Classification, structure and biological role of heterocyclic compounds and of nucleic acids Lecturer: Bekus Iryna

Heterocyclic compounds are cyclic compounds in which one or more ring atoms are not carbon (that is hetero atoms). As hetero atom can be N, О, S, В, Al, Si, P, Sn, As, Cu. But common is N, О, or S.

Classification Heterocycles are conveniently grouped into two classes, nonaromatic: and aromatic

By size of ring Three-membered Four-membered Five-membered Six-membered

Tetrapyrrole compounds blood heme

Five - membered heterocyclic compounds with one heteroatom. The structures of these three heterocyclic would suggest that they have highly reactive diene character. These heterocyclic have characteristics associated with aromaticity. From an orbital point of view, pyrrole has a planar pentagonal structure in which the four carbons and the nitrogen have sp² hybridization. Each ring atom forms two sp²—sp²  bonds to its neighboring ring atoms, and each forms one sp² – s  bond to a hydrogen.

1. Cyclization of 1,4-dicarbones compounds Methods of synthesis of five - membered heterocyclec compounds with one heteroatom. 1. Cyclization of 1,4-dicarbones compounds C H 2 R O P S 5 N 3 4 c.

Formation of furan: In laboratory conditions furan is produced by dry distillation of mucic acid. In the industry furan derived from aldopentozes

Formation of thiophene Thiophene is prepared industrially by passing а mixture of butane, butene, or butadiene and sulfur through a reactor heated at 600' for а contact time of about 1 sec + H2 S n- C4H10 + S =

Physical properties of furan, pyrrole, thiophene At room temperature, thiophene is a colorless liquid with a mildly pleasant odor reminiscent of benzene, with which thiophene shares some similarities. Like benzene, thiophene forms an azeotrope with water. Furan is typically derived by the thermal decomposition of pentose-containing materials, cellulosic solids especially pine-wood. Furan is a colorless, flammable, highly volatile liquid with a boiling point close to room temperature. It is toxic and may be carcinogenic. Pyrrole is a heterocyclic aromatic organic compound. Substituted derivatives are also called pyrroles. Porphobilinogen is a trisubstituted pyrrole, which is the biosynthetic precursor to many natural products

Chemical properties of furan, pyrrole, thiophene The typical reaction of furan, pyrrole, and thiophene is electrophilic substitution. All three heterocycles are much more reactive than benzene. The reactivity order being is: To give some idea of the magnitude of this reactivity order, partial rate factors (reactivities relative to benzene) for tritium exchange with fluoroacetic acid.

Reciprocal transformation of furan, pyrrole, thiophene (Yurie`s cycle reactions) пірол H2S NH3 NH3 H2O H2S H2O Thiophene Furan

1. Interaction with dilute mineral acids Pyrroles are polymerized by even dilute acids, probably by a mechanism such as the following . 2. Reactions of electrophilic substitution: This orientation is understandable in terms of the mechanism of electrophilic aromatic substitution. The / ratio is determined by the relative energies of the transition states leading to the two isomers. As in the case of substituted benzenes, we may estimate the relative energies of these two transition states by considering the actual reaction intermediates produced by attack at the -or -positions.

Nitration 2-nitropyrrole

Sulfonation

Acylation 2-acetylpyrrole Because of this high reactivity, even mild electrophiles to cause reaction. Substitution occurs predominantly at the α-position (С-2).

Of these structures, the most important are the two with the positive charge on sulfur because, in these two sulfonium cation structures, all atoms have octets of electrons. Nevertheless, as the sets of resonance structures show, the charge on the cation resulting from attack at the -position is more extensively delocalized than that for the cation resulting from attack at the -position. The following examples further demonstrate the generality of -attack.

Halogenation In the last example, note that 2-iodothiophene is the sole product of iodination, eyeu though the reaction is carried out in benzene as solvent; that is, thiophene is so much more reactive than benzene that no significant amount of iodobenzene is formed.

Reactions of reconstruction Thiophen are more stable and do not undergo hydrolysis. Reduction of pyrrole:

Reactions of oxidation

For identification of pyrrole and furan used the method coloring of a pine chip. Couples of pyrrole painted a pine chip soaked in hydrochloric acid in the red colour and furan - in the green colour. Qualitative reaction on thiophene is indophenin`s reaction: a mixture of izathine with concentrated sulfuric acid painted in the blue colour.

The important derivatives of pyrrole, furan and thiophene.

The important derivatives of pyrrole, furan and thiophene. tetrahidrothiofene biotin

Five-membered heterocyclec with two heteroatoms pyrazole Imidazole thiazole

Six-membered heterocyclic compounds pyridine group Pyridine quinoline nicotinic acid nicotinamide

Six-membered heterocycles with two heteroatoms pyrazine pirydazine pyrimidine

Characteristic for pyridine reactions can be divided into three groups: Reactions which followings with participation of heteroatom. 2) Reactions of substituting for the hydrogen atoms of pyridines ring. 3) Reactions of reduction and oxidization.

