The Career Of Stuart Schreiber Part 1: Organic Chemist
The Career of Stuart SchreiberPart 1: Organic ChemistGroup Meeting: April 1, 2009Benjamin D Horning For a complete listing of Dr. Schreiber’s publications, including pdf links, please visithttp://www.broad.harvard.edu/chembio/lab hp
The (Chemistry) Career of Stuart L. SchreiberBiographical Notes Education (b. 1956 - Virginia)B.A. : University of Virginia (1977); R. J. Sundberg – Photocyclization of Indole DerivativesPh.D.: Harvard (1981); R. B. Woodward and Y. Kishi – oxidation of tertiary amines Hydrgogen Transfer from Tertiary Amines to Trifluoroacetic Anhydride. Tetrahedron 1980, 21, 1027 Fragmentation Reactions of α-alkoxy Hdroperoxides and Application to the Synthesis of ( )-Recifeiolide. J. Am. Chem. Soc. 1980, 102, 6163 Oxidation of Tertiary Amines. II. Peroxides in Organic Synthesis. Ph.D. Thesis, Harvard University, 1981 CareerAssistant Professor (1981-84); Associate Professor (tenured) (1984-86); Professor (1986-88); Department of Chemistry, YaleProfessor (1988-1998); Morris Loeb Professor (1998-); Department of Chemistry and Chemical Biology, HarvardDepartment Chair (2001-2004); Director, Chemical Biology, and Founding Core Member of the Broad Institute of HarvardAnd MIT (2003-); Investigator, Howard Hughes Medical Institute (1994-); Affiliate, Department of Cell Biology,Harvard Medical School (1994-2004); Member, Graduate Programs in Biophysics and Immunology (1988-), Harvard CompaniesFounder, Forma Therapeutics, Inc. (2008-); Founder, Co-Chair of the Scientific Advisory Board, Infinity Pharmaceuticals(2002-06); Founder and Chair of the Board of Scientific and Medical Advisers, ARIAD Pharmaceuticals (1991-); Founder,ARIAD Gene Therapeutics (1994-2008); Founder and Scientific Advisory Board Member, Vertex Pharmaceuticals (1988-90);Adviser, Theravance, 2000-04; Consultant, Pfizer, 1983-91 Notable Awards (chemistry)Dreyfus Newly Appointed Faculty Award, 1981; Searle Scholar, 1982; Dreyfus Teacher-Scholar Award, 1985; Fellow of the Alfred P. Sloan Foundation,1985; NSF Presidential Young Investigator Award, 1985; ICI Pharmaceuticals Award for Excellence in Chemistry, 1986; Arthur C. Cope Scholar Award,American Chemical Society (ACS), 1986; Award in Pure Chemistry, ACS, 1989; Arun Guthikonda Memorial Award, Columbia University, 1990; ThiemeIUPAC Award in Synthetic Organic Chemistry, 1992; NIH Merit Award, 1992, Rhone-Poulenc Silver Medal, Royal Society of Chemistry, 1992; Award forCreative Work in Synthetic Chemistry, ACS, 1994; Elected to the National Academy of Sciences and the American Academy of Arts & Sciences, 1996 Publications: 425 invited lectures 400 publications (h-index 109)http://www.broad.harvard.edu/chembio/lab schreiber/members/smdbSchreiberBio.php
The (Chemistry) Career of Stuart L. SchreiberH-indexAd Bax is theonly livingchemist whois bothyounger andhas a s/2007/April/23040701.asp
