Norvaline methyl ester

Ethyl (bornylideneamino)acetate (2) and the imines of (-)-(lf ,2, 5 )-2-hydroxy-3-pinanone and glycine, alanine and norvaline methyl esters were particularly successful as Michael donors. The chiral azaallyl anions, derived from these imines by deprotonation with lithium diisopropylamide in THF at — 80 C, add to various a,/i-unsaturated esters with modest to high diastereoselectivity (see Section 1.5.2.4.2.2.5.). Thus, starting with the imine 2, (R1 = CH,) and ethyl ( )-2-butcnoate, the a,/i-dialkylated glutamate derivative 3 is obtained as a single diastercomer in 90% yield91-92. 

A 40% yield of 5-hydroxy-l-isopropyl-2-methyl-4-propylimidazole (91) has been obtained from the interaction of norvaline methyl ester and N-isopropylacetonitrilium tetrachloroferrate (Scheme 52). 

The interaction with both synthetic and naturally occurring amino acids has been studied extensively glycine (138, 173, 219-221), a-(173, 219) and /3-alanine (138, 220), sarcosine (219), serine (222), aspartic acid (138, 173, 222-226), asparagine (222), threonine (222), proline (219), hydroxyproline (219), glutamic acid (138, 222-225), glutamine (222), valine (219, 227), norvaline (219), methionine (222, 226), histidine (228, 229), isoleucine (219), leucine (219, 230), norleu-cine (219), lysine (222), arginine (222), histidine methyl ester (228), phenylalanine (138, 222), tyrosine (222), 2-amino-3-(3,4-dihydroxy-phenyl jpropanoic acid (DOPA) (222), tryptophan (222), aminoiso-butyric acid (219), 2-aminobutyric acid (219,231), citrulline (222), and ornithine (222). 

Specific activity for L-2-amino butyric acid amide was 9.5U/mg, which was 2.7% that for l-ACL (350U/mg with a substrate concentration of 100 mM). Activities toward alanine amide, threonine amide, norvaline amide, and norleucine amide were all <2.1% that for ACL. The enzyme did not act on a-amino acid, peptides consisting of alanine, or alanine methyl esters. The values for 2-aminobutyramide and alanine amide were both calculated to be 1.0, which identified them as typical racemase-catalyzed reactions [23] ... 

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