Aminoacyl anions

Despite the presence of a formally divalent carbon atom, CO is not in fact a particularly reactive molecule and much of its chemistry depends on the use of either extreme conditions, energetic reagents or some form of catalysis. Perhaps the simplest examples of such catalysis are found in the reactions of carbon monoxide with protic reagents such as alcohols or secondary amines, affording esters or amides of formic acid. These reactions are catalyzed by alkoxide or amide anions, respectively, and, as shown in Scheme 1, the key step is nucleophilic attack on CO by the catalyst to give a strongly basic alkoxyacyl or aminoacyl anion which is immediately trapped by proton transfer from the alcohol or amine, so generating the catalytic species. 

The aminoacyl anions can also be generated as stoichiometric reagents in the foim of lithium derivatives which are stable at -75 C and react with a variety of electrophiles, including alkyl halides, aldehydes and ketones (Scheme 2)/ ... 

Electrochemical studies have demonstrated that formation of the )3-lactam (42) from the fl-aminoacyl iron complex (40) proceeds via initial formation of the anion (41) followed by sequential one-electron oxidations to give a transient iron(IV) complex which then collapses to (42) (Scheme 6) <840M1927>. 

In a subsequent transfer reaction, an co-aminoacyl lactam is produced with regeneration of a monomer anion ... 

The monomer anion can than attack either lactam monomer or the o>-aminoacyl lactam. In the latter case, however, the lactam ring is substituted by a second CO group. The reaction of the monomer anion with the polymer chain is lengthened by a monomeric unit ... 

Figure I Schematic views of reactions involved in peptide biosynthesis. (1) Adenylate formation involving nucleophilic attack of the carboxyl group at the a-phosphate of the MgATP --complex with release of MgPP. - (2) aminoacylation of the pantetheine cofactor by formation of the thio-late anion, attack of the mixed anhydride, and release of AMP (3) tentative view of the peptide bond formation by nucleophilic attack of the aminoacyl-nitrogen at the preceding thioester-car-boxyl, involving deprotonaiion-protonation (4) epimerization of an aminoacyl-thioester, a reaction differing from those catalyzed by the well-characterized amino acid racemases. (Altered from Ref. 13. )...

From the pH dependence of the reaction, the formation of a thiolate anion can be concluded (80, Figure 1). Both types of synthetases can be expected to have birrding sites for 4 -phosphopantetheine and, presumably, CoA. The possible transfer of acyl or aminoacyl residues to acyl cairier proteins (ACPs) has not been investigated. However, Heaton and Neuhaus (38) have uncovered a tmique mode of D-Ala attachment to tei-choic acids, consisting of a D-Ala adenylate-fcHming enzyme, a D-Ala carrier protein, and a respiective transferase. Both ACP from Eschencfiid colt and cre))tomyces erythreae also accepted the aminoacyl residue. 

An example of this reaction has been reported in which the alkylpalladium group is functionalized with a chlorobenzyl moiety, in which case intramolecular attack on the aminoacyl leads to a cyclic carbene ligand (Equation (22)). The structure of 56 has also been obtained and a Pd-G bond length of 2.01(2) A found. In both of the above cases, deprotonation of the carbon a to the carbene atom can be carried out, leading to formally anionic vinyl ligands. 

The free lactam cannot be acylated to give the (aminoacyl) lactam owing to the N-substituent. On the other hand, the anion of the initiating add (e.g.. Cl") can undergo acylation by the O-protonated lactam giving rise, for example, as described in reaction [31], to the acyl chloride of the amino acid ... 

Figure 14. (a) Semi-preparative anion-exchange HPLC on a RP-NH2-column of a nuclease digest of an aminoacyl-tRNA. Sample, 3 A2 units of a ribonuclease T1 digest of [ C]Phe-tRNA (yeast) column, LiChrosorb RP-NH2 (4.6 x 250 nm) apparatus, DuPont 850 liquid chromatograph with a DuPont UV spectrophotometer set at 260 nm with 1.28 AUFS elution, linear gradient from () to 0.1 M ammonium phosphate, pH 4.5, in 15 min, ftom 0.1 to 0.3 M ammonium phosphate, pH 4.5. in 10 min and from 0.3 to 1 M ammonium phosphate, pH 6.0, in 10 min flow-rate, 1.5 ml/min. Radioactivity was monitored off-... 

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