The (Chemistry) Career of Stuart L. SchreiberEx-Group Members Amir Hoveyda (1981-1986) (Ph.D.)Dissertation: “The Furan-Carbonyl Photocycloaddition Reactionand its Applications in Organic Synthesis”Currently Joseph T. Vanderslice Professor, Boston College Tim Jamison (1992-1997) (Ph.D.)Dissertation: “I. Consecutive Use of Two Reactions of AlkyneCo2(CO)6Complexes in the Total Synthesis of ( )-EpoxydictymeneII. Studies Directed Toward the Synthesis of theDiazonamide Marine Natural Products tly Paul M. Cook Career Development AssociateProfessor ofChemistry, MIT Glenn Micalizio (2000-2003) (post-doc)Currently Associate Professor, Scripps Florida James Morken (1995-1997) (post-doc)Currently Professor, Boston College John A. Porco Jr. (1985-1992) (Ph.D.)Dissertation: “Studies Toward the Synthesis of the Enediyne Antibiotics”Currently Assistant Professor of Chemistry, Boston University Daniel Romo (1991-1993) (post-doc)Currently Professor, Texas A&M University Scott Rychnovsky (1987-1988) (post-doc)Currently Professor, University of California, Irivine Matthew Shair (1995-1997) (post-doc)Currently Professor, Harvard University Martin Burke (2000-2004) (Ph.D.)Currently Assistant Professor, University of Illinois, Urbana-Champaign John Wood (1991-1993) (post-doc)Currently A.I. Meyers Professor of Chemistry, Colorado State University Marc Snapper (1990-1993) (post-doc)Currently Professor, Boston Collegehttp://www.broad.harvard.edu/chembio/lab schreiber/smdb/smdbFormerMembersForm.php
The (Chemistry) Career of Stuart L. SchreiberTimeline Research theme:To develop chemical transformations that can be used as springboardsfor the synthesis of complex natural rat Yale1989Type II Diels-Aldertowards Calichemicin1984Total Synthesis rahedron Letters 1989, 30,3765JACS 1984, 106, 40381982Ozonolytic cleavage ofcycloalkenes to terminallydifferentiated products1986Macrolide epoxidationstrategy towardsMonensinMeCHOCH(OR)2OMeOO1993First Synthesis of DiscodermolideMeHMeKOH, HCl,HOacetoneOMe OMeOMeCO2MeJACS 1986, 108, 2106MeOOTetrahedron Letters 1982, 23, 3867HOOMeOMeMeMeMeHMeMeMeOHOCONH2OHOHJACS 1993, 115, 12621
The (Chemistry) Career of Stuart L. SchreiberOutlineCHO The use of α-alkoxy hydroperoxides in organic synthesisOSchreiber OzonolysisORMeAlkene Baeyer-VilligerOOR'Macrolide synthesisROOOHOMeO Utilization of [2 2} photocycloaddition reactions in total synthesisMePeriplanone BOOFuran Paterno-Büchi, “photoaldol”OOTotal synthesis of Asteltoxin Verging on enamine ”CHOOHMeNt-BuOPh
α-Alkoxy Hydroperoxides in Organic SynthesisSchreiber OzonolysisO3OCH(OMe)2OMeMeOH,MeOH,OMePTSAO OOworkupCHO
α-Alkoxy Hydroperoxides in Organic SynthesisSchreiber OzonolysisO3OCH(OMe)2OMeMeOH,MeOH,OMePTSAO OOworkupCHO
α-Alkoxy Hydroperoxides in Organic SynthesisSchreiber OzonolysisO3, ROH,CHOAc2O,CHOEt3NNaHCO3ROO3, ROH,OOHCH(OR)2OAc2O,ORCH(OR)2Et3NPTSAROO3, ROH,OOHCH(OR)2ONaHCO3ORCH(OR)2Me2SPTSAROOOHCHO
α-Alkoxy Hydroperoxides in Organic SynthesisSchreiber OzonolysisO3, ROH,CHOAc2O,CHOEt3NNaHCO3ROO3, ROH,OOHCH(OR)2OAc2O,ORCH(OR)2Et3NPTSAROO3, ROH,OOHCH(OR)2ONaHCO3ORCH(OR)2Me2SPTSAROOOHCHO
