Preparation of Compounds Labeled With Tritium and Carbon-14
, by Voges, Rolf; Heys, J. Richard; Moenius, Thomas
- ISBN: 9780470516072 | 0470516070
- Cover: Hardcover
- Copyright: 5/18/2009
Compounds tagged with carbon14 and tritium are critical tools in research in biomedical sciences, discovery, and development of pharmaceuticals and agrochemicals, and investigations into the nature of chemical reactions and the ways living organisms incorporate and modify biological components. A must for scientists, technicians, synthetic organic chemists, and radiochemists, Preparation of Compounds Labelled with Tritium and Carbon14 for Application in Life Sciences is a comprehensive, authoritative, and up-to-date guide to the specialist strategies and tactics used by chemists to prepare compounds tagged with the radioactive atoms carbon14 and tritium.
Rolf Voges studied chemistry at the Universities of Marburg and Freiburg, where he received his Ph.D. in organic chemistry on investigations into steric isotope effects, for which he received the Go¨deke Award. After postdoctoral research on stereoselective syntheses he joined the isotope group of Sandoz Pharma AG (now Novartis AG) being involved for thirty years in organic radiochemical synthesis as Head of the Isotope Laboratories and then Head of Isotope Section. He is author or coauthor of about 40 publications, one patent, and coeditor of two previous conference proceeding volumes in the field, co-organizer of two international symposia on the synthesis and application of isotopically labeled compounds, founder and co-organizer of eleven Bad Soden meetings of the Central European Division of the International Isotope Society (CED-IIS), and co-editor of the proceedings. For three years he held a leadership position in the IIS, serving as its 2001 president. In recognition of his scientific achievements and his service to the isotope society he received the IIS-CED Award in 1995 and in 2003 the IISAward. He is now retired and lives in southwestern Germany, near the Swiss and French borders.
Richard Heys received his Ph.D. in organic chemistry from Stanford University in 1976 and conducted postdoctoral research in the chemistry department at Yale; both involved the synthesis of radiolabeled compounds and their use in elucidation of biosynthetic pathways. His subsequent 29-year career in organic radiochemical synthesis both in the laboratory and as a manager took him to the Radiochemistry Department of Midwest Research Institute (now part of Aptuit, Inc.), Smith Kline & French Laboratories/SmithKline Beecham Pharmaceuticals (now GlaxoSmithKline) and AstraZeneca Pharmaceuticals. Author or coauthor of over 85 publications, 8 patents and a previous conference proceedings volume in the field, organizer of an international symposium on the synthesis of isotopically labeled compound and holder of leadership positions (including president and CFO) in the International Isotope Society for 9 years, he is retired and lives in northwestern Connecticut.
Thomas Moenius received his Ph.D. in organic chemistry from the University of Erlangen-Nu¨rnberg in 1986. He is a member of the isotope group of Novartis Pharma AG, working in the field of carbon-14 and tritium labeling. Since 2007 he is also European Editor for Journal for Labelled Compounds and Radiopharmaceuticals.
| Preface | p. xi |
| Glossary | p. xiii |
| Author Biographies | p. xvii |
| Introduction | p. 1 |
