Organic Chemistry from the Eastern Bloc Baran Lab GM 08/13/2011 Florina Voica Major Research Centers: Institute of Organic Chemistry, Polish Academy of Sciences Univ of Warsaw Adam Mickiewiecz Univ, Poznan Warsaw Univ of Technology Gdansk Technical Univ Founding fathers: Osman Achmatowicz (1899-1988) - alkaloids isolation (O. Achmatowicz Jr - sugar chemistry, name rxn) Jerzy Suszko (1889-1972) - polycyclic aromatics Edwin Plazek - heterocyclic chemistry Henryk Kuczynski (1909-1991) - terpene chemistry O OSitBuPh 2 H TMS SO 2 Ph nBuLi then MsCl 86% (over 2 steps) TMS PhO 2 S OSitBuPh 2 OMs dr 3:1 PhO 2 S OSitBuPh 2 TMS LDA, THF 89% TBAF 41% OH Tet. Lett. 1991, 32, 531 SO 2 Ph O TMS nBuLi, then HClO 4 , MeOH OH OH O (+)DET, Ti(OiPr) 4 , TBHP 1. TsCl, pyr 2. (nC 9 H 19 ) 2 CuLi C 9 H 19 O (+)-disparlure Tet. Lett. 1989, 30, 2845 O O Me Me O O Me O Me O H Me O OH 1. NaOMe, 40% 2. H 2 , Pd/SrSO 3 H 2 , Pd/C Me O H Me O OH H 1. L-selectride 2. N 2 H 4 3. I 2 Me H Me HO OH H I N 2 H 2 Me H Me HO OH H I Me H Me THPO OH H O Me 1. tBuNC, NaCNBH 3 Bu 3 SnCl, AIBN 2. DHP 3. MeLi, PhH Me H Me THPO OH H O O 1. LDA, MoOHPy 2. Ph 3 P • • O J. Org. Chem. 1988, 53, 4855 Prof. Jerzy Wicha - born on February 14, 1936, Warsaw, Poland; - education: M. Sc.: Moscow State University, 1958 Ph. D.: The University of Warsaw, 1964 D. Sc.: The University of Warsaw, 1970 - positions: 1958-1960 Research Associate, Institute of Pharmaceutical Industry, Warsaw 1960 -1970 Instructor - reader, the University of Warsaw 1970 - 1978 Docent, Institute of Organic Chemistry, Polish Academy of Sciences 1978 - Professor, the same Institute - 184 publications (Scifinder) - major research topics: steroid synthesis, some guanacastepene, prostaglandins research, some methods based on the Julia olefination reaction. Organic Chemistry from the Eastern Bloc Baran Lab GM 08/13/2011 Florina Voica Me Me H H THPO O Me Me H H THPO HO TMS Br TMS nBuLi, BF 3 •Et 2 O 93% Me Me H H THPO O TMS O O F 3 C O Me Me H H THPO O O Me Me H H THPO O OH OH Me Me OH H HO O O Digitoxigenin 1.VO(acac) 2 , TBHP, 86% 2. mCPBA, 87% 3. TFAA, pyr, 87% TBAF, H 2 O, THF, rt J. Org. Chem. 1995, 60, 1823 Me OMe Me CO 2 Et Me OMe Me EtO 2 C Br Br Br Me OMe Me Me Br Me OMe Me Me Br Br Br Me OMe Me Me Me Me Me Me Me HO LDA/THF, -78 °C then iPr 80% 1. DIBAL 2. TsCl, pyr 3. Superhydride 80% CHBr 3 -50%NaOH CETRIMID 50%, dr 1:1 (separable) MeLi/Et 2 O -78 °C to rt then MeI, -78 °C to rt 60% TsOH/aq dioxane 23-H-isocalysterol (both diastereoisomers are NPs) J. Am. Chem. Soc. 1995, 117, 1849 Organic Chemistry from the Eastern Bloc Baran Lab GM 08/13/2011 Florina Voica For more on steroid functionalization: J. Org. Chem. 2010, 75, 5388, J. Org. Chem. 1990, 55, 3484, Tetrahedron 1989, 45, 2223, Tet. Lett. 1988, 29, 4001, J. Org. Chem. 1973, 38, 1280. For some representative refs on formal syntheses of different vitamin Ds (20 papers published)- Tet. Lett. 1998, 29, 885, Synthesis 1999, 1209; J. Org. Chem. 2007, 72, 5276. For work on terpene synthesis: Tet. Lett. 2005, 46, 1149, J. Org. Chem. 2010, 75, 8337. Prof. Mieczyslaw Makosza - born in 1934 - education: M. Sc : Univ.of Leningrad, 1958 Ph.D : Technical Univ. Warsaw, 1956 D.Sc : Technical Univ. Warsaw, 1971 - positions: 1975-1977, Director, Institute of Organic Chemistry and Technology, Univ. of Warsaw 1979-present, Director, Institute of Organic Chemistry, Polish Academy of Sciences. - 420 publications (Scifinder) - major research areas: phase transfer catalysis (chemistry of carbanions and carbenes), vicarious nucleophilic substitution. Vicarious Nucleophilic Substitution of Hydrogen (VNS) - describes the reaction of a nucleophile with a electrophilic arene (nitroarenes, heteroarenes) or alkene; - the attack can occur ortho or para to the NO 2 group but there are ways to achieve selectivity; disubstituted prods are usually not observed; - VNS is an "umpolung Friedel-Crafts" reaction and it complements the scope of the FC rxn since it allows functionalization of arenes which are very poor nucleophiles in S E Ar. General reaction scheme: NO 2 X R Y base solvent + NO 2 - Y R X base -HX Y R NO 2 - NO 2 Y R H + Z = F, Cl, Br, I, OMe, OPh, SMe, Et, tBu, Ph, NMe 2 , CF 3 , CN, SO 2 Me, CO 2 H. Y (EWG) = SO 2 Ph, SO 2 NH 2 , CN, CO 2 Et, Cl, Ar etc. X (good LG) = Cl, Br, OPh, SPh etc. Typical base: KOH, NaOH, tBuOK. Typical solvent : DMSO, DMF, THF, MeOH, NH 3 (l). Extensive reviews on the topic: Acc. Chem. Res. 1987, 20, 282; Synthesis 1991, 103; Chem. Soc. Rev. 2010, 39, 2855; for VNS examples on electrophilic olefins: Tetrahedron 1991, 47, 5001; for an exhaustive review on VNS on heterocycles: Chem. Rev. 2004, 104, 2631. NO 2 NC Me Ph + OH Me Ph NC tBuOK DMF/THF -70 °C DMDO, H 2 O aq. NH 4 Cl 83% J. Org. Chem. 1998, 63, 4390 N N N N SO 2 Ph N N SO 2 Ph SO 2 Ph Cl SO 2 Ph KOH, DMSO 66% OH MeO NO 2 NO 2 Synthesis 1997, 1131 OH MeO NO 2 NO 2 CN OMe MeO NO 2 NO 2 CN OMe MeO NO 2 NO 2 CN CO 2 Et PhO CN tBuOK, DMF 80% Me 2 SO 4 , NaHCO 3 83% Br CO 2 Et 69% H N HN O OMe MeO H 2 , PdCl 2 -Fe 48% H N HN O O O Damirone B Chem. Lett. 1987, 61 NO 2 N Me SO 2 Ph N Me SO 2 N + Ph TBSO O - N Me SO 2 Ph NO N Me SO 2 Ph N TBSO N N Me SO 2 TBSO N N Me SO 2 DBU TBSCl DBU -TBSOH DBU TBSCl hν DBU -TBSOH Acta Chem. Scand. 1992, 46, 689 Organic Chemistry from the Eastern Bloc Baran Lab GM 08/13/2011 Florina Voica Phase transfer catalysis: A process in which a phase transfer catalyst (usually a tetraalkylammonium salt, QX ++ ) facilitates the reaction of inorganic and organic anions or carbenes with organic electrophiles. Practically, it consists of a two-phase mixture: the inorganic solution containing reacting anions or base that will generate organic anions; the organic mixture containg the organic reactants and the phase transfer catalyst (source of lipophilic cations). General reaction scheme: - reactive inorganic anions: Na + Y - aq + Q + X - org Na + Y - aq + Q + X - org Q + Y - org + RX Q + X - org + RY - in situ generated organic anions: PhCH 2 CN org + Na + OH - aq PhCH - CN org Na + int + H 2 O aq PhCH - CN org Na + int + Q + X - org PhCH - CN org Q + org + Na + X - aq PhCH - CN org Q + org + R-Xorg R Ph CN org + Q + X - org For a general review and applications see: Pure Appl. Chem. 2000, 72, 1399 and refs therein. N + OMe PMB Br - TMSCF 3 (1.2 equiv) KF (s) (1.5 quiv) Ph 3 SnF (0.3 equiv) DCM, rt, 24h 76% N OMe CF 3 PMB CAN (2.2 equiv) MeOH-H2O 4:1 90% N OMe CF 3 J. Org. Chem. 2007, 