α-Alkoxy Hydroperoxides in Organic SynthesisSchreiber OzonolysisO3, ROH,CHOAc2O,CHOEt3NNaHCO3ROO3, ROH,OOHCH(OR)2OAc2O,ORCH(OR)2Et3NPTSAROO3, ROH,OOHCH(OR)2ONaHCO3ORCH(OR)2Me2SPTSAROOOHCHO
α-Alkoxy Hydroperoxides in Organic SynthesisSchreiber OzonolysisO3, ROH,CHOAc2O,CHOEt3NNaHCO3ROO3, ROH,OOHCH(OR)2OAc2O,ORCH(OR)2Et3NPTSAROO3, ROH,OOHCH(OR)2ONaHCO3ORCH(OR)2Me2SPTSAROOOH Ozonolysis modification allows access to terminally differentiated productsSchreiber et al. Organic Synthesis 1984, 64, 168 and Schreiber et al. Tetrahedron, 1982, 23, 38676CHO
α-Alkoxy Hydroperoxides in Organic SynthesisSchreiber Ozonolysis Differentially substituted alkenes can be selectively functionalizedOAcOAcO3, MeOH,OAcretro 2 3O1,3 additionCHOONaHCO3OAcOOOCHOof methanolOOHOMe Ester formation depends upon hydride migrationRHOOOOMeORSchreiber et al. J. Am. Chem. Soc. 1983, 105, 660ROORHOROOMeHOORMe
α-Alkoxy Hydroperoxides in Organic SynthesisBaeyer-Villiger Criegee rearrangement of alkoxy-hydroperoxides derived from 1,1-disubstituted olefinsMeO3, CPBAOMeSchreiber et al. Tetrahedron 1983, 24, 2363OOOOMe
α-Alkoxy Hydroperoxides in Organic SynthesisBaeyer-Villiger Criegee rearrangement of alkoxy-hydroperoxides derived from 1,1-disubstituted olefinsMeO3, CPBAOMeSchreiber et al. Tetrahedron 1983, 24, 2363OOOOMe
α-Alkoxy Hydroperoxides in Organic SynthesisIron/Copper mediated peroxide reduction/fragmentation Reduction of intermediate alkoxy hydroperoxides generates a highly fragmentable radical speciesMeO3, ,AcOHFe2 !Fe3 MeMeOOHOMeOMeSchreiber et al. J. Am. Chem. Soc. 1980, 102, 6163Cu(OAc)2OOMeOMe-AcOMeMeOCu(OAc)2
α-Alkoxy Hydroperoxides in Organic SynthesisIron/Copper mediated peroxide reduction/fragmentation Reduction of intermediate alkoxy hydroperoxides generates a highly fragmentable radical speciesMeO3, ,AcOHFe2 !Fe3 MeMeOOHOMeOMeSchreiber et al. J. Am. Chem. Soc. 1980, 102, 6163Cu(OAc)2OOMeOMe-AcOMeMeOCu(OAc)2
α-Alkoxy Hydroperoxides in Organic SynthesisApplication in macrolide synthesis Fragmentation of cyclic alkoxy-hydroperoxides can yield macrocyclesLDA, Me3Al, MeOHOOH2O2, cifeiolide Single olefin regio- and geometrical olefin isomer observedHMeOCuO HSchreiber et al. J. Am. Chem. Soc. 1980, 102, 6163HHH
α-Alkoxy Hydroperoxides in Organic SynthesisApplication in macrolide synthesis Fragmentation of cyclic alkoxy-hydroperoxides can yield macrocyclesLDA, Me3Al, MeOHOOH2O2, cifeiolideHMeOCu Single olefin regio- and geometrical olefin isomer observedO HHMeOCuO HSchreiber et al. J. Am. Chem. Soc. 1980, 102, 6163HHHHHH
[2 2] photocycloaddition reactions in natural product synthesisPeriplanone BOOOMeMe Cockroach sex pheromone, used by female cockroaches to stimulate males by olfactory communication Isolation ( 1μg/insect) achieved by via dissection of 35,000 cockroach alimentary tracts and extraction of midguts,as well as fecal recovery and extraction from an additional 20,000 cockroaches, yielded 200 μg Periplanone B First synthesis and relative stereochemistry by W. C. Still in 1979 Cyclodecanone structure containing two epoxides (one spirocyclic), two olefins and an isopropyl substituent First step scaleable (10.6g), involves photocycloadditionSchreiber et al. J. Am. Chem. Soc. 1984, 106, 4038
