哥倫比亞教授有機化學(xué)課件Glycosidation

1、GlycosidationOOOMeMeOPMBXXOTBSLecture NotesKey Reviews:K. C. Nicolaou, H. J. Mitchell, Angew. Chem. Int. Ed. 2001, 40, 1576.B. G. Davis, J. Chem. Soc., Perkin Trans. 1 2000, 2137.G.-J. Boons, Contemp. Org. Synth. 1996, 3, 173.G.-J. Boons, Tetrahedron 1996, 52, 1095.R. R. Schmidt in Comprehensive Org

2、anic Synthesis, Vol. 6,(Ed.: B. M. Trost, I. Fleming), Pergamon, Oxford, 1994, pp. 33 - 64.K. Toshima, K. Tatsuta, Chem. Rev. 1993, 93, 1503.Carbohydrates:The Main Players of the Family in the D-SeriesOHOOHHOHOOHglucoseOOHHOHOOHOHmannoseOHOOHHOHOOHalloseOHOOHHOHOOHgalactose8 total of this general fl

3、avor; these are the most common found in natural productsCarbohydrates:The Main Players of the Family in the D-SeriesOHOOHHOHOOHglucoseOOHHOHOOHOHmannoseOOHHOOHOHxyloserhamnoseOOHHOHOMeOHOHOOHHOHOOHalloseOHOOHHOHOOHgalactoseOH2NOHHOHOOHglucosaminefucoseOOHHOHOMeHO8 total of this general flavor; thes

4、e are the most common found in natural productsSome of the more exotic, but frequently incorporated, sugars in natural productsGlycosidations:Background and Key TerminologyOOOMeOOOMeOHHOMeOMeHOHOMeMeOMeOHOHMeOMeOMeMeMeOHOMeMeHOMeOMeL-rhamnoseOOHMeOHOHHOK. C. Nicolaou and co-workers, J. Am. Chem. Soc

5、. 1996, 118, 3059.Carbohydrates:A Unique Store of Chemical InformationH2NROOH3 amino acids = 6 linear combinations (2 x 2 x 2)Carbohydrates:A Unique Store of Chemical InformationH2NROOH3 amino acids = 6 linear combinations (2 x 2 x 2)NNNNNH2OOHOPOO-HOO-3 nucleosides = 6 linear combinations (2 x 2 x

6、2)Carbohydrates:A Unique Store of Chemical InformationH2NROOH3 amino acids = 6 linear combinations (2 x 2 x 2)NNNNNH2OOHOPOO-HOO-3 nucleosides = 6 linear combinations (2 x 2 x 2)OHOHOOHHOOH3 carbohydrates = 120 different combinations5 attachment points per sugar and Glycosidations:Background and Key

7、 TerminologyOORROORROOR1OORROORROOR1OORROROROOR1OORORROROOR151 Glycosidations:Background and Key TerminologyOORROROROXOORROROHOOR+glycosylacceptorglycosyldonorPromoterGlycosidations:Background and Key TerminologyOORROROROXOORROROHOOR+glycosylacceptorglycosyldonorOORROROROOOORROROOROORROROROOOORROROO

8、R Glycosidations:Control of Stereochemistry in the Koenigs-Knorr ReactionOXORORROROX = Cl, BrR = alkyl, benzylAg+or Hg+or Lewis acidOORROROROOORROROROOR1Formation of Glycosidations:Control of Stereochemistry in the Koenigs-Knorr ReactionFormation of Glycosidations:The Koenigs-Knorr ReactionW. Koenig

9、s, E. Knorr, Ber. 1901, 34, 957.OORROORROXOORROORROOR1or HgI2, HgBr2R1OH,AgClO4/SnCl2X = Br, ClClassical reaction, but typically not used today because:Glycosyl halides (Cl, Br, and I) are difficult to prepare, thermally unstable, and difficult to handle.A full equivalent of promoter is often requir

10、ed (i.e. lower donor reactivity).Glycosyl halides are easily hydrolyzed or eliminate.Glycosidations:The Koenigs-Knorr ReactionA. Furstner and co-workers, J. Org. Chem. 2000, 65, 8758.OOHOAcOOOMeOMeO1. Br2, P(OMe)32. AgOTf (1.8 equiv)OAcOOOMeOOOMeOOPMBPMBOPMBOOHOMeMe+OOPMBPMBOPMBOOOMeMe33OAcOOOMeOOAc

