Department of Medical and Bioorganic Chemistry

1. Kharkov National Medical University Department of Medical and Bioorganic Chemistry Lecture Heterocyclic Compounds. Structure, Properties and Biological Function of Nucleic Acids

2. ACTUALITY OF THE LECTURE Heterocyclic structures are in the basis of numerous natural and biologically active substances and drugs. Heterocyclic molecules (indol, imidazole...) are included in some essential amino acids. A lot of drugs also contain heterocycles: non-narcotic analgesics contain pyrazolon-5, anti-tuberculosis drugs contain pyridine.

3. Outline of the lecture • Classification of heterocycles. • Aromaticity of heterocycles. • Biologically important compounds with five-membered heterocycles. • Biologically important compounds with six-membered heterocycles. • The structure and biochemical functions of nucleosides, nucleotides and nucleic acids.

4. HETEROCYCLIC COMPOUNDS are cyclic compounds in which an element other than carbon is present in the ring: Thiazole Furan Pyrrole

5. AROMATICITY OF HETEROCYCLES Hückel’s rule N = 4n + 2 where isn (number of cycles) = 1,2, etc. N - number of conjugate -electrons

6. 3. Biologicallyimportantcompounds withfive-memberedheterocyclesPorphine - tetrapyrrolearomaticringconstructedofpyrroline (I), pyrrole (III) andtwoizopirrolnyhnuclei (II, IV), connectedby a methinegroup = CH- Porphyrins (substitutedporphine) - prostheticgroupsofcomplexproteins: hemoglobin, myoglobin, mitochondrialrespiratoryenzymes - cytochrome, catalaseandperoxidase, chlorophyll, vitamin B12. 14 N N N N N N N N Porphine Porphyrine

7. USE IN MEDICINE Serotonin and tryptamine are biogenic amines, the products of the biochemical conversion of tryptophan in the body: N N 5-hydroxy triptophan Serotonin N Triptophan N Tryptamine

8. The main biologically active derivatives of imidazole are histidine and histamine N N N N

9. 4. Biologically important compounds with six-membered heterocycles:pyridine, pyrimidine, purine. N N N Picolinic acid Nicotinic acid Isonicotinic acid

10. ANTITUBERCULAR DRUG. N N Isoniazid Phthivazid

11. Barbituric acid (2,4,6-trihydroxypyrimidine) in water solutions can exist being in some tautomeric forms: • Lactam-lactim tautomerism, • keto-enol tautomerism: N N N N

12. BARBITURATES are drugs synthesized on the basis of barbituric acid. Phenobarbital (Luminal): R1 = C2H5; R2 = C6H5 Barbital (Veronal): R1 = R2 =C2H5 N N

13. IMPORTANT HETEROCYCLIC COMPOUNDS OF AMINOPURINES 6-aminopurine (adenine) 2-amino-6-hydroxypurine (guanine)

14. NUCLEIC ACIDS • Were discovered in 1868 by Swiss chemist F. Miescher • First found in the nucleus Friedrich Miescher

15. 5.The structure and biochemical functions of nucleosides and nucleotidesnucleic acid The structure of nucleic acids, monosaccharides are included in the β - furanose form:

16. NITROGEN BASES HN HN N 1 N N N 5

17. Primary structure of DNA 5’ 1’ 4’ 3’ 2’

18. 1953 Open structure of DNA Джеймс Уотсон Фрэнсис Крик

19. Francis Harry Compton Crick James Dewey Watson Nobel Prize 1962

20. TYPES OF RNA • transfer RNA (tRNA) - transporting of amino acids into the ribosome; • messenger RNA (mRNA) - is a matrix for protein synthesis; • ribosomal RNA (rRNA) - takes part in protein synthesis in ribosome.