Enantioselective Synthesis ofOasomycin A, Part II: Synthesisof the C29-C46 SubunitAngew. Chem., Int. Ed. 2007, 46, 541-544Evans, D.A.; Nagorny, P.; Reynolds, D.J.; McRae K.J.Presented by: James Hale, 04-16-2007Discovery and Biological Implications• Produced by Streptoverticillium andStreptomyces strains (Streptomycesolivaceus Tu 4081).• Potential antibiotic and inhibitor ofcholesterol biosynthesis.5189150 Feb, 1993 Zeeck et al. 536/6.Retrosynthesis: Oasomycin AOHOH OHM eM eOH OH O H OH OHOHOMeOOOM eM eOHM eHOMe M eOHMeOHoasomy cin AMeOR O RM eOR OR ORM eOOOMeOROR O R OOM eOM eMeO RMeROM e M eORMeORO ROR O RCHOM eO RMeROM eOMeOM eM eORMeORO2SNNNNPhC29-C46C13-28C1-C12C1-C28Ang. Chem., Int. Ed. 2007, 2007, 46, 545-548Retrosynthesis: C29-C46 FragmentM eOR ORMeOR OR O RMeOOOSO2NOO RORNNNNP hPhPhR OHOORORORMeORM eO NBnOO OM e MeHOR OROROSynthesis: C29-C38 Fragmentt-BuOOR1OR1HOBnONCuN NO OPh Ph2+2 SbF6-1, CH2Cl2, -95oC1t-BuOOBnO O OH1. Me4NBH(OAc)3, MeCN/AcOH, -25oC2. TBSCl, Imi, DMF, RT3. DIBALH, C6H5Me, -90 to -78oCHOBnO R1R1ONOO OMeMeSn(OTf)2, NEt3, CH2Cl2-20 to -78oCOBnOR1OR1OH95:5 dr91:9 dr95% eeXcO OMeMeR1 = TBSBnSynthesis: C29-C38 FragmentOBnR1R1OHXcO OMeMe1. Me4NBH(OAc)3, MeCN/AcOH, -20 to -78oC2. TBSOTf, lutidine, CH2Cl2, 0oCOBnOR1OR1OR1XcO OHMeMe1. LiBH4, THF, H2O, 0oC2. PMPCH(OMe)2, PPTS, CH2Cl2, 0oC3. Sc(OTf)3, BH3/THF, CH2Cl2, 0oCOBnOR1OR1OR1OR2MeMeHO1. TESOTf, Lutidine, THF, 0oC2. Pd(OH)2/C, H2, EtOAc3. DMP, Py, CH2Cl2OR1OR1OR1OR2MeMeTESOOHR1 = TBSR2 = PMBSynthesis: C39-C46 FragmentNOPhPhH1. n-BuLi, THF, -78oC2. DMF, -78 to 20oCNOPhPhOHCONOBnOMe1. MgCl2, TMSCl, NEt3, EtOAc, 77oC2. TFA, MeOH3. Pd/C, H2, EtOAc4. TESOTf, lutidine, CH2Cl2, 0oCONOBnOMe NOPhPhOTES1. EtSLi, THF, -20oC2. DIBALH, CH2Cl2, -90oC3. PPh3=CHCO2Et, CH2Cl2MeNOPhPhOTESEtO2C13:1 d.r.3. PPh3=CHCHO, CH2Cl2Synthesis: C39-C46 FragmentMe NOPhPhOTESEtO2C1. HCl, MeOH2. PMPCHO, KOtBu, Et2O/toluene, -20oCMe NOPhPhOEtO2COPMP94:6 d.r.1. LiAlH4, Et2O, 0oC2. 1-phenyl-1H-tetrazole-5-thiol, DEAD, Ph3, THF3. (NH4)6Mo7O24, H2O2, EtOHMe NOPhPhOOPMPSO2NNNNPh1. AlBr3, EtSH, CH2Br2/CH2Cl22. TMSCl, imidazole, CH2Cl2Me NOPhPhORORSO2NNNNPhR = TMSSynthesis: C29-C46 FragmentMe NOPhPhOR1OR1SO2NNNNPhR1 = TMSTESOHMeOR2OR3MeOR3OR3OR2 = PMBR3 = TBS1. KHMDS, DME, -48 to -20oC2. PPTS, MeOH/CH2Cl2HOMeOR2OR3MeOR3OR3NOPhPhOHOHMeR2 = PMBR3 = TBSSynthesis: C29-C46 FragmentR2 = PMBR3 = TBSHOMeOR2OR3MeOR3OR3NOPhPhOHOHMeRose Bengal, O2, hv(CH2Cl)2NOBzBzOHOHMeR2 = PMBR3 = TBSHOMeOR2OR3MeOR3OR3OHMeOO1. TMSCl, imidazole, CH2Cl22. PPTS, Py, MeOH/CH2Cl23. DMP, Py, CH2Cl2R1 = TMSR2 = PMBR3 = TBSMeOR2OR3MeOR3OR3OR1MeOOOConclusion• Subunit C29-C46 of oasomycin A wassynthesized with high enantioselectivity.• Enantioselective aldol reactions werehighly utilized for the formation of C29-C38and C39-C46 subunits.• Julia-Kocienski olefination used as a keystep in the formation of the
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