title: Total synthesis of (-)-virginiamycin M2: application of crotylsilanes accessed by enantioselective Rh(II) or Cu(I) promoted carbenoid Si-H insertion.
abstract: A stereoselective synthesis of the antibiotic (-)-virginiamycin M(2) is detailed. A convergent strategy was utilized that proceeded in 10 steps (longest linear sequence) from enantioenriched silane (S)-15. This reagent, which was prepared via a Rh(II)- or Cu(I)-catalyzed carbenoid Si-H insertion, was used to introduce the desired olefin geometry and stereocenters of the C1-C5 propionate subunit. A modified Negishi cross-coupling or an efficient alkoxide-directed titanium-mediated alkyne-alkyne reductive coupling strategy was utilized to assemble the trisubstituted (E,E)-diene. An underutilized late-stage SmI(2)-mediated macrocyclization was employed to construct the 23-membered macrocycle scaffold of the natural product.
authors: Department of Chemistry and Center for Chemical Methodology and Library Development, Metcalf Center for Science and Engineering, 590 Commonwealth Avenue, Boston University, Boston, Massachusetts 02215, USA.
authors: Jie
authors: J
authors: Wu
authors: James S
authors: JS
authors: Panek
mesh_terms: D000475:Alkenes / Q000737:chemistry; D000480:Alkynes / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D003300:Copper / Q000737:chemistry*; D003500:Cyclization; D006801:Humans; D006859:Hydrogen / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010084:Oxidation-Reduction; D012238:Rhodium / Q000737:chemistry*; D012821:Silanes / Q000737:chemistry*; D012825:Silicon / Q000737:chemistry*; D013237:Stereoisomerism; D014769:Virginiamycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis
chemical_list: D000475:Alkenes; D000480:Alkynes; D000900:Anti-Bacterial Agents; D012821:Silanes; C507609:crotylsilane; C522302:virginiamycin M2; D014769:Virginiamycin; D003300:Copper; D006859:Hydrogen; D012238:Rhodium; D012825:Silicon