[2 2] photocycloaddition reactions in natural product synthesisPeriplanone BOOOMe Schreiber plans on utilizing a similar end-game as found in the Still SynthesisMeOOOMeMeSchreiber et al. J. Am. Chem. Soc. 1984, 106, 4038
[2 2] photocycloaddition reactions in natural product synthesisPeriplanone BOOOMe Schreiber plans on utilizing a similar end-game as found in the Still eMeMeMeMeMeCorey-ChaykovskygrignardadditionOMe OHOMeHMeHMe[2 2] PhotocycloadditionSchreiber et al. J. Am. Chem. Soc. 1984, 106, 4038HMeHMe
[2 2] photocycloaddition reactions in natural product synthesisPeriplanone BOOOMe A clever synthon for a eMeMeMeelectrocyclic ring openingolefin OMe OHOMeHMeHMe[2 2] PhotocycloadditionSchreiber et al. J. Am. Chem. Soc. 1984, 106, 4038HMeHMe
[2 2] photocycloaddition reactions in natural product synthes enolization/trapping allows desired olefin installationMeOLHMDS,MeMeSPhOOMeOH, NaIO4;Me-78 C;PhSSO2Ph16:1 selectivityMeMePhMe, 110 C32% (3 steps)MeOHOHMeHOMeCSchreiber et al. J. Am. Chem. Soc. 1984, 106, 4038HC
[2 2] photocycloaddition reactions in natural product synthesisPeriplanone BOOOMe A series of oxidations (utilizing peripheral attack) installs the remaining functionalityMeOOOOt-BuOOH, KHMeLHMDS, THF;Me83%MeMeOMeHHOMe(Me)3SI, NaH,OMeMeSchreiber et al. J. Am. Chem. Soc. 1984, 106, 4038H2O2, THF, 97%THF, Ac2O, NaOAc;MeOH, H2O,K2CO3, 60%MeOO Synthesis is completed in 13 steps, 2% yieldMeOMeHMePhSeBr83%OHSePhOOOODMSO, THF,62%MeMe
[2 2] photocycloaddition reactions in natural product synthesisFuran-aldehyde photocycloaddition, “photoaldol”Ph OOH Hh!PhOOH Paterno-Büchi reaction between a furan and an aldehyde proceeds with good head-to-head and exo- selectivity Products serve as protected threo aldol products between a 1,4-dicarbonyl and an aldehyde Unfortunately, only symmetrically substituted furans are serviceable; Unsymmetrically subsituted ones proceed withlow chemoselectivity Products serve as protected threo aldol products between a 1,4-dicarbonyl and an aldehydeSchreiber et al. J. Am. Chem. Soc. 1983, 105, 660
[2 2] photocycloaddition reactions in natural product synthesisFuran-aldehyde photocycloaddition, “photoaldol” OH SA,MeOHMeR'RMeOPhPhMeHOmCPBAMePhHR H, R' MeR Me, R' HH 2,Rh/Al2O3HOBH3 THF;H2O2MeOOMeBH HMeBPhOOMeRMeBH2HSchreiber et al. J. Am. Chem. Soc. 1983, 105, 660HR'PhOORHMe HArCO2OOOMeOHOHR' HHOOBPhR' HORBOOH Me PhH2OMeHPhOOMeBH2HPhOHMe
[2 2] photocycloaddition reactions in natural product synthesisAsteltoxinHOMeMeMe OHOOOHOAsteltoxinMeOMe Stereochemically complex bis-tetrahydrofuran region connection by an all-trans triene linker to a pyrone region Inhibitor of oxidative phosphorylation, serves as a fluorescent probe of mitochondrial F1- and bacterial BF1-ATPase No total synthesis prior to 1984 Relative stereochemistry (and vicinal methyl groups) lends to construction via furan-aldehyde Paterno-BüchiSchreiber et al. J. Am. Chem. Soc. 1983, 105, 6723 and Schreiber et al. J. Am. Chem. Soc. 1984, 106, 4186
