{"doi":"10.1002/slct.202301435","title":"Synthesis of Chiral Tricyclic Pyrone Molecules via Palladium(0)‐Catalyzed Displacement Reactions of Chiral Tricyclic Pyrone Acetate With Azide or Amine","abstract":"Abstract Tricyclic pyrone (TP) molecules have shown protection of MC65 neuroblastoma cells death induced by amyloid‐β proteins through SβC gene, a decrease of amyloid‐β peptide levels, and improvement of motor functions and memory in Alzheimer's disease mouse and rat models. Mechanistic studies suggest TP molecules modulate N ‐methyl‐ D ‐aspartate receptor. A short synthesis of chiral TP analogs was sought using a Pd(0)‐catalyzed displacement of TP allylic acetate intermediate with sodium azide or substituted benzylamines. A three‐step sequence of reactions by the treatment of 2‐{(5aS,7S)‐3‐methyl‐1‐oxo‐1,5a,6,7,8,9‐hexahydropyrano[4,3‐b]chromen‐7‐yl}allyl acetate ( 9 ) with (Ph 3 P) 4 Pd and sodium azide, followed by reduction with Zn‐NH 4 OCHO and coupling with 3‐fluoro‐4‐hydroxybenzaldehyde and NaCNBH 3 was found to give TP coupling molecule, (5a S ,7 S )‐7‐(1‐(3‐fluoro‐4‐hydroxybenzylamino)prop‐2‐en‐2‐yl)‐3‐methyl‐6,7,8,9‐tetrahydropyrano[4,3‐b]chromen‐1(5a H )‐one ( 2 ), in a good yield. An alternative shorter pathway – a two‐step sequence of reactions – by the displacement of 9 by 4‐( t ‐butyldimethylsilyloxy)‐3‐fluoro‐benzylamine with a catalytic amount of (Ph 3 P) 4 Pd in THF followed by removal of the silyl ether protecting group gave 2 , albeit in a lower chemical yield. The described syntheses should provide general procedures for the synthesis of a library of TP molecules for the discovery of anti‐Alzheimer drugs.","journal":"ChemistrySelect","year":2023,"id":381864,"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":0.9516,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":953367,"name":"Zhaoyang Ren","orcid":"0000-0001-8817-9532","position":1,"is_corresponding":false},{"id":1147773,"name":"Huafang Fan","orcid":"0000-0001-7300-991X","position":2,"is_corresponding":false},{"id":826445,"name":"Duy H. Hua","orcid":"0000-0001-7179-0108","position":3,"is_corresponding":false},{"id":953810,"name":"Shunya Morita","orcid":null,"position":0,"is_corresponding":true}],"reference_count":23,"raw_metadata":null,"created_at":"2026-07-19T01:17:12.933204Z","pmid":"38045653","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":[]}