Reactions which followings with participation of heteroatom. 1. Cooperating with acids. Due to the indivisible pair of electrons atom of nitrogen of pyridine shows weak basic properties. At cooperating with strong mineral and organic acids he forms soluble salt of pyridine. 2. Reaction with the oxide of sulphur (VI). pyridine bromide

Reactions of reduction and oxidization. pyperedine nicotinic acid

Reactions of substituting for the hydrogen atoms of pyridines ring. 1. Reactions of electrophilic substitution (SE). The reactions of nitration, sulphonation and halogenation pass slowly drastic and with low exits. Thus an electrophilic reagent is direct in position 3. 3-nithropyridine 3-pyridinesulphure acid

These ring systems, particularly that of pyrimidine, occur commonly in natural products. The pyrimidines, cytosine, thymine, and uracil are especially important because they are components of nucleic acids, as are the purine derivatives adenine and guanine.

Nucleic acids A Nucleic acids are polymers of nucleotides joined by 3',5' -phosphodiester bonds; that is, a phosphate group links the 3' carbon of a sugar to the 5' carbon of the next sugar in the chain. A phosphate group is often found at the 5' end, and a hydroxyl group is often found at the 3' end.

Types of nucleic acids. Two types of nucleic acids are found within cells of higher organisms: deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Nearly all the DNA is found within the cell nucleus. Its primary function is the storage and transfer of genetic information. This information is used (indirectly) to control many functions of a living cell. In addition, DNA is passed from existing cell to new cells during cell division RNA occurs in all parts of a cell. It functions primarily in synthesis of proteins, the molecules that carry out essential cellular functions.

The monomers for nucleic acid polymers, nucleotides, have а more complex structure than polysaccharide monomers (monosacharides) or protein monomers (amino acids). Within each nucleotide monomer are three subunits. А nucleotide is, а molecule composed of a pentose sugar bonded to both a group and a nitrogen-containing hetero-cyclic base.

Pentose sugars. The sugar unit of а nucleotide is either the pentose ribose or the 2-deoxyribose.

Nitrogen-containing bases. Five nitrogen-containing bases are nucleotide components. Three of them are derivatives of pyrimidine, а monocyclic base with а six-membered ring, and two are derivatives of purine, а bicyclic base with fused five- and six-membered rings.

Nucleosides are compounds formed when a base is linked to a sugar via a glycosidic bond.

                                                                    Uridine Cytidine Thymidine

Nucleotide A nucleotide results when phosphoric acid is esterified to a sugar OOH group of a nucleoside. The nucleoside ribose ring has three OOH groups available for esterification, at C-2, C-3, and C-5 (although 2-deoxyribose has only two). The vast majority of monomeric nucleotides in the cell are ribonucleotides having 5-phosphate groups.

Nucleotide formation. The formation of а nucleotide from sugar, base, and phosphate can be visualized as occurring in the following manner:

Nucleotide nomenclature.

There are two major classes of nucleic acids – DNA and RNA. DNA has only one biological role, but it is the more central one. The information to make all the functional macromolecules of the cell (even DNA itself) is preserved in DNA and accessed through transcription of the information into RNA copies. Coincident with its singular purpose, there is only a single DNA molecule (or “chromosome”) in simple life forms such as viruses or bacteria. Such DNA molecules must be quite large in order to embrace enough information for making the macromolecules necessary to maintain a living cell RNA has a number of important biological functions, and on this basis, RNA molecules are categorized into several major types: messenger RNA, ribosomal RNA, and transfer RNA. Eukaryotic cells contain an additional type, small nuclear RNA (snRNA).

DNA The DNA isolated from different cells and viruses characteristically consists of two polynucleotide strands wound together to form a long, slender, helical molecule, the DNA double helix. The strands run in opposite directions; that is, they are antiparallel and are held together in the double helical structure through interchain hydrogen bonds

DNA molecules are the carriers of the genetic information within а cell; that is, they the molecules of heredity. Each time а cell divides, an exact copy of the DNA of the present cell is needed for the new daughter cell. The process by which new DNA molecule generated is DNA replication DNA replication is the process by which DNA molecules produce exact duplicates of themselves. The key concept in understanding DNA replication is the base pairing associated with the DNA double helix. We can divide the overall process of protein synthesis into two steps. The first step is called transcription and the second translation. Transcription is the process by which DNA directs the synthesis of RNA molecules that carry the coded information needed for protein synthesis. Translation is the process by which the codes within RNA molecules are deciphered and а particular protein molecule is formed. The following diagram summarizes the relationship between transcription and translation.

DNA to RNA Transcription The DNA contains the master plan for the creation of the proteins and other molecules and systems of the cell, but the carrying out of the plan involves transfer of the relevant information to RNA in a process called transcription. The RNA to which the information is transcribed is messenger RNA (mRNA).

Ribonucleic acids (RNA). Four major differences exist between RNA molecules and DNA molecules. The sugar unit in the backbone of RNA is ribose; it is deoxyribose in DNA. The base thymine found in DNA is replaced by uracil in RNA. Uracil, instead of thymine, pairs with (forms hydrogen bonds with) adenine in RNA. RNA is а single-stranded molecule; DNA is double-stranded (double helix). Thus RNA, unlike DNA, does not contain equal amounts of specific bases. RNA molecules are much smaller than DNA molecules, ranging from as few as 75 nucleotides to а few thousand nucleotides.

Differences exist between RNA molecules and DNA molecules.

Types of RNA

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