Alanine alkylation

Using the corresponding (6R) isomer (from D-valine and DL-alanine), alkylation with 2-chloro-3-methyl quinoxaline followed by further transformation has yielded an aldose reductase inhibitor in optically pure form (90T7745). 

The synthesis of these compounds is performed by a simplified procedure which consists in coupling the various L-alanine alkyl esters with MDP, the carboxyl of which is previously activated by means of hydrosoluble carbodiimide in the presence of N-hydroxybenzotriazole. Almost pure products are obtained, and can be further purified either by ion-exchange chromatography for the less lipophilic or by silica gel chromatography for the more lipophilic derivatives. 

The nonpolar amino acids (Figure 4.3a) include all those with alkyl chain R groups (alanine, valine, leucine, and isoleucine), as well as proline (with its unusual cyclic structure), methionine (one of the two sulfur-containing amino acids), and two aromatic amino acids, phenylalanine and tryptophan. Tryptophan is sometimes considered a borderline member of this group because it can interact favorably with water via the N-H moiety of the indole ring. Proline, strictly speaking, is not an amino acid but rather an a-imino acid. 

Amino acids can be prepared by reaction of alkyl halides with diethyl acelamidomalonate, followed by heating the initial alkylation product with aqueous 1-ICl. Show how you would prepare alanine, CH3CH(NH2)C02H, one of the twenty amino acids found in proteins, and propose a mechanism for acid-catalyzed conversion of the initial alkylation product to the amino acid. 

DNA sequencing and. 1113 Electrospray ionization (ESI) mass spectrometry, 417-418 Electrostatic potential map, 37 acetaldehyde, 688 acetamide, 791,922 acetate ion. 43. 53, 56, 757 acetic acid. 53. 55 acetic acid dimer, 755 acetic anhydride, 791 acetone, 55, 56. 78 acetone anion, 56 acetyl azide, 830 acetyl chloride, 791 acetylene. 262 acetylide anion, 271 acid anhydride, 791 acid chloride, 791 acyl cation, 558 adenine, 1104 alanine, 1017 alanine zwitterion, 1017 alcohol. 75 alkene, 74, 147 alkyl halide, 75 alkyne. 74... 

Photodriven reactions of Fischer carbenes with alcohols produces esters, the expected product from nucleophilic addition to ketenes. Hydroxycarbene complexes, generated in situ by protonation of the corresponding ate complex, produced a-hydroxyesters in modest yield (Table 15) [103]. Ketals,presumably formed by thermal decomposition of the carbenes, were major by-products. The discovery that amides were readily converted to aminocarbene complexes [104] resulted in an efficient approach to a-amino acids by photodriven reaction of these aminocarbenes with alcohols (Table 16) [105,106]. a-Alkylation of the (methyl)(dibenzylamino)carbene complex followed by photolysis produced a range of racemic alanine derivatives (Eq. 26). With chiral oxazolidine carbene complexes optically active amino acid derivatives were available (Eq. 27). Since both enantiomers of the optically active chromium aminocarbene are equally available, both the natural S and unnatural R amino acid derivatives are equally... 

Before analyzing in detail the conformational behaviour of y9-peptides, it is instructive to look back into the origins and the context of this discovery. The possi-bihty that a peptide chain consisting exclusively of y9-amino acid residues may adopt a defined secondary structure was raised in a long series of studies which began some 40 years ago, on y9-amino acid homopolymers (nylon-3 type polymers), such as poly(/9-alanine) 3 [14, 15], poly(y9-aminobutanoic acid) 4 [16-18], poly(a-dialkyl-/9-aminopropanoic acid) 5 ]19], poly(y9-L-aspartic acid) 6 ]20, 21], and poly-(a-alkyl-/9-L-aspartate) 7 [22-36] (Fig. 2.1). 

Alternative routes to -amino acids have also been explored and involve, stereoselective alkylation of chiral derivatives of y9-alanine [136-140], Curtius rearrangement of enantiomerically pure and regioselectively protected substituted-succinic acids [134, 141, 142] (the approach is also suitable for the synthesis of y9 -amino acids [143]), or the formation of chiral isoxazolidinone intermediates [144]. 

Alanine, valine, and leucine, (amino-acids with alkyl substituents only) react in a manner very like that of glycine (49—53). All the reactions are rather slow and boiling solutions are normally employed in the preparative reactions. With the cis- and /raws-isomers of Pt(NHs)2Cl2 substitution of the chloride only occurs. Since the tfraws-labilising influence of the incoming groups of the amino-acids is very small, the —NH2 groups remain stable. Consequently chelated complexes are only formed by the amino-acids in the case of the cts-isomer. 

R Lygo, J. Crosby, J. A Peterson, Enantioselective Alkylation of Alanine-Derived Imines Using Quaternary Ammonium Catalysts , Tetrahedron Lett. 1999, 40, 8671-8674. 

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