[2 2] photocycloaddition reactions in natural product synthesisAsteltoxinHOMeMeMe OHOOOHOAsteltoxinMeOMeHOMeMeCHOOOMeHOMeMeOHMe OHMe OOOHOO MeOMeOOMeMeSchreiber et al. J. Am. Chem. Soc. 1983, 105, 6723 and Schreiber et al. J. Am. Chem. Soc. 1984, 106, 4186OMeMe
[2 2] photocycloaddition reactions in natural product synthesisAsteltoxinHOMeMe OHROMeOHMeMeMeOBn Oh!, PhHOOBnMe HOOmCPBA,Springboard stepScaleableUsed to set all , CSA55% (2 steps)OOHTHF : 3N HCl3:1OBnMeOBnMe HArCO2NaHCO345% (2 steps)HHOMeMeHOHOHHOHOHEtMgBr, THFOBnOHMeHOMeOMeHNNMe2XX OX NNMe2Schreiber et al. J. Am. Chem. Soc. 1983, 105, 6723 and Schreiber et al. J. Am. Chem. Soc. 1984, 106, 4186OBnMe2NNH2,MgSO472% (2 steps)
[2 2] photocycloaddition reactions in natural product synthesisAsteltoxinHOMeMe eMeCuSO4, CSA55% (2 steps)HOHHOHOHEtMgBr, THFOBnOHMeHOMeOMeHNNMe2XX OX NNMe2Schreiber et al. J. Am. Chem. Soc. 1983, 105, 6723 and Schreiber et al. J. Am. Chem. Soc. 1984, 106, 4186OBnMe2NNH2,MgSO472% (2 steps)
[2 2] photocycloaddition reactions in natural product synthesisAsteltoxinHOMeMe OHRMeOOHBuLi, THF, PhSClOHOSPhSchreiber et al. J. Am. Chem. Soc. 1983, 105, 6723 and Schreiber et al. J. Am. Chem. Soc. 1984, 106, 4186OSPh
[2 2] photocycloaddition reactions in natural product synthesisAsteltoxinHOMeMe OHROMeOHHOMeMeMeOOOHR BnR HORMeOHOMe1. ArSeCn, PBu3,THFMeOMe2. H2O2, THF81% (2 steps)MeOOHMeHOMeO3, CH2Cl2,MeMeOH, Me2S92%Li, NH398%MeOOMeOHHOHOMeMe OHCSASOPhMeO77%MeOOMeOOHHSOPhSchreiber et al. J. Am. Chem. Soc. 1983, 105, 6723 and Schreiber et al. J. Am. Chem. Soc. 1984, 106, 4186MeBuLi, THF88% (3:1)SOPhHOMeMeMeMe
[2 2] photocycloaddition reactions in natural product synthesisAsteltoxinHOMeMe OHROMeOHHOMeMeORMeOOOHHOMe1. ArSeCn, PBu3,THFMe2. H2O2, THF81% (2 steps)OMeOHMeMeMeOH, Me2S92%Li, NH398%R HHOMeO3, CH2Cl2,OMeMeR eOOHSOHOHOMeMeOMeMeMeSchreiber et al. J. Am. Chem. Soc. 1983, 105, 6723 and Schreiber et al. J. Am. Chem. Soc. 1984, 106, 4186OOHMeBuLi, THF88% (3:1)PhOMeMeMe
[2 2] photocycloaddition reactions in natural product synthesisAsteltoxinHOMeMe OHROMeOHHOMeMeMeOOOHR BnR HORMeOHOMe1. ArSeCn, PBu3,THFMeOMe2. H2O2, THF81% (2 steps)MeOOHMeHOMeO3, CH2Cl2,MeMeOH, Me2S92%Li, NH398%MeOOMeOHHOHOMeMe OHCSASOPhMeO77%MeOOMeOOHHSOPhSchreiber et al. J. Am. Chem. Soc. 1983, 105, 6723 and Schreiber et al. J. Am. Chem. Soc. 1984, 106, 4186MeBuLi, THF88% (3:1)SOPhHOMeMeMeMe
[2 2] photocycloaddition reactions in natural product synthesisAsteltoxinHOMeMe OHRMeOOHBuLi, THF, PhSCOHOSOSPhPhOMeO1. MeI, K2CO3,acetoneOMe2. NaNH2, NH3,Et2O, CO2OO1. CDI, THFOCO2HMeMe2. (MeO)2SO2, K2CO3,acetoneSchreiber et al. J. Am. Chem. Soc. 1983, 105, 6723 and Schreiber et al. J. Am. Chem. Soc. 1984, 106, 4186MeOMeMe
[2 2] photocycloaddition reactions in natural product synthesisAsteltoxinHOMeMe OHRMeOOHHOMeMe OHOMeHOMe1. CF3CO2COCH3,Ac2O, 2,6-lutOHSOPh2. HgCl2, CaCO3,CH3CN, H2O60%OHOOLDA, HMPA,OOMeO80%THFOMeMeHOMeOMeOMeMe OHMeMe OHHOMeMe OHTsCl, DMAP,MeOOOHOMeOMeEt3N, CH2Cl282%MeOSchreiber et al. J. Am. Chem. Soc. 1983, 105, 6723 and Schreiber et al. J. Am. Chem. Soc. 1984, 106, 4186OOHHOOMeOMe
