“chemical engineering”

Course content:

• 
  The physical and chemical properties and biological activities of the substances. The interaction between the drugs’ substances and the receptor. The biological membranes. The transportation of the drugs to the point of the biological action. The elimination of the drugs from the organism. The molecular graphic in the contruction of the drugs. The metabolism of the drugs.
  

Literature:

1. 
   A.Kleemann, J.Engel. Pharmaceutische Wirkkstoffe. Thieme Verl. Stuttgart, New-York, 1987.
   
2. 
   S.Pfeifer, P.Pflegel, H.-H.Borschert. Grundlangen der Biopharmazie. Lehrbuch. Berlin, Volk und Gesundheit, 1984.
   
3. 
   Diversity of Interacting Receptors. Ed. L.G. Abood, A.Lajthe. New-York, Acad.Sci., 1995, 531 pp.
   
4. 
   V.Kluša, S.Svirskis. Signāla transdukcijas mehāmismi. LU.OSI. Rīga, 1998 (mācību līdzekļi).
   

Ready forms of the drugs

ĶOS 483

Assistant Professor Ilze Bārene

Course description: 2 Credit units; 32 hours (32 lectures)

Control forms: test

Course content:

• 
  The ready forms of drugs and their regulation. The medical substance and auxiliary materials. The drugstores and industrial ready forms. Asepsis and sterilization. The main directions of the production of the industrial ready forms. Auxiliary materials. The production of the pills, granules, capsules and sugared pills. The drugs for the injections. The unguents. The medical aerosols.
  

Literature:

1. 
   Технология лекарственных форм. Учебник в двух томах. Под ред. Т.С. Кондратьевой. Москва. Медицина. 1999. Т.1 – 496 с. Т.2. – 544 с.
   
2. 
   R. Voigt. Lehrbuch der pharmazeutischen Technologie. VCH, 1987, S.807.
   

3. И.А.Муравьев. Технология лекарств. Учебник. Москва. Медицина.

Chemistry and technology of medicinal substances

ĶOS 484
Professor Andris Strakovs

Course description: 3 Credit units; 48 hours (32 lectures, 16 laboratories)

Control forms: exam

Course content:

• 
  The predominate role of chemistry and technology of thin organic synthesis in chemistry and technology of medicinal substances. The general historical stages of development in chemistry and technology of medicinal chemistry. The general thesis, principles, achievements and unsoluted problems in modern medicinal chemistry. The classification of medicinal substances. General schemes of search of novel medicinal substances and organization of manufacture. The first biological tests (screening). Profound testing of biological activities, their reglamentation, clinical trials. Elaboration of manufactoral technology of active forms. Elaboration of finished forms of medicinal substances and their manufactural technology. The general classes of medicinal substances. Analgetic-antipyretic substances. Off prescription state medicines. Soporific and sedative medicines. Analeptic substances. Medicines with influence to transfer of impulse of Central Nervous System. Antihistamine substances. Anticancer substances. Antibiotics. Antivirus medicines. Vitamins and hormones. Search of novel medicinal substances and manufarcture in Latvia. Nowdays situation and perspective of search of novel medicines and manufacture in order countries.
  
• 
  Laboratories: Synthesis of drug substances (1)
  

Literature:

1. 
   Р.П.Евстигнеева. Тонкий органический синтез. Москва, Химия, 1991,184 с.
   
2. 
   В.Г.Беликов. Фармацевтическая химия. Москва, Высшая школа, 1985, 768 с.
   
3. 
   G. Vagner. Lehrbuch der pharmazeutischen Chemie. VEB-Verlag, Berlin, 1987, S 602.
   

Teсhnology of the pharmaceutic preparation

ĶOS 501

Professor Andris Strakovs

Course description: 4 Credit units; 64 hours (32 lectures, 32 laboratories)

Control forms: exam

Course content:

• 
  The individualities of the technology of the pharmaceutic preparations.
  
• 
  The standing order. The reactors. The materials and warm balances. The set of the apparatus, the pipelines. The contruction materials. The regulation of the production and the laboratories trial of the substances and the ready drugs’ forms. The determination of the stability and quality of the ready drugs’ forms. The industrial production of the pills and solutions for injections.
  

Literature:

1. 
   Технология лекарственных форм. Учебник в двух томах. Под ред. Т.С. Кондратьевой. Москва. Медицина. 1999. Т.1 – 496 с. Т.2. – 544 с.
   
2. 
   R. Voigt. Lehrbuch der pharmazeutischen Technologie. VCH, 1987, S.807.
   
3. 
   И.А.Муравьев. Технология лекарств. Учебник. Москва. Медицина.
   

Selected chapters of chemistry and technology of medicinal substances

ĶOS 505
Professor Andris Strakovs

Course description: 2 Credit units; 32 hours (16 lectures, 16 laboratories)

Control forms: exam

Course content:

• 
  Basic principles and particularities of screening of new medicaments.
  
