Nonproteinogenous amino acids

Formation of functionalized cyclic nitrones via a new reaction intermediate, nitrosoketene, and its development for the synthesis of nonproteinogenic amino acids 99YGK116. 

Introduction of Nonproteinogenic Amino Acids - Toward More Selective, Stable, and Easily Handled Biocatalysts... 

Nutrient availability also plays a major role in exudation, with deficiencies in N, P, or K often increasing the rate of exudation (218). It is believed that nutrient deficiency may trigger the release of substances such as organic acids or nonproteinogenic amino acids (phytosiderophores), which may enhance the acquisition of the limiting nutrient (219,220). An example here might be the release of phenolic acids such as caffeic acid in response to iron deficiency, which results in an increase in uptake of the cation (221). 

Antibiotic effects of nonprotein amino acids have not been studied in much detail with soil microorganisms. The organs of legumes alone contain more than 300 nonproteinogenic amino acids, such as methylene-glutamine, common to all... 

Schollkopf, U. Enantioselective Synthesis of Nonproteinogenic Amino Acids. 109, 65-84 (1983). 

Particularly important to the pathways of modular synthases is the incorporation of novel precursors, including nonproteinogenic amino acids in NRP systems [17] and unique CoA thioesters in PK and fatty acid synthases [18]. These building blocks expand the primary metabolism and offer practically unlimited variability applied to natural products. Noteworthy within this context is the contiguous placement of biosynthetic genes for novel precursors within the biosynthetic gene cluster in prokaryotes. Such placement has allowed relatively facile elucidation of biosynthetic pathways and rapid discovery of novel enzyme mechanisms to create such unique building blocks. These new pathways offer a continued expansion of the enzymatic toolbox available for chemical catalysis. 

In the search of new methodologies for the asymmetric synthesis of nonproteinogenic amino acids, 8-methyl-4,8a-diphenyltetrahydro-17/-pyrrolo[2.1 -r l, 4 oxazinc-l, 6(7//)-dionc 62, obtained as described in Scheme 24 (Section 11.11.7.3), was selectively reduced at the lactam carbonyl with BH3 and further opened by hydrogenolysis to give syn-disubstituted proline derivative 64 in 95% yield <1997SL935> (Scheme 6). It is noteworthy that hydrogenolysis did not affect the benzylic position of bicyclic compound 63. 

The present chapter focuses on specific aspects of these challenges, namely peptide bond hydrolysis (chemical and enzymatic) and intramolecular reactions of cyclization-elimination (Fig. 6.4). This will be achieved by considering, in turn a) the enzymatic hydrolysis of prodrugs containing a peptide pro-moiety (Sect. 6.2), b) the chemical hydrolysis of peptides (Sect. 6.3), c) the enzymatic hydrolysis of peptides containing only common amino acids (Sect. 6.4), d) the hydrolysis of peptides containing nonproteinogenic amino acids (Sect. 6.5), and, finally, e) the hydrolysis of peptoids, pseudopeptides and peptidomimetics (Sect. 6.6). 

Structure and Function of Peptidyl Carrier Protein Domains Structure and Function of Adenylation Domains Structure and Function of Condensation Domains Structure and Function of Thioesterase Domains Multidomain NRPS Structural Information PCP-C didomain structure PCP-TE didomain structure Structure of a C-A-PCP-TE termination module Pathways to Nonproteinogenic Amino Acids Incorporated into NRP Natural Nonproteinogenic Amino Acids Present as Cellular Metabolites Modification of Proteinogenic Amino Acids Nonproteinogenic Amino Acids Derived from Multistep Pathways Tailoring Enzymology in NRP Natural Products Chemical Approaches Toward Mechanistic Probes and Inhibitors of NRPS... 

Pathways to Nonproteinogenic Amino Acids incorporated into NRP Naturai Products... 

Nonproteinogenic Amino Acids Present as Cellular Metabolites... 

Enzymatic elaboration of proteinogenic amino acids is the most common pathway to nonproteinogenic amino acids. Six representative examples are illustrated in Figure 14(b). Amino acids that have undergone oxidation... 

Figure 14 Summary of pathways (a-c) to nonproteinogenic amino acids found in NRP natural products.

Nonproteinogenic Amino Acids Derived from Multistep Pathways... 

Figure 15 Use of NRPS enzymology in the biosynthetic pathways to nonproteinogenic amino acids. R signifies a nonproteinogenic side chain.

Schollkopf, U. Enantioselective Synthesis of Nonproteinogenic Amino Acids. 109, 65-84 (1983). Shibata, M. Modern Syntheses of Cobalt(III) Complexes. 110, 1-120 (1983). ... 

Finally, a variety of almost enantiomerically pure, nonproteinogenic amino acids are obtainable from metalation and low temperature alkylation of 2,5-dialkoxy-3,6-dihydropyrazines (see Section 1.1.1.4.6.). 

The bis-lactimether method is a very versatile and useful method of preparing a large variety of nonproteinogenic amino acids in high yields and with excellent enantioselectivities (>95%)1 5. The method is based on the metalation of 3,6-dialkoxy-2,5-dihydropyrazines (bis-lactimethers 1) with strong bases (in general, butyllithium) and subsequent alkylation with electrophiles. The reaction product 2 can be hydrolyzed under mild acidic conditions to give the desired a-amino esters 3, which can be converted to the free amino acids. 

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