| Physical Properties of Tritium and Carbon-14 | p. 3 |
| Purification | p. 5 |
| Analysis | p. 6 |
| Chemical Identity | p. 6 |
| Chemical (and Enantiomeric) Purity | p. 7 |
| Radiochemical (and Radionuclidic) Purity | p. 8 |
| Specific Activity | p. 9 |
| Position of Label | p. 10 |
| Stability and Storage of Compounds Labeled with Tritium or Carbon-14 | p. 11 |
| Specialist Techniques and Equipment | p. 15 |
| References | p. 21 |
| Strategies for Target Preparation | p. 25 |
| Formulating Target Specifications | p. 26 |
| Planning Radiotracer Preparations | p. 31 |
| The Construction Strategy | p. 31 |
| Reconstitution Strategies | p. 32 |
| The Derivatization Strategy | p. 34 |
| Selection of an Appropriate Strategy | p. 34 |
| Case Studies of Strategy Development | p. 36 |
| References | p. 44 |
| Preparation of Tritium-Labeled Compounds by Isotope Exchange Reactions | p. 47 |
| Homogeneous Acid-or Base-Catalyzed Exchange | p. 49 |
| Exchange without Added Acid or Base | p. 49 |
| Exchange under Acidic Conditions | p. 51 |
| Exchange under Basic Conditions | p. 56 |
| Heterogeneous Catalysis with Tritium in Solvent | p. 60 |
| Metals | p. 61 |
| Other Catalysts | p. 65 |
| Heterogeneous Catalysis in Solution with Tritium Gas | p. 66 |
| Metal Catalysts with Nonreducible Substrates in Aqueous Solution | p. 67 |
| Metal Catalysts with Nonreducible Substrates in Organic Solvents | p. 68 |
| Other Catalysts | p. 69 |
| Metal Catalysts with Reducible Substrates | p. 70 |
| Homogeneous Catalysis in Solution with Tritiated Water | p. 71 |
| Exchange Catalyzed by Metal Salts | p. 71 |
| Exchange Catalyzed by Organoruthenium Complexes | p. 73 |
| Exchange Catalyzed by Iridium Dionates | p. 74 |
| Exchange Catalyzed by Iridium Cyclopentadienides | p. 76 |
| Homogeneous Catalysis with Tritium Gas | p. 77 |
| Iridium Phosphines | p. 77 |
| Iridium Dionate Complexes | p. 90 |
| Iridium Cyclopentadienide Complexes | p. 91 |
| Solvent-Free Catalytic Exchange | p. 93 |
| High-Temperature Solid-State Catalytic Isotope Exchange | p. 93 |
| Thermal Tritium Atom Bombardment | p. 96 |
| Other Radiation-Induced Labeling Methods | p. 97 |
| References | p. 98 |
| Preparation of Tritium-Labeled Compounds by Chemical Synthesis | p. 109 |
| Catalytic Tritiations | p. 110 |
| Tritiation of Carbon-Carbon Multiple Bonds | p. 111 |
| Tritiation of Carbon-Heteroatom Multiple Bonds | p. 125 |
| Homogeneously Catalyzed Reactions | p. 126 |
| Catalytic Tritiolyses | p. 132 |
| Tritiodehalogenations | p. 133 |
| Tritiolyses of Benzylic N- and O-Functions | p. 144 |
| Tritiodesulfurizations | p. 145 |
| Tritide Reductions | p. 146 |
| Sodium Borotritide (NaB3H4) | p. 148 |
| Sodium Cyanoborotritide (NaB3H3CN) | p. 157 |
| Sodium/Tetramethylammonium Triacetoxyborotritide [Na/NMe4B3H(OAc)3] | p. 159 |
| Lithium Tritide (Li3H) | p. 160 |
| Lithium Borotritide (LiB3H4) | p. 161 |
| Lithium Triethylborotritide (LiEt3B3H, Li-Super-Tritide) | p. 163 |
| Lithium Tri-sec-Butylborotritide [Li(sec-Bu3)B3H, Li T-Selectride] | p. 165 |
| Lithium [3H2]Boratabicyclo[3.3.1]nonane | p. 166 |
| Tritiated Borane (THF-Complex) (B23H6; B3H3.THF) | p. 167 |
| Tritiated Alkylboranes | p. 169 |
| Lithium Aluminum Tritide (LiAl3H4) | p. 170 |
| Tri-n-Butyltin Tritide (n-Bu3Sn3H) | p. 172 |
| Tritiated Schwartz's Reagent (ZrCp2Cl3H) | p. 176 |
| Tritiated Triethylsilane and Trihexylsilane | p. 177 |
| Small Tritiated Building Blocks | p. 178 |
| Tritiated Water (3H2O; 3HHO) | p. 179 |