72, 5574 Andrzej Daniewski - Institute of Organic Chemistry, Polish Academy of Sciences - Hoffman-La Roche, NJ - 89 publications (Scifinder) - major research areas: synthesis of cardiotonic steroids, vitamin D, bioactive sesquiterpenes. Cl OMe O O O Me O O Me Cl O MeO O O Me OAc O N 2 MeO B 3 MeO Me O OH AcO O Me O OAc AcO AcO H MeO + Me OH HO HO H MeO O Me OH O H MeO O H Me H H MeO O H TsOAc Ac 2 O, 70% NaOH, MeOH BF 3 •Et 2 O acetone, then H 2 O 75% J. Org. Chem. 1975, 40, 3124, 3135 KOH, MeOH 80% 1. conc HCl 2. Ac 2 O, AcOH, 85% 3. chiral resolution 4. SOCl 2 5. CH 2 N 2 , 87% MeO O O O Me Me O MeO HBr, AcOH 14-dehydroequilenin O Me MeO O Me O MeO estrone 1. TiCl 4 2. Zn, 85% HClO 4 HBr Tet. Lett. 1982, 23, 2411 Organic Chemistry from the Eastern Bloc Baran Lab GM 08/13/2011 Florina Voica O Me O O Me i-Bu 2 AlO H O Me O H Br Me OH H O Me H OH Me H O Me OH Me HO tBuCu, DIBAL HMPA 57% 1. PDC, 65% 2. Wittig, 92% 3. LAH, 87% J. Org. Chem. 1988, 53, 5534 Br 2 Me O O Me O O H OH OTBS TBSO O H Me O H HO OAc H H OAc O Me O H H OAc OAc H H OAc Me OAc HO H H OAc Me OH H H Me O H OH tBuCu, DIBAL 70% 7 steps 1. mCPBA 2. Martin rgnt 90% 1. LAH 2. Ac 2 O 3. Martin rgnt 90% (3 steps) 1. N 2 H 4 , H 2 O 2 2. SeO 2 60% 1. Martin rgnt 2. KOH O Et Me O compactin Tet. Lett. 1990, 31, 5599 Prof. Janusz Jurczak - Ph.D, Institute of Organic Chemistry, Univ of Warsaw, 1970 - Post-doc, V. Prelog, ETH Zurich, 1971-1972 - Habilitation, Institute of Organic Chemistry, Univ of Warsaw, 1979 - Professor, Dept of Chemistry, Univ of Warsaw, 1991 - 457 publications (Scifinder) - major research areas: sugar chemistry, high-pressure rxns (Polish specialty), supramolecular chemistry (criptands). The case for high pressure DA reaction : - negative volume of activation (i.e. the volume occupied by the transition state is smaller than that of the reactants) - high pressure effects on the DA rxn: i) acceleration of the rxn ii) modification of regio- and diastereoselectivity iii) changes in chemical equilibria - equation describing rate dependency: δ ln k / δP = - δV / RT (k - rxn rate, P - pressure, V - transitions state volume, T - temp) - high pressure ~ 12-25 kbar - commonly used technique in industry and academic labs - cases when high pressure does the job: hindered dienes/dienophiles, LA/temp sensitive substrates, whenever you might want different product distribution. Synthesis 1979, 41; Chem. Commun. 1983, 540; Synthesis 1985, 928. OMe C 5 H 11 O + O OMe C 5 H 11 O O C 5 H 11 15-20kbar 50-65 °C, Et 2 O 28% 1. MoO 3 , 30%H 2 O 2 2. Ac 2 O, pyr 3. 10% Pd/C 24% overall J. Org. Chem. 1981, 46, 2230 OMe + H O Me NBocBzl O Me OMe NBocBzl H O Me OMe NBocBzl H 1. 15 kbar, 2% Eu(fod) 3 50 °C, Et 2 O 2. PPTS, rt, MeOH 80%, dr 16:1 major + J. Org. Chem. 1989, 54, 3759 purpurosamine B Organic Chemistry from the Eastern Bloc Baran Lab GM 08/13/2011 Florina Voica Prof. Marek Chmielewski - Institute of Organic Chemistry, Polish Academy of Sciences, Warsaw - 298 publications (Scifinder) - major research areas: sugar chemistry, β-lactam containing natural products, high pressure reactions, asymmetric reactions. O TMSO N • O + 1 equiv 3 equiv 1. CDCl 3 , rt, 1 atm, 6h, 42% 2. steps OTMS CCl 3 O O HO OH NBn N O Bn O