{"doi":"10.1021/jacs.5c07015","title":"Enzymatic Stereodivergent Synthesis of Azaspiro[2.y]alkanes","abstract":"Azaspiro[2.y]alkanes are increasingly valuable scaffolds in pharmaceutical drug discovery; however, an asymmetric catalytic method for their synthesis remains unknown. Here, we present a stereodivergent carbene transferase platform for the cyclopropanation of unsaturated exocyclic N -heterocycles to provide structurally diverse and pharmaceutically relevant azaspiro[2.y]alkanes in high yield (21–>99% yield) and excellent diastereoselectivity and enantioselectivity (diastereomeric ratio (dr) values from 52.5:47.5 to >99.5:0.5; enantiomeric ratio (er) values from 51:49 to >99.5:0.5). These engineered protoglobin-based enzymes operate on gram scale, with no organic cosolvent, at substrate concentrations up to 150 mM (25 g/L) using lyophilized E. coli lysate as the catalyst. This platform represents a practical, scalable, and stereodivergent biocatalytic synthesis of azaspiro[2.y]alkanes, using low-cost engineered protoglobins and their native iron-heme cofactors.","journal":"Journal of the American Chemical Society","year":2025,"id":518614,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9473,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":851624,"name":"Yueming Long","orcid":"0009-0006-5112-7791","position":1,"is_corresponding":false},{"id":1386517,"name":"Changhong Ko","orcid":null,"position":2,"is_corresponding":false},{"id":298858,"name":"Anuvab Das","orcid":"0000-0002-9344-4414","position":3,"is_corresponding":false},{"id":272467,"name":"Frances H. Arnold","orcid":"0000-0002-4027-364X","position":4,"is_corresponding":false},{"id":1211147,"name":"Jennifer L. Kennemur","orcid":"0000-0002-4835-1139","position":0,"is_corresponding":true}],"reference_count":30,"raw_metadata":null,"created_at":"2026-07-19T02:49:09.679930Z","pmid":"40694486","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":[]}