If I could make things in a beaker then surely this I what I would do.

1. If I could make things in a beakerthen surely this I what I would do. Stuff we do in glassware that copies nature

2. 19.3 Synthesis of Amino Acids The Amidomalonate Synthesis • Used for synthesizing a-amino acids: Amidomalonate synthesis of amino acids is an extension of the malonic ester synthesis • Conversion of diethyl acetamidomalonate into an enolate ion by treatment with a base • SN2 alkylation with a primary alkyl halide • Hydrolysis of both the amide group and the esters occurs when the alkylated product is warmed with aqueous acid • Decarboxylation takes place to yield an a-amino acid Preparation of aspartic acid from ethyl bromoacetate, BrCH2CO2Et • Reaction yields a racemate

3. Synthesis of Amino Acids Reductive Amination of a-Keto Acids • Another method of synthesizing a-amino acids • Reduces an a-keto acid with ammonia and a reducing agent • Preparation of alanine by treatment of pyruvic acid with ammonia in the presence of NaBH4 • Reaction proceeds through formation of an intermediate imine that is then reduced • Reaction yields a racemate

4. 19.7 Peptide Synthesis During the course of a peptide synthesis, many different amide bonds must be formed in a specific order • The solution of the specificity problem is to protect some functional groups rendering them unreactive while leaving exposed only those functional groups wanted for reaction • To synthesize Ala-Leu, by coupling alanine with leucine • Protect the –NH2 group of alanine and the –CO2H group of leucine to render them unreactive • Form the desired amide bond • Remove the protecting groups

5. Peptide Synthesis Amino- and carboxyl-protecting groups • Carboxyl groups are often protected by converting them into methyl or benzyl esters • Both groups are easily introduced by standard methods of ester formation • Both groups are easily removed by mild hydrolysis with aqueous NaOH • Benzyl esters can also be cleaved by catalytic hydrogenolysis of the weak benzylic C-O bond (RCO2–CH2Ph + H2 PhCH3)

6. Peptide Synthesis • Amino groups are often protected as their tert-butoxycarbonyl amide, or Boc, derivatives • Protecting group is introduced by reaction of the amino acid with di-tert-butyl dicarbonate in a nucleophile acyl substitution reaction • Protecting group is removed by brief treatment with a strong organic acid such as trifluoroacetic acid, CF3CO2H

7. Peptide Synthesis Five steps are needed to synthesize a dipeptide such as Ala-Leu using the Boc protecting group

8. Merrifield solid-phase method simplifies the synthesis of a large peptide chain Peptide synthesis is carried out with the growing amino acid chain covalently bonded to small beads of polymer resin In the original Merrifield procedure, polystyrene resin was used 1 of every 100 or so benzene rings contained a chloromethyl (-CH2Cl) group A Boc-protected C-terminal amino acid was bonded to the resin through an ester bond formed by SN2 reaction Peptide Synthesis

9. Peptide Synthesis • With the first amino acid bonded to resin, a repeating series of four steps is carried out to build a peptide

10. Peptide Synthesis

11. Peptide Synthesis The most commonly used resins at present are the Wang resin or the PAM (phenylacetamidomethyl) resin • The most commonly used N-protecting group is the fluorenylmethyloxycarbonyl, or Fmoc group

12. Peptide Synthesis Robotic, computer-controlled peptide synthesis used to automatically repeat the coupling, washing, and deprotection steps with different amino acids • Each step occurs in high yield • The peptide intermediates are never removed from the insoluble polymer until the final step • Using this procedure, up to 30 mg of a peptide with 20 amino acids can be routinely prepared

13. 21.6 Reactions of Monosaccharides Ester and Ether Formation • Monosaccharides exhibit chemistry similar to simple alcohols • Usually soluble in water but insoluble in organic solvents • Do not easily form crystals upon removal of water • Can be converted into esters and ethers • Ester and ether derivatives are soluble in organic solvents and are easily purified and crystallized

14. Reactions of Monosaccharides • Esterification is normally carried out by treating the carbohydrate with an acid chloride or acid anhydride in presence of base • All –OH groups react including the anomeric –OH group

15. Reactions of Monosaccharides Carbohydrates are converted into ethers by treatment with an alkyl halide in the presence of base – the Williamson ether synthesis • Silver oxide (Ag2O) gives high yields of ethers without degrading the sensitive carbohydrate molecules

16. Reactions of Monosaccharides Glycoside Formation • Hemiacetals yield acetals upon treatment with an alcohol and an acid catalyst • Treatment of monosaccharide hemiacetals with an alcohol and acid catalyst yields an acetal, called a glycoside