OH HO J. Org. Chem. 1986, 51, 2395 Tet. Lett. 1987, 28, 3035 N + - O BnO F O O + N O O O OBn F CuI (0.1 equiv), TMG (2 equiv), ACN, 44% N O O OBn F N O OBn F OH F J. Org. Chem. 2011 ASAP Ezetimibe O Prof. Bogdan Marciniec - born 1941 - Ph. D, 1970, Adam Mickiewicz Univ, Poznan - Postdoc, 1971-1972, Kansas Univ - Habilitation, 1975, Adam Mickiewicz Univ, Poznan - Professor, 1986, Adam Mickiewicz Univ, Poznan - 298 publications (Scifinder) - major research areas: organosilicon chemistry , catalysis, macromolecular organosilicon structures. General reaction mechanism for the sylilative coupling of olefins with vinyl silanes: SiR 3 M H H SiR 3 H H M SiR 3 M H R 1 M R 1 H SiR 3 H H M H H R 1 H SiR 3 + SiR 3 R 1 R SiR 3 M = Ru, Rh, Co R = alkyl, aryl, alkoxy R 1 = alkyl, pheyl, OR, SiR 3 , -pyrrolidinone, carbazole Acc. Chem. Res. 2007, 40, 943 O O Si Si RuHClCO(PPh 3 ) 3 (1 mol%) 80 °C, 1h 85% Si O O Si Si O Si Si O Si TMSO + Si(OEt) 3 TMSO Si(OEt) 3 92% H 2 O/HCl 88% RuHCl(CO)(PCy3) (1 mol%) PhMe, 110 °C J. Org. Chem. 2005, 70, 370 Angew. Chem. Int. Ed. 2006, 45, 8180 Organic Chemistry from the Eastern Bloc Baran Lab GM 08/13/2011 Florina Voica Other accomplished polish chemists: -Prof. Tadeusz Jagodzinki - Technical Univ. of Szczecin - main research areas: synthesis and reactivity of thioamide derivatives of benzene and 5-membered heterocyles (Chem. Rev. 2003, 103, 197) - Prof. Maria Rozwadowska - Adam Michiewicz Univ, Poznan - main research areas: synthesis of isoquinoline alkaloids, chiral amines and sulfoxides. (Chem. Rev. 2004, 104, 3341) - Prof. Karol Grela - Institute of Organic Chemistry, Polish Academy of Sciences - main research areas: olefin metathesis. Main research centers: Univ of Ljublijana (first chem PhD 1920) National Institute of Chemistry, Ljubljiana Founding fathers: Fritz Pregl (1869-1930) - quantitative organic microanalysis Miha Tisler (1926-2001) - hetrocyclic chemistry Prof. Marko Zupan - born - Ph. D. 1974, Faculty of Chemistry and Chemical Technology, University of Ljubljana - Associate Professor, 1982-1987, University of Ljubljana - Professor, 1987-, University of Ljubljana - 233 publications (Scifinder) - main research areas: chemistry of halosubstituted organic molecules, fluorination of organic molecules ( Sarlah says... " [M. Zupan] was the first guy who started using XeF 2 in organic synthesis") Electrophilic fluorination with XeF 2 , CeSO 4 F F 3 C Br 1. Mg, Et 2 O 2. CS 2 3. XeF 2 F 3 C CF 3 77% Tet. Lett. 1990, 31, 3357 F F F XeF 2 105 °C, 2.5h 28% 42% 30% + + Bull. Chem. Soc. Jpn. 1986, 59, 1659 XeF 2 not an ideal fluorinating reagent... - no regioselectivity for aromatic substrates - olefin/aromatic ring substitution very important for reactivity... - strong oxidant, minimal FG tolerance - it usually requires an acid catalyst for activation - product distribution very sensitive to rxn conditions Ph Me O CsSO 4 F (1.1 equiv), ACN rt, 1.5 h 84% Ph F Me J. Org. Chem. 1992, 57, 5334 N N N F OSO 2 F + CsSO 4 F (2 equiv), rt cyclohexane 70% 30% Tet. Lett. 1990, 31, 775 N N Me Me O O CsSO 4 F (1.3 equiv) MeOH, 40 ° C F N N Me Me O O F F OMe 72% Tetrahedron 1990, 46, 3093 Electrophilic fluorination with N-F reagents (Selectfluor, Accufluor) N + N + Cl F Selectfluor N + N + F (BF 4 - ) 2 Accufluor O O Me Selectfluor solvent free 87% O O Me F Me O HO Me O O F Selectfluor (1.05 equiv) H 2 O, 60 °C 74% OEt OEt F Selectfluor solvent free 61% Tet. Lett. 2007, 48, 2671 Org. Lett. 2004, 6, 4973 Accufluor (1.1 equiv) ACN, 70 °C NHAc F F NHAc + 1 : 3 74% Chem. Commun. 