 毒扁豆鹼之合成研究 1 1.1 毒扁豆鹼之簡介 1 1.2 利用氫甲醯化反應進行骨牌式反應 10 1.2.1 縮醛 10 1.2.2 縮醛胺 13 1.2.3 亞胺 13 1.2.4 烯胺 14 1.3 研就動機 16 1.4 結果與討論 18 1.4.1 逆合成分析 (一) 18 1.4.2 合成探討(一) 19 1.4.3 逆合成分析 (二) 27 1.4.4 合成探討(二) 28 1.5 結論 33 第二章 手性2,6-二取代哌啶衍生物之合成研究 34 2.1 2,6-二取代哌啶衍生物之介紹 34 2.2 結果與討論 37 2.3 結論 45 實驗部份 46 儀器測定與試劑 46 實驗部步驟 48 參考文獻 79 附錄一 Syntheses of (−)-pelletierine and (−)-homopipecolic acid 13

Syntheses of (−)-pelletierine and (−)-homopipecolic acid

Enantiomeric syntheses of (−)-homopipecolic acid and (−)-pelletierine have been achieved by chiral resolution of tropanol followed by Baeyer–Villiger oxidation. The methodology provides a practical route for the synthesis of optically pure piperidines

Rhodium-Catalyzed Hydrocarbonylation of a Homoallylamine via N–H Activation and Application for Synthesis of Yohimbane Alkaloids

We describe syntheses of <i>n</i>-yohimbane and alloyohimbane using Rh-catalyzed hydrocarbonylation, which provides a practical methodology to synthesize a δ-lactam from a secondary homoallyl amine. We have also observed an unexpected transformation where the amine proton served as a hydride to participate in hydrocarbonylation. The D-labeled experimental results and preliminary DFT-calculations suggest that the transformation can be rationalized by oxidative cleavage of the homoallyl amines to a metal hydride complex

Synthesis of Aryl Thioethers Through the NCS-Promoted Cross-Coupling Reaction of Thiols with Grignard Reagents

A convenient one-pot approach for the synthesis of aryl sulfides through the coupling of thiols with Grignard reagents in the presence of N-chlorosuccinimide is described. The sulfenylchlorides were formed when thiols were treated with N-chlorosuccinimide, and the resulting sulfenylchlorides were then directly reacted with Grignard reagents to provide aryl sulfides in good to excellent yields under mild reaction conditions. Functional groups including ester, fluoro and chloro are tolerated by the reaction conditions employed. It is important to note that this method has a short reaction time (30 min in total), and represents an alternative approach for the synthesis of aryl sulfides over the existing protocols

DNA Hypomethylation Is Associated with the Overexpression of INHBA in Upper Tract Urothelial Carcinoma

Urothelial carcinoma includes upper urinary tract cancer (UTUC) and bladder cancer. Although nephroureterectomy is the standard treatment for UTUC, the recurrence rate is approximately half and the tumor is associated with poor prognoses. Metastases are the most devastating and lethal clinical situation in urothelial carcinoma. Despite its clinical importance, few potential diagnostic biomarkers are suitable for early UC detection. We compared high-stage/high-grade urothelial carcinoma tissues to adjacent normal urothelial tissues using methyl-CpG binding domain protein capture for genome-wide DNA methylation analysis. Based on our findings, inhibin βA (INHBA) might be associated with carcinogenesis and metastasis. Further, clinical UC specimens had significant INHBA hypomethylation based on pyrosequencing. INHBA was detected by real-time PCR and immunohistochemistry staining, and was found to be highly expressed in clinical tissues and cell lines of urothelial carcinoma. Further, INHBA depletion was found to significantly reduce BFTC-909 cell growth and migration by INHBA-specific small interfering RNA. Interestingly, a positive correlation was found between SMAD binding and extracellular structure organization with INHBA using gene set enrichment analysis and gene ontology analysis. Together, these results are the first evidence of INHBA promoter hypomethylation and INHBA overexpression in UTUC. INHBA may affect urothelial carcinoma migration by reorganizing the extracellular matrix through the SMAD pathway

Alkyne-mediated domino hydroformylation/double cyclization: mechanistic insight and synthesis of (+/-)-tashiromine

A novel domino reaction, alkyne-mediated domino hydroformylation/double cyclization, has been developed for rapid preparation of indolizidine type alkaloids. DFT calculations were applied for rationales of reactivity and selectivity. A concise synthesis of tashiromine as the application of the methodology is also reported