| Tritiated Diimide (3HN = N3H) | p. 182 |
| Tritiated Methyl Iodide (C3H3l; C3HH2I) | p. 183 |
| Tritiated Diiodomethane (C3HHI2) | p. 190 |
| Tritiated Formaldehyde (3HCHO, 3HC3HO) | p. 191 |
| Dimethyl [3H]formamide (3HCONMe2), Acetic [3H]Formic Anhydride (3HCOOCOMe) | p. 192 |
| Tritiated Diazomethane (C3HHN2) | p. 193 |
| N-Tritioacetoxyphthalimide | p. 194 |
| N-Succinimidyl [2,3-3H]Propionate ([3H]NSP) | p. 195 |
| References | p. 195 |
| Barium [14C]Carbonate and the Preparation of Carbon-14-Labeled Compounds via One-Carbon Building Blocks of the [14C]Carbon Dioxide Tree | p. 211 |
| [14C]Carbon Dioxide (14CO2) | p. 212 |
| [14C]Carboxylations of Organometallic Compounds | p. 212 |
| Manipulations of [14C]Carboxylation Products | p. 218 |
| N-[14C]Acyl Building Blocks | p. 219 |
| Preparation of Other Building Blocks from [14C]Carbon Dioxide | p. 221 |
| [14C]Carbon Monoxide (14CO) | p. 222 |
| [14C]Phosgene | p. 229 |
| [14C]Formic Acid (H14COOH) | p. 233 |
| [14C]Formaldehyde (H14CHO) | p. 240 |
| Carbanion-Mediated Hydroxy[14C]methylation and [14C]Methylenenation | p. 242 |
| Acid-Catalyzed Hydroxy[14C]methylations | p. 246 |
| Amino[14C]methylation | p. 248 |
| Reductive Methylations | p. 254 |
| Polycondensations | p. 255 |
| Thio[14C]methylations | p. 256 |
| [14C]Methyl Iodide (14CH3I) | p. 256 |
| [14C]Methyl Iodide as an Electrophilic One-[14C]Carbon Building Block | p. 257 |
| [14C]Methyl Iodide as a Source of Nucleophilic [14C]Methyl and [14C]Methylene Building Blocks | p. 262 |
| Further Building Blocks Derived from [14C]Methyl Iodide | p. 268 |
| [14C]Nitromethane (14CH3NO2) | p. 270 |
| References | p. 277 |
| Preparation of Carbon-14-Labeled Compounds via Multi-Carbon Building Blocks of the [14C]Carbon Dioxide Tree | p. 287 |
| [14C]Acetic Acid and Its Derivatives | p. 287 |
| [14C]Acetic Acid | p. 287 |
| [14C]Acetyl Chloride | p. 289 |
| [14C]Acetic Anhydride | p. 298 |
| [14C]Acetic Acid Alkyl/Aryl Esters | p. 301 |
| Halo[14C]acetates | p. 307 |
| Reaction at the Carboxyl Group | p. 309 |
| Reactions at the Methylene Group | p. 312 |
| Reactions at the Halogen Atom | p. 314 |
| [14C]Acetone | p. 337 |
| Reaction at the Carbonyl Group | p. 338 |
| Reaction at the Methyl Group | p. 343 |
| Alkyl [14C]Acetoacetate | p. 346 |
| Alkylation Reactions | p. 348 |
| Acylation Reactions | p. 351 |
| Aldol Reactions | p. 352 |
| Knoevenagel-Michael Reactions | p. 353 |
| Reactions at the Functional Groups | p. 356 |
| [14C]Malonates | p. 357 |
| Reactions at the Methylene Group | p. 359 |
| Reactions at the Carboxyl Functions | p. 374 |
| References | p. 381 |
| Preparation of Carbon-14-Labeled Compounds via the [14C]Cyanide Tree | p. 393 |
| Metal [14C] Cyanides | p. 393 |
| Preparation | p. 393 |
| Introduction of [14C]Cyanide into Organic Substrates | p. 394 |
| Synthetic Transformations of Organic [14C]Nitriles | p. 399 |
| Preparation of Other Building Blocks from [14C]Cyanide | p. 411 |
| Trimethylsilyl[14C]Cyanide (TMS14CN) | p. 412 |
| [14C]Cyanogen Bromide (Br14CN) | p. 413 |
| Alkali Metal [14C]Cyanates (M14CNO; M = Na, K) | p. 415 |
| Alkali Metal Thio[14C]cyanate (M14CNS; M = Na, K) | p. 417 |
| Triethy [14C]Orthoformate [H14C(OEt)3] | p. 419 |
| [14C]Cyanoacetic Acid [14CNCH2COOH] | p. 420 |
| [14C]Diazomethane (14CH2N2) | p. 431 |
| References | p. 433 |
| Preparation of Carbon-14-Labeled Compounds via the [14C2]Acetylene Tree | p. 441 |
| [14C2]Acetylene (H14C = 14CH) | p. 441 |
