Trends in organic chemistry最新文献

{"title":"Prioritizing natural product compounds using 1D-TOCSY NMR spectroscopy.","authors":"Cassandra Diaz-Allen,&nbsp;Richard W Spjut,&nbsp;A Douglas Kinghorn,&nbsp;Harinantenaina L Rakotondraibe","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Natural product (NP) secondary metabolites are designed evolutionarily to have biological effects in other organisms for defense and the mediation of ecological interactions. Their structural complexity and diversity complement biological systems, allowing them to display unique bioactivities. Although more than half of all pharmaceuticals stem from NPs, pharmaceutical companies have reduced NP-based drug discovery programs due to various time and cost-consuming pitfalls; the re-isolation of already known, bioactive compounds being one of the most common. Dereplication methods minimize cost and speed up the discovery of new, bioactive leads by quickly identifying known small molecules. Liquid chromatography coupled mass spectrometry (LC-MS) is the most widely utilized dereplication technique because of its sensitivity and the open-source availability of MS libraries. However, single-ionization techniques are not able to detect all metabolites in a biological sample. Even more concerning, bioactive isomers cannot be differentiated by their mass alone. In response to these issues, complementary dereplication tools are needed to assist MS. Total correlation spectroscopy (TOCSY) is an NMR experiment that illustrates the connection between all coupled protons in a spin system. Most molecules contain several spin systems, and together, these networks form a unique fingerprint that can be utilized to quickly differentiate and dereplicate known compounds, even those with identical masses. In addition, these fingerprints can be used to identify possible new compounds in a crude NP-extract that are structurally related to known small molecules. From a sample of the U.S. endemic lichen <i>Niebla homalea</i>, five non-cytotoxic, new triterpenoids and three known triterpenoids were isolated in our laboratory. As our goal is to discover both new and cytotoxic compounds, we developed a one-dimensional TOCSY-based dereplication method to quickly identify these non-bioactive triterpenoids. After prioritizing triterpenoid-free fractions that showed antiproliferative activity in various cancer cell lines, the new compound <b>11</b> was isolated from another <i>Niebla</i> species.</p>","PeriodicalId":75259,"journal":{"name":"Trends in organic chemistry","volume":"22 ","pages":"99-114"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9038091/pdf/nihms-1797830.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10251348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Classical tosylate/chloride leaving group approach supports a tetrahedral transition state for additions to trigonal carbon.","authors":"Malcolm J D'Souza,&nbsp;Jeremy Wirick,&nbsp;Jasbir Deol,&nbsp;Dennis N Kevill","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The experimentally measured rates of solvolysis of 2-chloroethoxycarbonyl chloride (2-chloroethyl chloroformate, <b>3)</b>, 2-chloroethoxycarbonyl <i>p</i>-toluenesufonate <b>(5)</b>, and phenoxycarbonyl <i>p</i>-toluenesulfonate (<b>6</b>) were followed at 25.0 °C in various pure and binary aqueous-organic solvents with varying degrees of polarity. An analysis of the rate constants for <b>3, 5</b>, and <b>6</b>, was carried out using the two-term extended Grunwald-Winstein equation and comparisons are made to the previously published results for ethyl and phenyl chloroformate esters. The <i>k</i> _OTS/<i>k</i> _Cl rate ratios and the Grunwald-Winstein <i>l/m</i> ratios indicate the probability of a dominant bimolecular carbonyl-addition pathway in the more nucleophilic solvents. Nevertheless in <b>3</b> and <b>5</b>, in the strongly hydrogen-bonding 70% and 50% HFIP mixtures, a side-by-side ionization mechanism is favored.</p>","PeriodicalId":75259,"journal":{"name":"Trends in organic chemistry","volume":"19 ","pages":"1-11"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366630/pdf/nihms-994812.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41161323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}