title: Stereoselective photochemical 1,3-dioxolane addition to 5-alkoxymethyl-2(5H)-furanone: synthesis of bis-tetrahydrofuranyl ligand for HIV protease inhibitor UIC-94017 (TMC-114).
abstract: A convenient synthesis of (3R,3aS,6aR)-3-hydroxyhexahydrofuro[2,3-b]furan, a high-affinity nonpeptidal ligand for HIV protease inhibitor UIC-94017, is described. This inhibitor is undergoing advanced clinical trials. The synthesis utilizes a novel stereoselective photochemical 1,3-dioxolane addition to 5(S)-benzyloxymethyl-2(5H)-furanone as the key step. The requisite furanone derivative was prepared in high enantiomeric excess by an immobilized lipase-catalyzed selective acylation of (+/-)-1-(benzyloxy)-3-buten-2-ol and a ring-closing olefin metathesis with Grubbs' catalyst. Optically active bis-THF was converted to protease inhibitor 2 (UIC-94017).
authors.affiliation: Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street,Chicago, Illinois 60607, USA. arunghos@uic.edu
authors.forename: Arun K
authors.initials: AK
authors.lastname: Ghosh
authors.forename: Sofiya
authors.initials: S
authors.lastname: Leshchenko
authors.forename: Marcus
authors.initials: M
authors.lastname: Noetzel
mesh_terms: D002384:Catalysis; D000069454:Darunavir; D004148:Dioxolanes / Q000737:chemistry*; D005663:Furans / Q000138:chemical synthesis*; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007202:Indicators and Reagents; D008024:Ligands; D015394:Molecular Structure; D013237:Stereoisomerism; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: C494001:(3R,3aS,6aR)-3-hydroxyhexahydrofuro(2,3-b)furan; D004148:Dioxolanes; D005663:Furans; D017320:HIV Protease Inhibitors; D007202:Indicators and Reagents; D008024:Ligands; D013449:Sulfonamides; D000069454:Darunavir