1996, 2247 (BF 4 - ) 2 Organic Chemistry from the Eastern Bloc Baran Lab GM 08/13/2011 Florina Voica Main research centers: National Academy of Sciences, Kiev Kiev Polytechnic Institute Karkow National Univ Prof. Andrey A Fokin - Dept. of Organic Chemistry, Kiev Polytechnic Institute - 104 publications (Scifinder) - major research areas: nanodiamonds, cage structures, alkane functionalization, computational chemistry of radicals and radical cations. Br 50% NaOH/CBr 4 DCM, Et 3 BnNCl, 40 °C 37% 50% NaOH/CBr 4 DCM, Et 3 BnNCl, 40 °C 44% I NaOH, CHI 3 , rt, 24h 92% nPr Et Et I I NaOH, CHI 3 , rt, 24h 92% Br + 4 : 1 Angew. Chem. Int. Ed. 1998, 37, 1895; 1999, 38, 2786 O O S O NaH. DMSO 130 °C, 12h 96% p-TSA, DCM 96% Org. Lett. 2007, 9, 2541 O Me HO O H 2 SO 4 80 °C 65% MeMgBr 93% CF 3 CO 3 H TFA 80% Org. Lett. 2009, 11, 3068 Main research centers: National Academy of Sciences of Belarus Belorussian State Univ Founding fathers: too close to Russia, difficult to define.. Prof. Oleg Kulinkovich - born 1948 in Estonia - Ph. D, 1975, Belorussian State Univ, Minsk (prof. Tishchenko) - Professor, 1987, Belorussian State Univ, Minsk - 174 publications (Scifinder) - major research areas: development of cat and noncatalytic methods based on transformations of strained organic and organometallic compounds Kulinkovich reaction: R CO 2 Me R OH 1. EtMgBr (2 equiv) Ti(OiPr) 4 (5-10 mol%) Et 2 O, rt, 1h 2. 5% aq H 2 SO 4 , 5 °C 76-95% Synthesis, 1989, 234 Chem. Rev. 2003, 103, 2597 OH 8 OH 8 HO C 17 H 35 OH Me C 17 H 35 8 Me C 17 H 35 7 Me C 17 H 35 7 Me Me O 1. ethyl stearate (1 equiv) Ti(OiPr) 4 (1 equiv) C 6 H 10 MgBr (6 quiv) 2. H + , H 2 O N 2 H 4 , KOH, 190 °C 56% 1. P, I 2 150 °C 2. KOtBu, DMSO 1. MeCO 2 Et (1.4 equiv) Ti(OiPr) 4 (1.4 equiv) C 6 H 10 MgBr (7.1 equiv) 2. H + , H 2 O, 64% 3, 11 - dimethylnonacosan-2-one 3. KOH, THF, 67% Tet. Lett. 1998, 39, 1823 Me OH Me OH 2 1. Ti(OiPr) 5 (0.5 equiv) iPrMgBr (2 equiv), Et 2 O, rt 2. H + , H 2 O 72% Synlett 2003, 967 For more on red coupling, see Ian Young GM C 5 H 12 Organic Chemistry from the Eastern Bloc Baran Lab GM 08/13/2011 Florina Voica σ H complex vit D 3 metabolite Organic Chemistry from the Eastern Bloc Baran Lab GM 08/13/2011 Florina Voica The goal of this presentation is to offer a detailed perspective on the state of art in organic chemistry research in the major academic centers in former Eastern Bloc countries (Poland, Czech Republic, Slovakia, Hungary, Slovenia, Croatia, Serbia, Macedonia, Albania, Bulgaria, Romania, Moldova, Ukraine, Belarus, Lithuania, Latvia, Estonia). The analysis for each individual country consists in identifying the researchers who have made significant contributions to the field. Historic context: - The Eastern Bloc refers to the region in Europe which entered under Soviet influence after WWII (Yalta conferene, 1945); - These were communist countries, either directly reporting