• 
  Substances with impact on function of the heart and circulatory system
  
  • 
    cardiotonical medicaments: nitrites and nitrates, nitrogen heterocycles, oxygen
    
  • 
    heterocycles, -adrenoblocators, + adrenoblocators, calcium antagonists.
    
  • 
    antihypertensical medicaments, neurotropical drugs, peripheral vasodilatators, diuretics, inhibitors of reninangiotensin system.
    
  • 
    Antiatherosclerotical drugs.
    
  • 
    Medicaments of antithrombosis: heparine, 4-hydroxyqumarines and 1,3-indandiones, their synthesis, other anticoagulants, K vitamins for coagulation.
    
  • 
    Replacements of blood plasma .
    

Literature:

1. 
   Р.П.Евстигнеева. Тонкий органический синтез. Москва, Химия, 1991,184 с.
   
2. 
   В.Г.Беликов. Фармацевтическая химия. Москва, Высшая школа, 1985, 768 с.
   
3. 
   A.Kleemann, J.Engel. Pharmazeutische Wirkstoffe. 1982-1987. G.Thieme Verlag, Stuttgart, New York, 1987.
   

Selected chapters of organic synthesis

ĶOS 549

Associated Professor Māra Jure

Course description: 6Credit units; 96 hours (32 lectures, 64 laboratories)

Control forms: exam
Course content:

• 
  SOLVENTS IN organiC sYntHESIS Solvent and solute interaction. Solutions. Intermolecular interaction (hydrogen bonding, EPD/EPA interaction, etc.). Solvation. Micellar solvation. Classification of solvents (by chemical properties, physical properties, acidity/basicity, interaction between solvent and solute, multicomponent statistical analysis). Solvents as reaction media. Solvents for crystallisation and extraction. Toxicity of solvents.
  

• 
  ENOLATES AND ENAMINES
  

1. Methods of carbanionu generation, selection of base and solvent. Regio- and stereoselectivity of enolates formation, termodynamic and kinetic control. Alkylation of enolates. Generation and alkylation of dianions. Media effects in alkylation of enolates - solvents, metal ions, complexation agents.

• 
  ELEMENTORGANIC COMPOUNDS
  

1. Methods of synthesis of Li and Mg organic compounds - reduction of halogenides and sulfides, metallation, exchange reactions M’ - M, X - M. Li and Mg reagents in crystal form and in solutions (monomers, dimers, tetramers, heksamers; solvent effect). Commercially available Li reagents. Li organic derivatives as bases. Shapiro reaction.

2. Reactions of Li and Mg organic compounds with alkylation reagents. Reactions of Grignard reagents with carbonylcompounds and nitriles; minor products - reduction and enolisation of ketones, isomerization of unsaturated Grignard reagents, cyclic mechanisms; stereoselectivity. Reactions of Li organic derivatives with carbonylcompounds; stereoselectivity.

3. Organic compounds of II B group metals Zn and Cd. Synthesis. Physical and chemical properties of Zn organic compounds (use in synthesis of elementorganic compounds, reactions with carbonylcompounds, Reformatsky reaction, mixed aldol condensation, Lombardo reagent etc.). Organic derivatives of Cd in synthesis of ketones.

4. Organic compounds of Hg. Synthesis. Physical and chemical properties, toxicity. Oxymercuration. Ce organic compounds.

5. Organic compounds of Cu, their synthesis, physical and chemical properties. Organic compounds of Cu in S_N reactions; cleavage of epoxydes, conjugated addition to -unsaturated carbonylcompounds, tandem reactions, addition to alkynes (Normant reagent), dimerization reactions (Ullmann, Glaser, Eglinton, Cadiot-Chodkiewicz reactions).

6. Pd in organic synthesis. Formation of -complexes. S_N un A_N reactions of alkenes catalised by Pd (II) (Wacker reaction). Reactions of -allylcomplexes with nucleophiles. Reaction of oxidative addition products of Pd (0) to aryl- and alkenylhalides with alkenes, organometallic compounds (coupling), carbonylation.

7. Organic derivatives of transittion metals Ni, Rh, Fe, Co. Synthesis, physical and chemical properties. Compounds with  bonding. Usage of Ni organic derivatives in coupling reaction of halogenides. Rh and Co catalysts for hydroformylation reaction (Fischer-Tropsch reaction). Carbonylation. Ti catalysts in McMurry reaction. Sharpless assymetric epoxydation.

8. Organic compounds of Sn. Commercially available Sn organic compounds. Synthesis of stannanes. Reactions of alkenyl- and allylstannanes with electrophiles. Stannanes as source of carbanions in transition metals catalized reactions (Pd catalized crosscoupling with halogenides, acylhalides and vinyltriflates; carbonylation). Stannanes in free radical rections (additions to alkenes; allylation of halogenides and selesnides; cyclizaton; tandem cyclization; fragmentation and rearrangements).

