8GZB

SARS-CoV-2 3CLpro

Summary for 8GZB

• Entry DOI: 10.2210/pdb8gzb/pdb
• Descriptor: 3C-like proteinase nsp5, 1,2-ETHANEDIOL, 2-(4-chlorophenyl)-1,3,4-oxadiazole, ... (4 entities in total)
• Functional Keywords: inhibitor, complex, recombination, viral protein, hydrolase
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV,SARS-CoV-2)
• Total number of polymer chains: 1
• Total formula weight: 34068.21

Authors

Wang, F.,Cen, Y.X.,Tian, P. (deposition date: 2022-09-26, release date: 2023-09-27, Last modification date: 2024-10-09)

Primary citation

Li, Q.H.,Zhang, G.S.,Wang, F.,Cen, Y.,Liu, X.L.,Zhang, J.W.,Wang, Y.H.,Lee, A.W.M.,Gao, D.,Lin, G.Q.,Tian, P.
Nature-inspired catalytic asymmetric rearrangement of cyclopropylcarbinyl cation.
Sci Adv, 9:eadg1237-eadg1237, 2023

PubMed Abstract: In nature, cyclopropylcarbinyl cation is often involved in cationic cascade reactions catalyzed by natural enzymes to produce a great number of structurally diverse natural substances. However, mimicking this natural process with artificial organic catalysts remains a daunting challenge in synthetic chemistry. We report a small molecule-catalyzed asymmetric rearrangement of cyclopropylcarbinyl cations, leading to a series of chiral homoallylic sulfide products with good to excellent yields and enantioselectivities (up to 99% enantiomeric excess). In the presence of a chiral SPINOL-derived -triflyl phosphoramide catalyst, the dehydration of prochiral cyclopropylcarbinols occurs rapidly to generate symmetrical cyclopropylcarbinyl cations, which are subsequently trapped by thione-containing nucleophiles. A subgram-scale experiment and multiple downstream transformations of the sulfide products are further pursued to demonstrate the synthetic utility. Notably, a few heteroaromatic sulfone derivatives could serve as "covalent warhead" in the enzymatic inhibition of severe acute respiratory syndrome coronavirus 2 main protease.

PubMed: 37163601
DOI: 10.1126/sciadv.adg1237

Experimental method

X-RAY DIFFRACTION (2.7 Å)