to Moscow, or having more "independent" communist regimes; - Under the strict, totalitarian policies, the economic development was "extensive rather than intensive", with chracteristic shortages of goods and minimal innovation; - After the fall of USSR (1989-1991), these countries adopted the free market economic model (and democratic governments), but in most cases the '90s remain a period of slow development (transition period/lost generation); - Nov 1993, The Maastricht Treaty established The European Union; - WIth the exception of Albania, Serbia, Montenegro, Croatia and Russia, all former communist countries are now part of the EU; General aspects: The scientist in society: During the almost half a century of soviet cultural influence, science and technology served an important part of national politics and identity. However, significant efforts were focused on pure science and theoretical research, with little practical applications or economic impact. The educational system "In spite of all the apparent shortcomings and faults, the Russian secondary schools seem to prepare the students relatively well for life and for higher education, especially in the sciences and mathematics. The intensity of the work and the student's motivation to succeed is a big factor. Admission to higher education is a crucial, life-long decision and it is made while the student in still in the secondary school." "In general, the Soviet Educators in higher educational institutions receive and work with a better motivated and selected student than their American counterparts. However, the rigid requirements and screenings have an already built-in weakness due to over-specialization." "The earned Doctor degree is supposed to be based on research work containing a theoretical utilization and the solution of a major scientific problem representing a considerable contribution to science and to practical work. It should have a serious impact". J. Chem. Educ. 1971, 48, 60; 1973, 50, 520. The pharmaceutical industry: - generic drugs account for more than half of the total market (in value) and almost 3/4 in volume (july 2011); - major generic companies: KrKa (Slovenia), Gedeon Richter (Hungary), PolPharma (Poland), Zentiva (Romania), Pharmstandard (Russia). - highest sales in cardiovascular market, followed by alimentary canal and metabolic disorders; - importantly, the health care system is run by the government, so obviously there is little impetus for significant R&D programs. http://blog.pharmexec.com/2009/09/02/pharma-industry-booming-in-eastern-europe/ http://www.espicom.com/prodcat2.nsf/Product_ID_Lookup/00000396?OpenDocument https://www.mckinseyquarterly.com/Pharmas_generics_opportunity_in_Central_and_Eastern_Europe_2186# Chemistry Nobel Prize winners - awarded from 1945-2011; chemists who were residents in their countries of birth when they received the award: Nikolay Semyonov (Russia), 1956 - for work on the mechanism of chain reactions; Jaroslav Heyrousky (Czech Republic), 1959 - for developing the polarographic method of analysis; Vladimir Prelog (Croatia), 1975 - for research into the stereochemistry of molecules and reactions; - awarded from 1945-2011; eastern european born