11、(89%)(100% Glycosidations:Use of Glycosyl Fluorides as Donor MoleculesFor another method using SelectFluor, see:C.-H. Wong and co-workers, J. Am. Chem. Soc. 1997, 119, 11743.OORROORROFOORROORROOR1or AgClO4/Cp2HfCl2or AgClO4/Cp2ZrCl2or BF3 Et2OR1OH,AgClO4/SnCl2High Glycosidations:Applications of Glyc

12、osyl Fluorides in SynthesisY. Takahashi, T. Ogawa, Carbohydrate Res. 1987, 164, 277.OOOBnOBnOOOBnOBnBnOHOBnOOOOBnOBnOFOBnOBnBnOAcOBnOglycosyl donorglycosyl acceptorSnCl2, AgOTf,Et2O,44 h, 20 C(80%, 1.8:1 Glycosidations:Applications of Glycosyl Fluorides in SynthesisY. Takahashi, T. Ogawa, Carbohydra

13、te Res. 1987, 164, 277.OOOBnOBnOOBnOOOBnOBnBnOOOOOOBnOBnOOBnOBnOBnOOBnOBnBnOOBnOBnBnOFOHOOOOHOHOOHOOOHOHHOOOOOOHOHOOHOHOHOOHOHHOOHOHHO Glycosidations:Applications of Glycosyl Fluorides in SynthesisY. Takahashi, T. Ogawa, Carbohydrate Res. 1987, 164, 277.OOOBnOBnOOBnOOOBnOBnBnOOOOOOBnOBnOOBnOBnOBnOOB

14、nOBnBnOOBnOBnBnOFOHOOOOHOHOOHOOOHOHHOOOOOOHOHOOHOHOHOOHOHHOOHOHHO Glycosidations:1,2-Migration Reaction to Install Glycosyl FluoridesK. C. Nicolaou and co-workers, J. Am. Chem. Soc. 1986, 106, 4189.OROORROXOHOROORROFX DAST, CH2Cl2OXO SFFNEt2OX(X = OMe, OAc, SPh, SePh, N3)1,2-migrationDAST = Et2NSF3

15、= (diethylamino)sulfur trifluorideORROROORROROFUseful way to install groups at C-2 that can serve as directing groups for the keyglycosidation step (OAc, SPh, SePh) and that can be subsequently removed to afford2-deoxysugars which are found in a variety of natural products (SPh)Glycosidations:Applic

16、ations of Glycosyl Sulfides in SynthesisFor a review, see: P. J. Garegg, Adv. Carb. Chem. Biochem. 1997, 52, 179.or NBSOORROORROSR1OORROORROOR2R1 = Et, Phor DMTST or IDCP or NIS/TfOH R2OH, Hg(OAc)2Formation:OORROORROOAcSR1Lewis acid(BF3 OEt2)In general, unless there is a C-2 directing group, glycosy

17、l sulfidesgive poor levels of anomeric stereocontrol.OORROORROSR1R1 = Et, PhDozens of preparative methods; this one is perhaps the most generalGlycosidations:Applications of Glycosyl Sulfides in SynthesisK. C. Nicolaou and co-workers, J. Am. Chem. Soc. 1982, 104, 2027.OMeTBSOMeOOMeSPhOMeOMeOOHOHMeMe

18、OOMeHOMeOOMeOO-mycinosyltylonideMeOAcMeHOOOEtOMeOAcMeOOMeHOMeOOMeOEt+NBS,CH3CN,25 C(85%)( Glycosidations:Applications of Glycosyl Sulfides in SynthesisK. C. Nicolaou and co-workers, J. Am. Chem. Soc. 1984, 106, 4189.SPhOMeMeOHOFOMeMeOTBSOOMeOMeOOMeMeOTBSOSPhSnCl2,AgClO4Et2O,(65%)30 min,-15 Glycosida

19、tions:Applications of Glycosyl Sulfides in SynthesisK. C. Nicolaou and co-workers, J. Am. Chem. Soc. 1984, 106, 4189.SPhOMeMeOHOFOMeMeOTBSOOMeOMeOOMeMeOTBSOSPhSnCl2,AgClO4Et2O,(65%)30 min,-15 Glycosidations:Applications of Glycosyl Sulfides in SynthesisK. C. Nicolaou and co-workers, J. Am. Chem. Soc

