{"doi":"10.1002/anie.202117458","title":"Synthesis, Stereochemical Confirmation, and Derivatization of 12( <i>S</i> ),16ϵ‐Dihydroxycleroda‐3,13‐dien‐15,16‐olide, a Clerodane Diterpene That Sensitizes Methicillin‐Resistant <i>Staphylococcus aureus</i> to β‐Lactam Antibiotics","abstract":"Over the past decades, antibiotic resistance has grown to a point where orthogonal approaches to combating infections caused by resistant bacteria are needed. One such approach is the development of non-microbicidal small molecules that potentiate the activity of conventional antibiotics, termed adjuvants. The diterpene natural product 12(S),16ϵ-dihydroxycleroda-3,13-dien-15,16-olide, which we refer to as (-)-LZ-2112, is known to synergize with oxacillin against methicillin-resistant Staphylococcus aureus (MRSA). To explore this activity, (-)-LZ-2112 was synthesized and the structure confirmed through X-ray analysis. Preliminary structure-activity relationship studies following the synthesis of several analogs identified key structural elements responsible for activity and indicate that scaffold simplification is possible. A preliminary mode of action study suggests mecA plays a role in the adjuvant activity of (-)-LZ-2112.","journal":"Angewandte Chemie International Edition","year":2022,"id":263973,"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":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9528,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":922070,"name":"Gina M. Connors","orcid":null,"position":1,"is_corresponding":false},{"id":922071,"name":"Greg M. Durling","orcid":null,"position":2,"is_corresponding":false},{"id":799189,"name":"Allen G. Oliver","orcid":"0000-0002-0511-1127","position":3,"is_corresponding":false},{"id":231435,"name":"Lewis Marquez","orcid":"0000-0002-3782-5204","position":4,"is_corresponding":false},{"id":261028,"name":"Roberta J. Melander","orcid":null,"position":5,"is_corresponding":false},{"id":231438,"name":"Cassandra L. Quave","orcid":"0000-0001-9615-7886","position":6,"is_corresponding":false},{"id":258371,"name":"Christian Melander","orcid":"0000-0001-8271-4696","position":7,"is_corresponding":false},{"id":416563,"name":"Michael J. Zeiler","orcid":"0009-0001-0454-342X","position":0,"is_corresponding":true}],"reference_count":18,"raw_metadata":null,"created_at":"2026-07-19T00:26:37.567338Z","pmid":"35167718","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":[]}