chemists who led their research in other countries: Ilya Prigogine (born Russia), 1977 - for his work on dissipative structures, complex systems, and irreversibility; Roald Hoffmann (born Ukraine), 1981 - for the Woodward-Hoffman rule; Aaron Klug (born Lithuania), 1982 - for his development of crystallographic electron microscopy and his structural elucidation of biologically important nucleic acid-protein complexes George Olah (born Hungary), 1994 - for work on carbocations generated with superacids; Avram Hershko (born Hungary), 2004 - for the discovery of ubiquitin-mediated protein degradation. "The earned Doctor degree is not a degree in the American sense, but a sign of recongition which could be compared to our post-doctoral experience. Too many Russians remain in one place to work and study under the same man in one field. This creates inbreeding and an educational system that lacks imagination and produces research contributions not up to the level of effort exerted and manpower used" Prof. Branko Stanovnik (Ph.D, 1964) - 583 publications - heterocyclic chemistry Founding fathers: I.K.Matsurevich (active in '30-'40) - nat prod synthesis V.P.Yavorskii - chemical transformations of aliphatic compounds V.G.Shaposhnikov - aromatic and heterocyclic chemistry Czech Republic Main research centers: Prague Institute of Chemical Technology; Institute of Organic Chemistryvand Biochemistry (Prague) Active researchers: Prof. Srogl Jiri (currently at Emory Univ) - bioactive inspired metal coupling rxns (Ni and Pd catalyzed coupling of thio-esters with boronic acids) Prof. Petr Beier (currently at Univ. of Southern California) - organic sulfur, phosphorus, silicon and fluorine chemistry. Slovakia Main research centers: Slovak Academy of Sciences; Institute of Organic Chemistry; Slovak Technical Univ Main areas of research: sugars chemistry... Estonia Main research centers: Tallin Univ of Technology Active researchers: Prof. Margus Lopp - asymmetric synthesis (asymmetric Bayer Villiger ...) Latvia Main research centers: Latvian Institute of Organic Synthesis (Riga), Latvian Academy of Sciences, Riga Technical Institute Active researchers: Prof. Edgars Suna (32 publications) - asymmetric reductions Prof. E. Lukevics (1936-2009) - chemistry of organosulfur, silicon, germaniun compounds Lithuania Main research centers: Vilnius Univ Active researchers: undetectable... Romania Main research centers: Bucharest Univ Polytechnic Institute (Bucharest) Technical Univ, Cluj-Napoca Founding fathers: Prof. Costin Nenitzescu ( 1902-1970) (Friedel-Crafts reaction, first to synthesize cyclobutadiene, oxidations of aliphatics with chromiun oxidants, Nenitzescu indole synthesis) Prof. Alexandru Balaban (born 1931) (currently at UT, Austin) (theoy of aromaticity, pioneer of the chemical graph theory) Active researchers: not so much in organic chemistry... more in inorganic and analitical Bulgaria Main reseach centers: Bulgarian Academy of Sciences, Institute of Organic Chemistry Plovdiv Univ Active researchers: Prof. Vladimir Dimitrov - organometallic chemistry, sythesis of asymmetric ligands Left uncovered.... Hungary(!!), Croatia(!), Serbia(!), Macedonia, Bosnia, Moldova, Albania, Russia(!!!!) OH