20、. 1984, 106, 4189.SPhOMeMeOHOFOMeMeOTBSOOMeOMeOOMeMeOTBSOSPhSnCl2,AgClO4Et2O,(65%)30 min,-15 Glycosidations:The Kahne-Crich Glycosidation ReactionD. Kahne and co-workers, J. Am. Chem. Soc. 1989, 111, 6881.D. Crich and co-workers, J. Am. Chem. Soc. 1998, 120, 435.OOROOOOROOSPhPhOOROOPhOR1PhOTfOOROROR

21、-78 CHOR1R1OHTTBP = 2,4,6-tri-t-butylpyrimidineTf2O,TTBPFormation:OOROOSPhPhOOROOROOSPhPhORmCPBA(1.0 equiv)One of best ways to make Glycosidations:The Kahne-Crich Glycosidation ReactionR. K. Boeckman and co-workers, J. Org. Chem. 1996, 61, 7984.Tf2O, DTBMP, CH2Cl2, -90C;MPM = methoxyphenylthiomethyl

22、OSOPhOMPMMPMOMPMOOMPMOMPMOMPMOMPMOOMPMOTfOTIPSMeHOMeOTIPSOTIPSOTIPSMeOMeOTIPSOTIPSOMPMOMPMOMPMOOMPMOMeOMeOHOHOOHHOHOOH(50%)(17:1 Glycosidations:The Kahne-Crich Glycosidation ReactionD. Crich and co-workers, J. Am. Chem. Soc. 1987, 52, 5487.OOOPhOBnSPMBOOPhTf2O, TTBP, CH2Cl2, -78 C;OOOPhOBnROOOBnOOBn

23、OMeBnOHOOBnOOBnOMeBnODDQ (83%)R = PMBR = H(88%, 11.6:1 Glycosidations:The Kahne-Crich Glycosidation ReactionD. Crich and co-workers, J. Am. Chem. Soc. 1987, 52, 5487.OOOPhOBnSPMBOOPhTf2O, TTBP, CH2Cl2, -78 C;OOOPhOBnROOOBnOOBnOMeBnOHOOBnOOBnOMeBnODDQ (83%)R = PMBR = H(88%, 11.6:1 Glycosidations:Use

24、of Trichloroacetimidates as Donor MoleculesOORROORROOCCl3NHOORROORROOR1R1OH,BF3 Et2Oor TMSOTfMechanism for displacement is essentially pure SN2Glycosidations:Use of Trichloroacetimidates as Donor MoleculesOORROORROOCCl3NHOORROORROOR1R1OH,BF3 Et2Oor TMSOTfMechanism for displacement is essentially pur

25、e SN2Formation:OORROORROOHNaH, DBU,or K2CO3Cl3CCNOORROORROOCCl3NHOORROORROOCCl3NHC-2 is a non-participating group Glycosidations:Use of Trichloroacetimidates as Donor MoleculesOORROORROOCCl3NHOORROORROOR1R1OH,BF3 Et2Oor TMSOTfMechanism for displacement is essentially pure SN2Formation:OORROORROOHNaH

26、, DBU,or K2CO3Cl3CCNOORROORROOCCl3NHOORROORROOCCl3NHC-2 is a non-participating group Glycosidations:Use of Trichloroacetimidates as Donor MoleculesW. R. Roush and co-workers, J. Am. Chem. Soc. 1999, 121, 1990.HOMeOMeOOOOHBOMOCAOOOBrSPhHOCAOTBSOTf, 4 MS,hexane/CH2Cl2 (1:1), -35 CHOMeOMeOOOOHBOMOCAOOO

27、BrPhSOOOOCAOOMeIHOMei-PrCO2BrPhSCAOOCAOOMeIHOMei-PrCO2BrONHCCl3PhS Glycosidations:Use of Trichloroacetimidates as Donor MoleculesK. C. Nicolaou and co-workers, J. Am. Chem. Soc. 1988, 110, 4660.OMeMeMeTBSOOOHCO2MeOMeOROROTBSOROROOTBSOAcON3OTBSMe+PPTS(40%)(100% Glycosidations:Use of Trichloroacetimid

