{"doi":"10.1039/d0ob02532a","title":"Design and synthesis of herboxidiene derivatives that potently inhibit <i>in vitro</i> splicing","abstract":"Herboxidiene is a potent antitumor agent that targets the SF3B subunit of the spliceosome. Herboxidiene possesses a complex structural architecture with nine stereocenters and design of potent less complex structures would be of interest as a drug lead as well as a tool for studying SF3B1 function in splicing. We investigated a number of C-6 modified herboxidiene derivatives in an effort to eliminate this stereocenter and, also to understand the importance of this functionality. The syntheses of structural variants involved a Suzuki-Miyaura cross-coupling reaction as the key step. The functionalized tetrahydrofuran core has been constructed from commercially available optically active tri-O-acetyl-d-glucal. We investigated the effect of these derivatives on splicing chemistry. The C-6 alkene derivative showed very potent splicing inhibitory activity similar to herboxidiene. Furthermore, the C-6 gem-dimethyl derivative also exhibited very potent in vitro splicing inhibitory activity comparable to herboxidiene.","journal":"Organic & Biomolecular Chemistry","year":2021,"id":206450,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9492,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":623762,"name":"Srinivasa Rao Allu","orcid":"0000-0001-9178-2578","position":1,"is_corresponding":false},{"id":772054,"name":"Guddeti Chandrashekar Reddy","orcid":null,"position":2,"is_corresponding":false},{"id":771491,"name":"Adriana López","orcid":"0000-0001-9169-800X","position":3,"is_corresponding":false},{"id":771492,"name":"Patricia Mendez","orcid":"0000-0001-5810-7669","position":4,"is_corresponding":false},{"id":565126,"name":"Melissa S. Jurica","orcid":"0000-0002-4488-1386","position":5,"is_corresponding":false},{"id":233704,"name":"Arun K. Ghosh","orcid":"0000-0003-2472-1841","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-18T23:51:41.571653Z","pmid":"33480941","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":[]}