Reaction with ammo acids

An example of a biologically important aide hyde is pyridoxal phosphate which is the active form of vitamin Bg and a coenzyme for many of the reac tions of a ammo acids In these reactions the ammo acid binds to the coenzyme by reacting with it to form an imine of the kind shown in the equation Re actions then take place at the ammo acid portion of the imine modifying the ammo acid In the last step enzyme catalyzed hydrolysis cleaves the imme to pyridoxal and the modified ammo acid... 

If only very small samples of ammo acids are available for analysis, fluorescence IS used for detection. One of the most sensitive methods of mi-croanalysis is based on the reaction of ammo acids with o-phthalaldehyde and /3-mercaptoethanol (Equation E2.1). The isoindole derivative is fluorescent and amounts as small as 10 mole may be measured... 

French, D, and Edsall, J. T. (1945) The reactions of formaldehyde with ammo acids and proteins. Adv Protein Chem, 2,278... 

Although this reaction is useful for preparing a ammo acids (Table 22 3 fifth entry) it IS not a general method for the synthesis of amines Its major limitation is that the expected primary amine product is itself a nucleophile and competes with ammonia for the alkyl halide... 

A novel technique for dating archaeological samples called ammo acid racemiza tion (AAR) IS based on the stereochemistry of ammo acids Over time the configuration at the a carbon atom of a protein s ammo acids is lost m a reaction that follows first order kinetics When the a carbon is the only chirality center this process corresponds to racemization For an ammo acid with two chirality centers changing the configuration of the a carbon from L to D gives a diastereomer In the case of isoleucme for example the diastereomer is an ammo acid not normally present m proteins called alloisoleucme... 

In the Strecker synthesis an aldehyde is converted to an a ammo acid with one more carbon atom by a two stage procedure m which an a ammo nitrile is an mterme diate The a ammo nitrile is formed by reaction of the aldehyde with ammonia or an ammonium salt and a source of cyanide ion Hydrolysis of the nitrile group to a car boxylic acid function completes the synthesis... 

Step 2 On reaction with hydrogen chloride m an anhydrous solvent the thiocarbonyl sulfur of the PTC derivative attacks the carbonyl carbon of the N terminal ammo acid The N terminal ammo acid is cleaved as a thiazolone derivative from the remainder of the peptide... 

The p nitrophenol formed as a byproduct in this reaction is easily removed by extrac tion with dilute aqueous base Unlike free ammo acids and peptides protected peptides are not zwitteriomc and are more soluble m organic solvents than m water... 

Memfield successfully automated all the steps m solid phase peptide synthesis and computer controlled equipment is now commercially available to perform this synthesis Using an early version of his peptide synthesizer m collaboration with coworker Bemd Gutte Memfield reported the synthesis of the enzyme ribonuclease m 1969 It took them only SIX weeks to perform the 369 reactions and 11 391 steps necessary to assemble the sequence of 124 ammo acids of ribonuclease... 

This reaction forms the basis of one method of terminal residue analysis A peptide is treated with excess hydrazine in order to cleave all the peptide linkages One of the terminal amino acids is cleaved as the free amino acid and identified all the other ammo acid residues are converted to acyl hydrazides Which amino acid is identified by hydrazmolysis the N terminus or the C terminus ... 

As in the synthesis of (+)-26 (Scheme 8), treatment of (-)-27 with chromic acid accomplishes oxidative scission of the carbon-carbon double bond, and provides (-)-26 after an intramolecular bislactonization reaction (Scheme 16). By analogy to the conversion of 50 into 51 (see Scheme 8), treatment of (-)-26 with ammo-... 

The vinyl triflate of Komfeld s ketone has been subjected to Heck reactions with methyl acrylate, methyl methacrylate, and methyl 3-(7V-fert-butoxycarbonyl-A -methyl)ammo-2-methylenepropionate leading to a formal synthesis of lysergic acid [259]. A similar Heck reaction between l-(phenylsulfonyl)indol-5 yl triflate and dehydroalanine methyl ester was described by this research group [260]. Chloropyrazines undergo Heck couplings with both indole and 1-tosylindole, and these reactions are discussed in the pyrazine Chapter [261]. Rajeswaran and Srinivasan described an interesting arylation of bromomethyl indole 229 with arenes [262]. Subsequent desulfurization and hydrolysis furnishes 2-arylmethylindoles 230. Bis-indole 231 was also prepared in this study. 

A wide variety of a-tnfluoromethyl ab-ammo acids ate readily available from the reaction of 5-fluoro-4-tnfluoromethyl-l,3 azoles with allyhc alcohols [755, 759] a-Tnfluoromethyl-substituted a-amino acids show antibacterial and antihy pertensive activity Some are highly specific enzyme inhibitors (suicide inhibitors) and may be important as bioregulators [740] Furthermore, they are interesting candidates for peptide modification... 

Tips Which is the most nucleophilic position in compound 6, assuming that the ammo acid is present in the neutral form depicted The added aldehyde initially undergoes nucleophilic attack. Water is removed from the reaction mixture with the aid of a separator. Compound 7 is a bicyclic molecule... 

Cyclization to a morpholinolactone (59) occurs in the hydrolysis reaction of the di-A-hydroxylethylated compound (60). Compound (59) is rapidly hydrolysed by water to (61) but in file presence of equimolar amounts of amines (RNH2) or ammo acid derivatives (62) forms.56 A novel reaction of cyclic 2-diazo-l,3-dicarbonyl compounds (63) with lactones (64) affords the products (65) in the presence of rhodium acetate, Rh2(OAc)4.57 Lewis acid-promoted intramolecular additions of allylsilanes to lilac tones gave substituted cyclopentanes.58 A proposed transition state guided efforts to improve the stereoselectivity of the reaction. The reaction of a series of /1-lactone derivatives, such as (66)-(68), has been studied and they have been ling cleaved the reaction outcome is both Lewis acid and structure dependent.59... 

The kinetics of alkylation by benzyl bromide of the Schiff base esters of ammo acids (Ph2C=NCH2CC>2CMe3) in the presence of cinchona salts show features similar to those of enzyme-promoted reactions variable orders, substrate saturation, catalyst inhibition, and non-linear Arrhenius-type plots.125 A tight coordination of the Schiff base substrate by electrostatic interaction with the quaternary N of the cinchona salt provides a favourable chiral environment for asymmetric alkylation. 

For the resolution of cyanopentafluorophenylethanol with lipase, (he reaction temperature was decreased to improve the enantioselectivities (Figure 15(b)). The ameso comPounds were conducted to obtain fluorinated amino, . "UIC. 1 > e)). Esterification of meso alcohol gave the corresponding W-ammo acid, whereas the hydrolysis gave the corresponding(5)-product. 

W-(Methoxycarbonyl)triphenylphosphine imide reacts with methyl trifluoro-pyruvate to form methyl N-methoxycarbonyl 2 imino-3,3,3 trifluoropropionate m 95% yield This convenient building block easily adds nucleophiles such as Grignard reagents without competing side reactions at the ester group to form trifluoromethylated ammo acids [3.S] (equation 31)... 

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