9. Organic derivatives of B. Hydroboration of alkenes with borane, alkylboranes (regio- and stereochemistry). Sia₂BH, texylborane, 9-BBN, “Alpine-borane”®. Reactions of alkylboranes (syntheses of alchocoles, amines, halogenderivatives, alkanes; termal isomerization; carbonylation). Hydroboration of dienes and alkynes (boracycloalkanes in syntheses of cyclic ketones). Reduction of carboxylic acids with borohydrides and boranes.

10. Organic compounds of Si. Synthesis and commercially available reagents. Carbon-carbon bond formation using Si organic compounds: Peterson synthesis; Si stabilized carbanions; reactions of vinylsilanes, allylsilanes, silylethers of enols (silyloxyalkenes), silyloxybutadienes; fluoride aniona induced reactions. Fluoride aniona induced elimination and reduction reactions. Synthetic use of iodotrimethylsilane. Silylgroups as protective groups for alchocols.

11. Organic compounds of P (Michaelis-Arbusov reaction). Syntheses of alkenes and alkynes (Wittig reaction; Horner/Wadsworth-Emmons reaction). Interconversions of functional groups (hydroxylgroup exchange to halogen; synthesis of amides and esters; dehalogenation of arylhalides). Dezoxygenation reactions (reduction of N-oxides of amines; cyclization reactions with assistance of nitro- and nitrozogroups; dezoxygenation of sulfoxydes).

12. Organic compounds of S, Se, Te. Syntheses, toxicity, commercially available Se reagents. Elimination reactions of selenoxydes. Use of allylselenides (rearrangements of allylselenoxydes; synhteses of -hydroxyalkenes; Se-Li exchange reactions). C-Se bond hydrogenolysis (reductive alkylation of aldehydes and ketones; syntheses of heterocycles; oxxidation of alkenes to ketones). Oxydation with Se (IV) reagents. Use of SeO₂ in synthesis of -diketones, oxydation to allylposition. Pummerer and Swern oxydation.

• 
  PERICYCLIC REACTIONS
  

Molecular orbitals, symmetry elements, theory of frontal orbitals. Cycloaddition, electrocyclic reactions, sigmatropic rearrangements, heletropic, “ene” and group migration reactions. Simmetry allowed and simmetry forbidden reaction prediction rules: Woodward and Hoffmann rules, correlation diagrams, Huckel method.

• 
  RETROSYNTHETIC ANALYSIS
  
• 
  CONTEMPORARY ORGANIC SYNTHESIS
  

Reactions; new mechanisms; reagents; solvents; technique of synthesis - sonochemistry, electrochemistry, phase transfer catalysis, photochemistry etc.
Literature:

1. 
   F.A.Carey, R.J.Sundberg. Advanced Organic Chemistry. 3rd Ed. Part A. Structure and Mechanisms. 1990.
   
2. 
   F.A.Carey, R.J.Sundberg. Advanced Organic Chemistry. 3rd Ed. Part B. Reactions and Synthesis. 1990.
   
3. 
   T.H.Lowry, K. S.Richardson. Mechanism and theory in organic chemistry. 2nd ed. 1981.
   
4. 
   J.March. Advanced Organic Chemistry. Reactions, Mechanisms and Structure. 4th Ed. 1992.
   
5. 
   Íåéëàíä Î.ß. Îðãàíè÷åñêàÿ õèìèÿ. 1990.
   
6. 
   O.Neilands. Organiskā ķīmija. 1977.
   
7. 
   Èîôôå Á.Â. Ñîâðåìåííûå ìåòîäû îðãàíè÷åñêîãî ñèíòåçà. 1980.
   
8. 
   Rthb A.> Cfyl,thu H. Euke,ktyysq rehc jhufybxtcrjq [bvbb. V.> {bvbz> 1981.
   
9. 
   Ìàêè Ð., Ñìèò Ä. Ïóòåâîäèòåëü ïî îðãàíè÷åñêîìó ñèíòåçó. 1974.
   
10. 
    Ìàð÷ Äæ. Îðãàíè÷åñêàÿ õèìèÿ. Ò. 1. 1987.
    
11. 
    Ìàð÷ Äæ. Îðãàíè÷åñêàÿ õèìèÿ. Ò. 2. 1987.
    
12. 
    Ìàð÷ Äæ. Îðãàíè÷åñêàÿ õèìèÿ. Ò. 3. 1987.
    
13. 
    Ìàð÷ Äæ. Îðãàíè÷åñêàÿ õèìèÿ. Ò. 4. 1988.
    
14. 
    Ìàíäåëüøòàì Ò.Â. Ñòðàòåãèÿ è òàêòèêà îðãàíè÷åñêîãî ñèíòåçà. 1989.
    
15. 
    Òàíòàøåâà Ô.Ð. Ìåòîäû îðãàíè÷åñêîãî ñèíòåçà. 1988.
    
16. 
    M.E.Alonso. The Art of Problem Solving in Organic Chemistry. 1987.
    
17. 
    R.C.Larock. Comprehensive Organic Transformations: A Guide to Functional Group Preparations. VCH Publishers, New York, NY, 1989, 1.
    

Purification and analysis of organic compounds

ĶOS 550