17. Reactions of Monosaccharides Reduction of Monosaccharides • Treatment of an aldose or ketose with NaBH4 reduces it to a polyalcohol called an alditol • Reduction occurs by reaction of the open-chain form present in aldehyde/ketone hemiacetal equilibrium • D-Glucitol, also known as D-sorbitol, is present in many fruits and berries and is used as a sweetener and sugar substitute

18. Reactions of Monosaccharides Oxidation of Monosaccharides • Aldoses are easily oxidized to yield corresponding carboxylic acids called aldonic acids • Oxidizing agents include: • Tollen’s reagent (Ag+ in aqueous NH3) • Gives shiny metallic silver mirror on walls of reaction tube or flask • Fehling’s reagent (Cu2+ in aqueous sodium tartrate) • Gives reddish precipitate of Cu2O • Benedict’s reagent (Cu2+ in aqueous sodium citrate) • Gives reddish precipitate of Cu2O (All three reactions serve as simple chemical tests for reducing sugars)

19. Reactions of Monosaccharides • Fructose is a ketose that is a reducing sugar • Undergoes two base-catalyzed keto-enol tautomerizations that result in conversion to a mixture of aldoses (glucose and mannose)

20. Reactions of Monosaccharides • Br2 is a mild oxidant that gives good yields of aldonic acid products • Preferred over Tollen’s reagent because alkaline conditions in Tollen’s oxidation cause decomposition of the carbohydrate

21. Reactions of Monosaccharides • Aldoses are oxidized in warm, dilute HNO3 to dicarboxylic acids called aldaric acids • Both the –CHO group at C1 and the terminal –CH2OH group are oxidized

22. Reactions of Monosaccharides • Enzymatic oxidation at the –CH2OH end of aldoses yields monocarboxylic acids called uronic acids • No affect on the –CHO group

23. Waxes, Fats, and Oils The conversion of linoleic acid into elaidic acid

24. 23.2 Soap Soap has been known since at least 600 BC • Phoenicians prepared a curdy material by boiling goat fat with extracts of wood ash • Wood ash was used as a source of alkali until the early 1800s when Na2CO3 was made by heating sodium sulfate with limestone • Cleansing properties of soap were not generally recognized until the 18th century • Soap is a mixture of sodium or potassium salts of long-chain fatty acids produced by hydrolysis (saponification) of animal fat with alkali

25. 24.7 DNA Synthesis Synthesis of short DNA segments, called oligonucleotides or oligos • A nucleotide has multiple reactive sites that must be selectively protected and deprotected at the proper times • Coupling of the four nucleotides must be carried out in the proper sequence • Automated DNA synthesizers allow the fast and reliable synthesis of DNA segments up to 200 nucleotides in length • A protected nucleotide is covalently bonded to a solid support • One nucleotide at a time is added to the growing chain by the use of a coupling reagent • After the final nucleotide has been added, all the protecting groups are removed and the synthetic DNA is cleaved from the solid support

26. DNA Synthesis Step 1 Attachment of a protected deoxynucleoside to a silica (SiO2) support • Done through an ester linkage to the 3′ –OH group of the deoxynucleoside • Both the 5′ –OH group on the sugar and free –NH2 groups on the heterocyclic bases must be protected • The deoxyribose 5′ –OH is protected as its p-dimethoxytrityl (DMT) ether

27. DNA Synthesis • Adenine and cytosine bases are protected by benzoyl groups • Guanine is protected by an isobutryl group • Thymine requires no protection

28. DNA Synthesis Step 2 Removal of the DMT protecting group by treatment with dichloroacetic acid in CH2Cl2 • Reaction occurs by an SN1 mechanism • Reaction proceeds rapidly due to the stability of the tertiary, benzylic dimethoxytrityl cation

29. DNA Synthesis Step 3 Coupling of the polymer-bonded deoxynucleoside with a protected deoxynucleoside containing a phosphoramiditegroup, R2NP(OR)2, at the 3′ position • Takes place in the polar aprotic solvent acetonitrile • Requires catalysis by the heterocyclic amine tetrazole • Yields a phosphite, P(OR)3

30. DNA Synthesis Step 4 Oxidation • Phosphite product is oxidized to a phosphate by treatment with iodine in aqueous tetrahydrofuran in the presence of 2,6-dimethylpyridine • The cycle is repeated until oligonucleotide chain of the desired sequence is built • Deprotection • Coupling • Oxidation

31. DNA Synthesis Step 5 Final step • Removal of all protecting groups • Cleavage of the ester bond holding the DNA to the silica • All reactions are done at the same time by treatment with aqueous NH3 • Purification by electrophoresis yields the synthetic DNA