{"doi":"10.1021/acs.joc.4c00686","title":"Second-Generation Chiral Amino Acid Derivatives Afford High Stereoselectivity and Stability in Aqueous RNA Acylation","abstract":"Activated acyl species have proven versatile in the esterification of 2'-OH groups in RNA, enabling structure mapping, caging, profiling, and labeling of the biopolymer. Nearly all reagents developed for this reaction have been achiral; however, a recent study reported that simple chiral amino acid acylimidazole derivatives could yield diastereoselective reactions at RNA 2'-OH in water, enabling up to 4:1 selectivity in screening. Here, we investigated the effect of steric bulk on the stereoselectivity of RNA reaction and on the stability of adducts with a library of 36 chiral acylimidazole scaffolds with increasing steric demand. The results document the highest stereoselectivity yet achieved in RNA acylation reactions, with as high as >99:1 diastereoselectivity at >70% conversion. Also notably, the bulky adducts were found to have markedly improved stability on RNA.","journal":"The Journal of Organic Chemistry","year":2024,"id":468128,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9415,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1044521,"name":"Sayantan Chatterjee","orcid":"0000-0001-9265-595X","position":1,"is_corresponding":false},{"id":329317,"name":"Lu Xiao","orcid":"0000-0003-1934-4711","position":2,"is_corresponding":false},{"id":1242284,"name":"Wenrui Zhong","orcid":"0000-0002-1236-0842","position":3,"is_corresponding":false},{"id":329319,"name":"Eric T. Kool","orcid":"0000-0002-7310-2935","position":4,"is_corresponding":false},{"id":1044522,"name":"Ryuta Shioi","orcid":"0000-0002-5050-4704","position":0,"is_corresponding":true}],"reference_count":30,"raw_metadata":null,"created_at":"2026-07-19T02:05:19.071498Z","pmid":"38809698","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}