[2 2] photocycloaddition reactions in natural product synthesisAsteltoxinHOMeMeMe OHOOOHOAsteltoxinMeOMe Synthesis completed in 16 steps, 4% overall yield Key steps include a furan-aldehyde Paterno-Büchi, several diastereoselective additions to aldehydes, and anaddition/double 2,3-rearrangement to give net dienal addition Symmetrically substituted furan partner a necessary retrosynthetic fragmentSchreiber et al. J. Am. Chem. Soc. 1983, 105, 6723 and Schreiber et al. J. Am. Chem. Soc. 1984, 106, 4186
[2 2] photocycloaddition reactions in natural product synthesisUnsymmetrically substituted furan partners OH Hh!PhOPhOOHR2 R1OH Hh!R1OOOH HPh HOOHR1R1 SiMe31.2:1R1 Sii-Pr320:1R1 SnBu32.5:1R1 SnBu320:1Schreiber et al. Tetrahedron Letters. 1988, 29, 6689Ph(CO2Bu instead of Ph)
Verging on enamine catalysisDiastereoselective enal/enone intramolecular 4 2R1R2R2 H R3R3OHCR4MeNHPhR4OOO3, MeOH;66gPTSA; NaHCO3,Me2SR1 r et al. J. Am. Chem. Soc. 1986, 108, 8274 and Schreiber et al. J. Am. Chem. Soc. 1988, 110, 5198
Verging on enamine catalysisDiastereoselective enal/enone intramolecular 4 2Starting materialproductyieldd.r.73 25:160 25:1604:1( 25:1 after 10h)8614:1( 25:1 after 10h)8410:1( 25:1 after (Me)PhSchreiber et al. J. Am. Chem. Soc. 1986, 108, 8274 and Schreiber et al. J. Am. Chem. Soc. 1988, 110, 5198
Verging on enamine catalysisComparison with more recent studiesHCHOH1 eq. MeNHPhOCHOEt2OMeTBDPSOCHOMeHTBDPSOH0.3 eq. .3 eq. D-prolineDMSON(Me)PhOO83% yieldOMeHTBDPSOH91% yield0.3 eq. L-prolineDMSO87% yieldOCHOMe86% yield14:1 dr( 25:1 after 10h)OMeHOHSchreiber et al. J. Am. Chem. Soc. 1988, 110, 5198 and MacMillan et al. J. Am. Chem. Soc. 2005, 127, 3696
Verging on enamine catalysisInduction of asymmetryH1. O3, MeOH; Me2SCHO2. 1N HCl, acetoneCHOMe HNEt2O, rtt-BuPhOO75%HMe3:2 cis:transNt-BuOPht-BuCHO MeNt-BuOSchreiber et al. J. Am. Chem. Soc. 1988, 110, 5198NCHO OPhMePh17:1 cis:trans
Verging on enamine catalysisSynthesis of Brefeldin COHHSH1. m-CPBA; NaBH4OHMeNOH2. 1N HCl31% (2 steps)H1. HS(CH2)2SH, TiCl4SHCHO OTHPSO2PhMe2. NaIO4, aq. t-BuOH3. DBU, 14% (3 steps)CHOt-BuO1. BuLi, BF3 OEt22. Na(Hg), MeOH48% (2 steps)3. PTSA, MeOH, 83%PhBu Bu Bu BuSCN Sn O Sn OHHO Sn OSnNCSSBu Bu Bu BuCHOH1. PhMe, !OMeIOSchreiber et al. J. Am. Chem. Soc. 1988, 110, 51982. MeI, aq. acetone76% (2 steps)ICO2Me SHOHMe
Verging on enamine catalysisSynthesis of Brefeldin COHOMeOHHBrefeldin COCHOHCrCl2, 0.1% wt/wtOMeIONi(acac)2, DMF60%HOMeOHH4:1 d.r. atalcohol(wrong way)OCHOHCrCl2, 0.1% wt/wtOMeSchreiber et al. J. Am. Chem. Soc. 1988, 110, 5198IONi(acac)2, DMF70%HOMeOHH10:1 d.r. atalcohol
Stay tuned for part II: Stuart Schreiber, biologist Stuart Schreiber worked alongside the best in the field during the 1980s His synthetic work continued into the 1990s, though his focus switched mostly to biology His synthetic work continues today, but is focused on the synthesis of small molecules of biological interest