| [14C2]Acetaldehyde (14CH314CHO) | p. 445 |
| [1,2-14C2]Acetic Acid (14CH314COOH) | p. 446 |
| 2-[2,3-14C2]Propyne-1-ol ([2,3-14C2]Propargyl Alcohol) and 2-[2,3-14C2]Butyne-1,4-diol | p. 447 |
| Methyl [2,3-14C2]Propiolate (H14C$$14CCOOMe) and Dimethyl [2,3-14C2]Acetylenedicarboxylate (HOOC14C$$14CCOOH) | p. 447 |
| 1,2-[14C2]Dibromoethane (Br14CH214CH2Br) | p. 448 |
| [14C2]Ethylene Oxide | p. 448 |
| [14Cn]Benzene and the Synthesis of Ring-Labeled Aromatic Compounds | p. 448 |
| Nitrobenzene Branch | p. 451 |
| Phenol Branch | p. 454 |
| Bromobenzene Branch | p. 456 |
| Iodobenzene Branch | p. 457 |
| Benzoic Acid Branch | p. 458 |
| Alkyl Phenyl Ketone Branch | p. 459 |
| Sulfonylbenzene Branch | p. 459 |
| References | p. 460 |
| Preparation of Carbon-14-Labeled Compounds via the [14C]Cyanamide Tree | p. 465 |
| [14C]Cyanamide (H2N14C$$N) | p. 465 |
| [14C]Guanidine (H2N14C(=NH)NH2) | p. 467 |
| [14C]Urea, H2N14CONH2 | p. 468 |
| [14C]Thiourea, H2N14CSNH2 | p. 472 |
| References | p. 477 |
| Reconstitution Strategies | p. 479 |
| Replacement Strategies | p. 479 |
| 1H/3H Replacement Strategies | p. 479 |
| 12C/14C Replacement Strategies | p. 485 |
| Disconnection-Reconnection Strategies | p. 488 |
| Dealkylation-Re[3H/14C]alkylation Procedures | p. 488 |
| CO2/14CO2 Replacement Strategies | p. 492 |
| CO/14CO Replacement Strategy | p. 501 |
| Oxidative Cleavage of C=C Bonds in the Reconstitution Approach | p. 502 |
| References | p. 517 |
| Preparation of Enantiomerically Pure Compounds Labeled with Isotopes of Hydrogen and Carbon | p. 523 |
| Resolution of Racemates | p. 524 |
| Enantioselective Synthetic Methods | p. 529 |
| Hydrogenation/Tritiation of Labeled/Unlabeled ¿2,3-Amino Acid Derivatives | p. 530 |
| Reduction of Labeled Prochiral Carbonyl Compounds and Oximes | p. 535 |
| Enantioselective Oxidation of Olefins and Allylic Alcohols | p. 541 |
| Diastereoselective Synthetic Procedures | p. 546 |
| ¿-Alkylation of Chiral Imide Enolates | p. 551 |
| Aldol Reactions of Chiral Imides and Ester Enolates | p. 558 |
| 1,4-Additions of Chiral Imide Enolates to Michael Acceptors | p. 564 |
| ¿-Amination of Chiral Imide Enolates | p. 566 |
| ¿-Hydroxylation of Chiral Imide Enolates | p. 571 |
| ¿-Alkylation of Chiral Glycinates | p. 571 |
| Aldol Reactions of Chiral Glycinates | p. 583 |
| Aldol Reactions of Chiral Glycolates | p. 586 |
| Aldol Reactions of Chiral Haloacetates | p. 586 |
| Reactions on Chiral ¿,ß-Unsaturated Imides and Esters | p. 591 |
| References | p. 596 |
| Biotransformations in the Preparation of Compounds Labeled with Carbon and Hydrogen Isotopes | p. 607 |
| Applications of Isolated Enzymes | p. 608 |
| Optical Resoultions via Derivatives | p. 608 |
| Synthesis of Isotropically Labeled, Enantiomerically Pure Compounds | p. 612 |
| Conjugation Reactions | p. 618 |
| Application of Cell-Containing Systems | p. 618 |
| Transformations of Functional Groups | p. 619 |
| Fermentative Synthesis of Structurally Complex Molecules by Incorporation of Labeled Precursors | p. 621 |
| Specific Requirements for Fermentations Using Isotopically Labeled Compounds | p. 623 |
| Biocatalyzed Synthesis of Key Intermediates for Reconstitution Approaches | p. 630 |
| Oxidation-Reduction Approach | p. 631 |
| Dealkylation-Realkylation Approach | p. 632 |
| References | p. 634 |
| Index | p. 639 |
| Table of Contents provided by Ingram. All Rights Reserved. |
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