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Total synthesis, structure revision and cytotoxic activity of Sch 53825 and its derivatives

The first total synthesis of Sch 53825 (14) was achieved in 12 steps from 5-hydroxy-1-tetralone in 16% overall yield through N-benzyl cinchoninium chloride-catalyzed asymmetric epoxidation and a Mitsunobu reaction as the key steps. On this basis, the synthesis of palmarumycin B(6) was improved using...

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Autores principales: Xu, Leichuan, Ma, Haoyun, An, Xinkun, Li, Yihao, Zhang, Qian, Liu, Xinlei, Wang, Mingan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9194939/
https://www.ncbi.nlm.nih.gov/pubmed/35765427
http://dx.doi.org/10.1039/d2ra02898k
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author Xu, Leichuan
Ma, Haoyun
An, Xinkun
Li, Yihao
Zhang, Qian
Liu, Xinlei
Wang, Mingan
author_facet Xu, Leichuan
Ma, Haoyun
An, Xinkun
Li, Yihao
Zhang, Qian
Liu, Xinlei
Wang, Mingan
author_sort Xu, Leichuan
collection PubMed
description The first total synthesis of Sch 53825 (14) was achieved in 12 steps from 5-hydroxy-1-tetralone in 16% overall yield through N-benzyl cinchoninium chloride-catalyzed asymmetric epoxidation and a Mitsunobu reaction as the key steps. On this basis, the synthesis of palmarumycin B(6) was improved using the same raw material with 6 steps and 32% overall yield. Also, three new analogues with two chlorine atoms were synthesized. Their structures were characterized by (1)H, (13)C NMR, HR-ESI-MS and X-ray diffraction data. The structure of natural Sch 53825 was revised as an epimer of compound 1 with the anti-hydroxy epoxide at C-4. Their cytotoxic activities against several tumor cell lines (HCT116, U251, BGC823, Huh-7 and PC9) showed that compound 11 exhibited excellent cytotoxicity against above mentioned cancer cell lines with IC(50) < 0.5 μM.
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spelling pubmed-91949392022-06-27 Total synthesis, structure revision and cytotoxic activity of Sch 53825 and its derivatives Xu, Leichuan Ma, Haoyun An, Xinkun Li, Yihao Zhang, Qian Liu, Xinlei Wang, Mingan RSC Adv Chemistry The first total synthesis of Sch 53825 (14) was achieved in 12 steps from 5-hydroxy-1-tetralone in 16% overall yield through N-benzyl cinchoninium chloride-catalyzed asymmetric epoxidation and a Mitsunobu reaction as the key steps. On this basis, the synthesis of palmarumycin B(6) was improved using the same raw material with 6 steps and 32% overall yield. Also, three new analogues with two chlorine atoms were synthesized. Their structures were characterized by (1)H, (13)C NMR, HR-ESI-MS and X-ray diffraction data. The structure of natural Sch 53825 was revised as an epimer of compound 1 with the anti-hydroxy epoxide at C-4. Their cytotoxic activities against several tumor cell lines (HCT116, U251, BGC823, Huh-7 and PC9) showed that compound 11 exhibited excellent cytotoxicity against above mentioned cancer cell lines with IC(50) < 0.5 μM. The Royal Society of Chemistry 2022-06-14 /pmc/articles/PMC9194939/ /pubmed/35765427 http://dx.doi.org/10.1039/d2ra02898k Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Xu, Leichuan
Ma, Haoyun
An, Xinkun
Li, Yihao
Zhang, Qian
Liu, Xinlei
Wang, Mingan
Total synthesis, structure revision and cytotoxic activity of Sch 53825 and its derivatives
title Total synthesis, structure revision and cytotoxic activity of Sch 53825 and its derivatives
title_full Total synthesis, structure revision and cytotoxic activity of Sch 53825 and its derivatives
title_fullStr Total synthesis, structure revision and cytotoxic activity of Sch 53825 and its derivatives
title_full_unstemmed Total synthesis, structure revision and cytotoxic activity of Sch 53825 and its derivatives
title_short Total synthesis, structure revision and cytotoxic activity of Sch 53825 and its derivatives
title_sort total synthesis, structure revision and cytotoxic activity of sch 53825 and its derivatives
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9194939/
https://www.ncbi.nlm.nih.gov/pubmed/35765427
http://dx.doi.org/10.1039/d2ra02898k
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