The use of α-alkoxy hydroperoxides in organic synthesis Schreiber Ozonolysis Alkene Baeyer-Villiger Macrolide synthesis Utilization of [2 2} photocycloaddition reactions in total synthesis Periplanone B Furan Paterno-Büchi, "photoaldol" Total synthesis of Asteltoxin Verging on enamine catalysis O O O R OOH OR' CHO O OR O Me O O Me MeO O O .
May 02, 2018 · D. Program Evaluation ͟The organization has provided a description of the framework for how each program will be evaluated. The framework should include all the elements below: ͟The evaluation methods are cost-effective for the organization ͟Quantitative and qualitative data is being collected (at Basics tier, data collection must have begun)
Silat is a combative art of self-defense and survival rooted from Matay archipelago. It was traced at thé early of Langkasuka Kingdom (2nd century CE) till thé reign of Melaka (Malaysia) Sultanate era (13th century). Silat has now evolved to become part of social culture and tradition with thé appearance of a fine physical and spiritual .
On an exceptional basis, Member States may request UNESCO to provide thé candidates with access to thé platform so they can complète thé form by themselves. Thèse requests must be addressed to esd rize unesco. or by 15 A ril 2021 UNESCO will provide thé nomineewith accessto thé platform via their émail address.
̶The leading indicator of employee engagement is based on the quality of the relationship between employee and supervisor Empower your managers! ̶Help them understand the impact on the organization ̶Share important changes, plan options, tasks, and deadlines ̶Provide key messages and talking points ̶Prepare them to answer employee questions
Dr. Sunita Bharatwal** Dr. Pawan Garga*** Abstract Customer satisfaction is derived from thè functionalities and values, a product or Service can provide. The current study aims to segregate thè dimensions of ordine Service quality and gather insights on its impact on web shopping. The trends of purchases have
Chính Văn.- Còn đức Thế tôn thì tuệ giác cực kỳ trong sạch 8: hiện hành bất nhị 9, đạt đến vô tướng 10, đứng vào chỗ đứng của các đức Thế tôn 11, thể hiện tính bình đẳng của các Ngài, đến chỗ không còn chướng ngại 12, giáo pháp không thể khuynh đảo, tâm thức không bị cản trở, cái được
Le genou de Lucy. Odile Jacob. 1999. Coppens Y. Pré-textes. L’homme préhistorique en morceaux. Eds Odile Jacob. 2011. Costentin J., Delaveau P. Café, thé, chocolat, les bons effets sur le cerveau et pour le corps. Editions Odile Jacob. 2010. Crawford M., Marsh D. The driving force : food in human evolution and the future.
Le genou de Lucy. Odile Jacob. 1999. Coppens Y. Pré-textes. L’homme préhistorique en morceaux. Eds Odile Jacob. 2011. Costentin J., Delaveau P. Café, thé, chocolat, les bons effets sur le cerveau et pour le corps. Editions Odile Jacob. 2010. 3 Crawford M., Marsh D. The driving force : food in human evolution and the future.
