Enhancing Efficiency of Natural Product Structure Revision: Leveraging CASE and DFT over Total Synthesis

被引:7
作者
Elyashberg, Mikhail [1 ]
Tyagarajan, Sriram [2 ]
Mandal, Mihir [2 ]
Buevich, Alexei V. [3 ]
机构
[1] Adv Chem Dev Inc, ACD Labs, Toronto, ON M5C 1B5, Canada
[2] Merck & Co Inc, Med Chem, Kenilworth, NJ 07033 USA
[3] Merck & Co Inc, Analyt Res & Dev, Kenilworth, NJ 07033 USA
来源
MOLECULES | 2023年 / 28卷 / 09期
关键词
natural products; structure revision; NMR; CASE; DFT; STRUCTURE ELUCIDATION; MYCELIAL CULTURES; MADURASTATIN C1; SAMOQUASINE-A; SESQUITERPENES; REASSIGNMENT; INHIBITORS; MBJ-0034; FUNGUS;
D O I
10.3390/molecules28093796
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Natural products remain one of the major sources of coveted, biologically active compounds. Each isolated compound undergoes biological testing, and its structure is usually established using a set of spectroscopic techniques (NMR, MS, UV-IR, ECD, VCD, etc.). However, the number of erroneously determined structures remains noticeable. Structure revisions are very costly, as they usually require extensive use of spectroscopic data, computational chemistry, and total synthesis. The cost is particularly high when a biologically active compound is resynthesized and the product is inactive because its structure is wrong and remains unknown. In this paper, we propose using Computer-Assisted Structure Elucidation (CASE) and Density Functional Theory (DFT) methods as tools for preventive verification of the originally proposed structure, and elucidation of the correct structure if the original structure is deemed to be incorrect. We examined twelve real cases in which structure revisions of natural products were performed using total synthesis, and we showed that in each of these cases, time-consuming total synthesis could have been avoided if CASE and DFT had been applied. In all described cases, the correct structures were established within minutes of using the originally published NMR and MS data, which were sometimes incomplete or had typos.
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页数:33
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