TASHKENT MEDICAL ACADEMY Department of Bioorganic and Biological Chemistry Bioorganic chemistry I COURSE SUBJECT: carbonyl compounds and their characteristic reaction LECTURE№5 LECTURER : PROFESSOR A.D.DZHURAEV

PURPOSE OF LECTURES: Form of knowledge of chemical properties of carbonyl compounds to understand their reactivity, causing a flow of a series of reactions in biological systems.

The questions of: 1. The reactivity of carbonyl compounds 2. The establishment of the reaction centers in aldehydes and ketones 3. Factors affecting the activity of aldehydes and ketones 4. Nucleophilic addition reactions typical of aldehydes and ketones 5. Biologically active compounds in a series of aldehydes and ketones 6. The reactivity of carboxylic acids 7. Reaction sites in carboxylic acids 8. Factors affecting the activity of carboxylic acids 9. Nucleophilic substitution reactions typical of carboxylic acids and their derivatives 10. Biologically active compounds of carboxylic acids and their functional derivatives

Reaction centers in aldehydes and ketones  + --.. basic (nucleophilic) center electrophilic center CH-acidic center О (H) C C R ++ :

Structure of the carbonyl group p - orbitals

Nucleophilic addition reaction (А N ) 1. Hydration reaction basic center acid sites hydrate formaldehyde chloral hydrate

2. Addition of an alcohol (Obtaining acetal) hemiacetals Full Acetal

А N Mechanism : Full Acetal hemiacetals

Hydrolysis of the acetal:

3. Accession thiol polimerkapital Full mercaptan

4. Connection of primary amines Basis. center acid sites base Schiff (imine)

5. Reduction to alcohols: hydride sodium alkoxy propanol-2

6. Aldol condensation Н-СОН СCI 3 – СОН СН 3 - СОН СН 3 - СН 2 -СОН C O Н

The reaction mechanism of aldol condensation alkoxide ion

Reaction sites in carboxylic acids and their derivatives О (H) C C Х basic center electrophilic center CH-acidic centerThe leaving group --  + ++ :..

Carboxylic anhydride

Simple anhydride - identical acids contain residues R-CO-OCO-R Mixed anhydride - contain residues of various acids R-CO-OCO-R"

Reaction esterification (А N ) The esterification reaction – The reaction between the alcohol and acid to form an ester

The reaction mechanism of esterification: ethyl acetate

Oxidation of organic compounds CH 4 CH 3 Cl CH 2 Cl 2 CHCl 3 CCl 4  СН 3 < CH 2 < CH CН 4 < CH 3 OH<CH 3 NH 2 С  С  < C  C Increasing the degree of oxidation of the carbon atom Increase the tendency to oxidize Increased propensity to oxidation sp 3 carbon atom sp 2 carbon atom Increased propensity to oxidation

Oxidation of the C-H bond СН 4 СН 3 –О Н H – C R – C O O HOH [O][O] [O] [H][H] [H] The oxidation of primary carbon Oxidation of the secondary carbon atom Oxidation of the tertiary carbon atom СН 3 СН 3 СН 3 С – Н СН 3 С – ОН СН 3 СН 3 СН 3 –СН 2 –СН 3 СН 3 –СН–С Н 3 СН 3 –С–СН 3 ОН О secondary alcohol ketone isobutanolTertiary. butyl alcohol

Oxidation of alkanes R – H + O 2 = R – O – O – H substratum hydroperoxide  С  Н + О 2 + НАДФН + Н +   С  ОН+ Н 2 О+ НАДФ + НАД + + Н – substratum– Н  НАДН + substratum+ Н + For the oxidation of alcohols: НАД + +Н – С – ОН  НАДН + >С=О + Н +

The coenzymes oxidoreduction + N CONH 2 R + H – substratum– Н recovery. form CONH 2 N R НН + Н + + Substrate oxidation. form N NH O N NNN N N RR H H H CH 3 O OO НАД + НАДН ФАД ФАДН 2 +2Н - 2Н

Dehydrogenation of organic compounds ФАД+RCH 2 CH 2 -C-SКoA ФАДН 2 +RCH=CH -C- SКoA   O О Oxidation of unsaturated hydrocarbons >C C C = C C --- C< O alkene epoxide >C=O + O=C< carbonyl compounds ОН ОН 1,2- diol

Oxidation of aromatic hydrocarbons О О ОН +2е; +2Н + -2е; -2Н +

Recovery of organic compounds НАДН + Н + + R-C-H  НАД + + R-CH 2 -OH  O Oxidation of nitrogen-containing compounds RCH 2 NH 2 RCH=NH R-C-H + NH 3 RNH 2  [RNHOH]  [RN=O]  RNO 2 Amin Hydroxylamine Nitrosamines nitro. -ФАДН 2 ФАД H2OH2O  O Amine oxidation deamination

Oxidation of thiols  О R-SH R-S-OH R-S-OH R-S-OH R-SH  R-S-S-R О О   Thiol sulfite к-та sulfinyl к-та sulfone к-та Mild oxidation of thiols