{"doi":"10.3762/bjoc.20.195","title":"Deuterated reagents in multicomponent reactions to afford deuterium-labeled products","abstract":"The utility of bio-isosteres is broad in drug discovery and methodology herein enables the preparation of deuterium-labeled products is the most fundamental of known bio-isosteric replacements. As such we report the use of both [D 1 ]-aldehydes and [D 2 ]-isonitriles across 8 multicomponent reactions (MCRs) to give diverse arrays of deuterated products. A highlight is the synthesis of several FDA-approved calcium channel blockers, selectively deuterated at a t 1/2 limiting metabolic soft-spot via use of [D 1 ]-aldehydes. Surrogate pharmacokinetic analyses of microsomal stability confirm prolongation of t 1/2 of the new deuterated analogs. We also report the first preparation of [D 2 ]-isonitriles from [D 3 ]-formamides via a modified Leuckart–Wallach reaction and their use in an MCR to afford products with [D 2 ]-benzylic positions and likely significantly enhanced metabolic stability, a key parameter for property-based design efforts.","journal":"Beilstein Journal of Organic Chemistry","year":2024,"id":471825,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9522,"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":1306974,"name":"Shayna Maddern","orcid":null,"position":1,"is_corresponding":false},{"id":332004,"name":"Yueteng Zhang","orcid":"0000-0002-6882-196X","position":2,"is_corresponding":false},{"id":1178178,"name":"Grace E. Mastin","orcid":null,"position":3,"is_corresponding":false},{"id":1306975,"name":"Rachel Knight","orcid":null,"position":4,"is_corresponding":false},{"id":332006,"name":"Wei Wang","orcid":"0000-0001-6043-0860","position":5,"is_corresponding":false},{"id":394953,"name":"James J. Galligan","orcid":"0000-0002-5612-0680","position":6,"is_corresponding":false},{"id":1007555,"name":"Christopher Hulme","orcid":"0000-0001-6602-9613","position":7,"is_corresponding":false},{"id":1007554,"name":"Kevin Schofield","orcid":"0000-0002-2339-1433","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-19T02:05:48.788780Z","pmid":"39286789","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":[]}