98302-79-5

Upstream product

• 97443-89-5 (2S,5S)-1-benzoyl-2-(tert-butyl)-3-methyl-5-(3'-thiabutyl)imidazolidin-4-one 
• 103024-71-1 N-acetyl-2-methyl-D-methionine 
• 98262-63-6 (2R,5R)-1-benzoyl-2-(tert-butyl)-3,5-dimethyl-5-(3'-thiabutyl)imidazolidin-4-one 
• 121703-94-4 N-Chloroacetyl-α-methylmethionine 

Relevant academic research and scientific papers

Heterocyclic inhibitors of farnesyl protein transferase

Inhibition of farnesyl protein transferase is effected by compounds of the formula its enantiomers, diastereomers, pharmaceutically acceptable salts, prodrugs or solvates thereof, wherein:, A1 and A2 are each independently H, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, phenyl or substituted phenyl;, G1 is S or O;, G2 is H, -C(O)OH, -C(O)NH2, 5-tetrazolyl, -C(O)N(R7)OH or -CH2OH;, X is O or R8N;, Y and Z are each independently -CH2- or -C(O)-;, R1, R2, R3, R4, R5, R6 and R7 are each independently H or alkyl;, R1 may also be alkanoyl, R1 and A1 taken together may be -(CH2)m;, R8 is H, alkyl, phenyl, phenylalkyl, substituted phenyl, (substituted phenyl)alkyl or -C(O)R9;, R9 is H, alkyl, phenyl, phenylalkyl, substituted phenyl or (substituted phenyl)alkyl;, m is 3 or 4;, n is 0, 1 or 2;, p is 0, 1 or 2; and, q is 0 or 1, with the proviso that when p is 0, then q is also 0.

Kinetic Resolution of Unnatural and Rarely Occuring Amino Acids: Enantioselective Hydrolysis of N-Acyl Amino Acids Catalyzed by Acylase I

Acylase I (aminoacylase; N-acylamino-acid amidohydrolase, EC 3.5.1.14, from porcine kidney and the fungus Aspergillus) is broadly applicable enzymatic catalyst for the kinetic resolution of unnatural and rarely occuring α-amino acids.Its enantioselectivity for the hydrolysis of N-acyl L-α-amino acids is nearly absolute, yet it accepts substrates having a wide range of structure and functionality.This paper reports the initial rates of enzyme-catalyzed hydrolysis of over 50 N-acyl amino acids and analogues, the stabilities of the enzymes in aqueous and aqueous/organic solutions, and the effects of different acyl groups and metal ions on the rates of enzymatic hydrolysis.Eleven α-amino and α-methyl α-amino acids were resolved on a 2-29-g scale.Crude L- and D-amino acid products had generally >90percent ee.The utility of resolved amino acids as chiral synthons was illustrated by the preparation of (R)- and (S)-1-butene oxide and the diastereoselective (cis:trans, 7-8:1) iodolactonization of three 2-amino-4-alkenoic acid derivatives.

α-Alkylation of Amino Acids without Racemization. Preparation of Either (S)- or (R)-α-Methyldopa from (S)-Alanine

Enantiomerically pure cis- and trans-5-alkyl-1-benzoyl-2-(tert-butyl)-3-methylimidazolidin-4-ones (1, 2, 11, 15, 16) and trans-2-(tert-butyl)-3-methyl-5-phenylimidazolidin-4-one (20), readily available from (S)-alanine, (S)-valine, (S)-methionine, and (R)-phenylglycine are deprotonated to chiral enolates (cf. 3, 4, 12, 21).Diastereoselective alkylation of these enolates to 5,5-dialkyl- or 5-alkyl-5-arylimidazolidinones (5, 6, 9, 10, 13a-d, 17, 18, 22) and hydrolysis give α-alkyl-α-amino acids such as (R)- and (S)-α-methyldopa (7 and 8a, resp.), (S)-α-methylvaline (14), and (R)-α-methyl-methionine (19).The configuration of the products is proved by chemical correlation and by NOE 1H-NMR measurements (see 23, 24).In the overall process, a simple, enantiomerically pure α-amino acid can be α-alkylated with retention or with inversion of configuration through pivalaldehyde acetal derivatives.Since no chiral auxiliary is required, the process is coined 'self-reproduction of a center of chirality'.The method is compared with other α-alkylations of amino acids occuring without racemization.The importance of enantiomerically pure, α-branched α-amino acids as synthetic intermediates and for the preparation of biologically active compounds is discussed.