{"title":"TNBC 选择性细胞毒性溴代异壬烷 PC-A 的全合成及其初步结构-活性关系。","authors":"Sayaka Maeda, Wakana Nakayama, Yohei Saito, Momoko Sagano, Masuo Goto and Kyoko Nakagawa-Goto*, ","doi":"10.1021/acs.jnatprod.3c01075","DOIUrl":null,"url":null,"abstract":"<p >PC-A (<b>1</b>), a bromo nor-eremophilane, showed selective antiproliferative activity against a triple-negative breast cancer (TNBC) cell line. This unique activity prompted us to establish a total synthesis to facilitate a structure–activity relationship (SAR) study and selectivity optimization. An enantioselective first total synthesis of <b>1</b> was achieved starting from (<i>R</i>)-carvone through a side chain extension with a Mukaiyama aldol reaction and decalin construction. The synthesized decalin derivatives and debromo PC-A (<b>2</b>) were evaluated for antiproliferative activity against five human tumor cell lines, including TNBC, to assess preliminary SAR correlations.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":null,"pages":null},"PeriodicalIF":3.3000,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Total Synthesis of a TNBC-Selective Cytotoxic Bromo Nor-eremophilane, PC-A, and Its Preliminary Structure–Activity Relationships\",\"authors\":\"Sayaka Maeda, Wakana Nakayama, Yohei Saito, Momoko Sagano, Masuo Goto and Kyoko Nakagawa-Goto*, \",\"doi\":\"10.1021/acs.jnatprod.3c01075\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >PC-A (<b>1</b>), a bromo nor-eremophilane, showed selective antiproliferative activity against a triple-negative breast cancer (TNBC) cell line. This unique activity prompted us to establish a total synthesis to facilitate a structure–activity relationship (SAR) study and selectivity optimization. An enantioselective first total synthesis of <b>1</b> was achieved starting from (<i>R</i>)-carvone through a side chain extension with a Mukaiyama aldol reaction and decalin construction. The synthesized decalin derivatives and debromo PC-A (<b>2</b>) were evaluated for antiproliferative activity against five human tumor cell lines, including TNBC, to assess preliminary SAR correlations.</p>\",\"PeriodicalId\":47,\"journal\":{\"name\":\"Journal of Natural Products \",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2024-03-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Natural Products \",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acs.jnatprod.3c01075\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Natural Products ","FirstCategoryId":"99","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.jnatprod.3c01075","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Total Synthesis of a TNBC-Selective Cytotoxic Bromo Nor-eremophilane, PC-A, and Its Preliminary Structure–Activity Relationships
PC-A (1), a bromo nor-eremophilane, showed selective antiproliferative activity against a triple-negative breast cancer (TNBC) cell line. This unique activity prompted us to establish a total synthesis to facilitate a structure–activity relationship (SAR) study and selectivity optimization. An enantioselective first total synthesis of 1 was achieved starting from (R)-carvone through a side chain extension with a Mukaiyama aldol reaction and decalin construction. The synthesized decalin derivatives and debromo PC-A (2) were evaluated for antiproliferative activity against five human tumor cell lines, including TNBC, to assess preliminary SAR correlations.
期刊介绍:
The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained.
Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.
When new compounds are reported, manuscripts describing their biological activity are much preferred.
Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.