28、ates as Donor MoleculesK. C. Nicolaou and co-workers, J. Am. Chem. Soc. 1993, 115, 7593.INHCO2MeOHOMeSSSHOOOHNOOOSMeOOMeOMeOOOHMeHOMeOHNMeOOHMeMeHOcalicheamicin Glycosidations:The Glycal MethodR. U. Lemieux and co-workers, Can. J. Chem. 1964, 42, 1473.OORROXROOR1ROOROORor PhSClor NISor DMDO, ZnCl2 P

29、hSeClor SelectfluorROOROORXR1OHTypically good control of anomeric stereochemistry;intermediate stereochemistry determined by substituents on glycal building blockGlycosidations:The Glycal MethodS. J. Danishefsky and co-workers, J. Am. Chem. Soc. 1987, 109, 8117.OMeOMeMeOHOOMeMeOAcOOMeOMeOOMeMeOTBSOO

30、Me Glycosidations:The Glycal MethodS. J. Danishefsky and co-workers, J. Am. Chem. Soc. 1987, 109, 8117.OMeOMeMeOHOOMeMeOAcOOMeOMeOOMeMeOTBSOOMe Glycosidations:A Case Study with Everninomicin 13,384-1Original isolation: A. K. Ganguly and co-workers, Heterocycles 1989, 28, 83.OOOOHOClClOMeMeOMeOMeNO2M

31、eMeOMeHOOMeOOHOOMeOHOMeOOOHOOOOOOOOOOOOMeOHMeHOOHMeMeOEGAHFCDA2A1Beverninomicin 13,384-1Obtained from bacteria found in a soil sample from the banks of the Nyiro River in KenyaActive against methicillin- and vancomycin-resistant strains of staphyloccocus aureus;currently in clinical development as a

32、n addition to our antibiotic arsenalPart of a larger class of antibiotics all possessing between 3 and 8 carbohydrate residuesGlycosidations:A Case Study with Everninomicin 13,384-1K. C. Nicolaou and co-workers, Chem. Eur. J. 2000, 6, 3095.OMeOTBSOHOTIPSMeOOOOPMBOTBSOSPhPhOMeOTBSMeOOOOTBSOTIPSOEE1.

33、Tf2O, DTBMP, CH2Cl2, -78 Glycosidations:A Case Study with Everninomicin 13,384-1K. C. Nicolaou and co-workers, Chem. Eur. J. 2000, 6, 3095.OOMeOBnOMeOOOBnORTIPSOOOMeOBnOMeOOBnOOOHTIPSOOOTBSOPMBPhSeHG1. SnCl2, Et2O, 0 Glycosidations:A Case Study with Everninomicin 13,384-1K. C. Nicolaou and co-worker

34、s, Chem. Eur. J. 2000, 6, 3095.OMeTBSOTBSOFSPhOMeTBSOTBSOOMeOBnOOPMBOPMBOMeHOBnOOPMBOPMB1. SnCl2, 4 MS, CH2Cl2/Et2O/Me2S (1:1:1), -10 C+2. Raney Ni, EtOH/THF (1:1), Glycosidations:A Case Study with Everninomicin 13,384-1K. C. Nicolaou and co-workers, Chem. Eur. J. 2000, 6, 3095.OMeOAcMeOHOPMBOOOMeOA

35、cMeOBF3 Et2O, CH2Cl2, -20 COMeOOAcOOMeOBnOMeOOOBnOOOOOOOHOPMBOOOMeOAcMeBnOOBnMeMeOEEG(55% Glycosidations:A Case Study with Everninomicin 13,384-1K. C. Nicolaou and co-workers, Chem. Eur. J. 2000, 6, 3095.OOOMeOMeBnOOOBnOClClOMeMeOOMeNO2MeMeSeOMeOOTBSOOMeOTBSOMeOOOTBSOOOOOOOHOOOOMeOTBSMeTBSOOTBSMeMeOEGPhCBA1AA2DHFOOOMeOMeBnOOOBnOClClOMeMeOOMeNO2MeMeSeFOMeOOTBSOOMeOTBSOMeOOOTBSOOOOOOOHOHOOOMeOTBSMeTBSOOTBSMeMeO