Dialkylamino acid

For a,a-dialkylamino acids enantiomerization is not a problem. The preparation of 4,4-dimethyl-2-[(9-fluorenylmethyl)oxy]-5(4F/)-oxazolone, an intermediate used in the synthesis of ( )-mirabazole C has been described. Recently, two new 2-aIkoxy-5(4F/)-oxazolones derived from Toac (2,2,6,6-tetramethyl-4-amino-l-oxy-piperidine-4-carboxylic acid) that incorporate Z or 9-fluorenylmethoxycarbonyl (Fmoc) protection at C-2 have been described. The Toac analogues were synthesized as part of a study of the crystal structure and ab initio calculations for these interesting systems. 

Table 7.3 Enantioselective synthesis of a,a-dialkylamino acid derivatives using salen-Cu(I I) complexes effect of metal and base.

Table 7.4 a,a-Dialkylamino acid derivatives by asymmetric alkylation of imines 40a and 40b utilizing salen-Cu(ll) complex 39c. 

Table 7.5 Enantioselective synthesis ofa.a-dialkylamino acid derivatives using39c substrate scope.

The efficiency of the fluoride method was further confirmed by the synthesis of pep-taibols. These peptides are characterized by a high content of the C -dialkylamino acids Aib or isovaline and an amino alcohol at the C-terminus such as phenylalaninol (Pheol) or valinol (Valol). Degradation of the peptides in the final cleavage step due to the acid-labile Aib-Pro linkages,can be prevented by the use of the 2-chlorotrityl-resin.P l This achieves direct anchoring of Fmoc-protected amino alcohols which allows the final cleavage to occur under very mild conditions.P l... 

Numerous bases can be used, particularly DIPEA or NMM. In the case of fragment coupling, other tertiary amines, such as collidine, are recommended to decrease the degree of epimerization.t Addition of DMAP improves the halophosphonium-mediated activation of a,a-dialkylamino acids. 

The same conclusion applies for L-alanine/pyruvate (2S7), pyridoxamine/pyru-vate (238), and dialkylamino acid transaminase (239). Second, small but significant amounts of direct hydrogen transfer (as either or H) between the a-carbon and C-4 have been detected during catalysis by the latter two enzymes (238, 239). Thus, the clear implication of these results is that a single active site base operating at the si face of the aldimine facilitates proton transfer between the a-carbon and C-4 [Eq. (47)]. 

Zhao, M. Bada, J. L. Determination of a-Dialkylamino Acids and Their Enantiomers in Geological Samples by High Performance Liquid Chromatography After Derivatization with a Chiral Adduct of O-Phthalaldehyde. J. Chromat. A 1995, 690, 55-63. 

General procedure The dialkylamino acid (1 part) is dissolved in acetic anhydride (4 parts) or in a mixture of propionic anhydride and xylene and heated under reflux for 15 min in an atmosphere of nitrogen. The gas evolved is led into barium hydroxide solution where precipitation of barium carbonate shows that the ketone has been formed. The excess of anhydride (and solvent) are then distilled off at atmospheric pressure until finally a bath-temperature of 180-200° is recorded. The product is obtained pure by a final vacuum-distillation. 

Subsequent to this work, apoaspartate transaminase was used to assay the stereospecificity of a variety of other transaminases, all of which were shown to involve protonation/deprotonation at the C-4 Si face of the cofactor. These enzymes included pyridoxamine-pyruvate transaminase (EC 2.6.1.30) (26) and a-dialkylamino acid transaminase (27). L-Glutamate decarboxylase (EC 4.1.1.15) catalyzes an abortive transamination reaction when oc-methylglutamate is used as substrate, and this too was shown to occur with protonation at the Si face of C-4 in the intermediate 4d (28) as was the abnormal transamination of D-alanine by serine hydroxymethyltransferase (29). 

Dialkylamino acids, C -dialkylamino acids, amino acids bearing two alkyl substituents at the a-carbon atom. Examples are the naturally occurring amino acids diethylglycine (Deg), a-aminoisobutyric acid (Aib), or isovaline (Iva, 2-amino-2-methylbutyric acid). Such amino acids are often incorporated into peptides to study the conformational requirements of receptors, and are used as building blocks for the stabilization of short peptides in a well-defined conformation, depending on the nature of the two substituents attached to the C -carbon. 3io-Hdices are stabilized by the incorporation of Aib and other C -dialkyl-substituted building blocks [P. Balaram, T. S. Sudha, Int.J. Pept. Protein Res. 1983, 21, 381 I. L. Karle, Biopolymers 1996, 40,157 B. Pispisa et al.. Biopolymers 2000, 53,169]. 

But Still et al. used such a dialkylamino acid ester rearrangement during their elegant synthesis of frallanoHde [124]. They investigated several cyclic allylic esters such as 213 (Scheme 5.2.68). 

Degenkolb, T. and Bruckner, H. (2008) Peptaibiomics Towards a myriad of bioactive peptides containing Ca-dialkylamino acids Chem, Biodivers, 5,1817-1843. 

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