23577-92-6

Upstream product

• 540-88-5 acetic acid tert-butyl ester 
• 1499-55-4 2-Amino-pentanedioic acid 5-methyl ester 
• 27025-24-7 Z-D-glutamic γ-methyl ester 
• 115-11-7 isobutene 
• 6893-26-1 D-Glutamic acid 
• 75-65-0 tert-butyl alcohol 
• 501-53-1 benzyl chloroformate 
• 1155-62-0 2-Benzyloxycarbonylamino-pentanedioic acid 
• 4652-65-7 2-Benzyloxycarbonylamino-pentanedioic acid 5-methyl ester 

Downstream Products

• 23736-80-3 N-Benzyloxycarbonyl-α-tert.-butyl-D-glutamyl-α-tert.-butyl-D-glutaminsaeure-pentachlorphenylester 
• 23577-94-8 N-Benzyloxycarbonyl-α-tert.-butyl-D-glutamyl-α-tert.-butyl-D-glutaminsaeure-methylester 
• 170465-61-9 (2R,4R)-4-allyl-2-benzyloxycarbonylamino-pentanedioic acid 1-tert-butyl ester 5-methyl ester 
• 145789-09-9 tri-tert-butyl N--D-glutamate 
• 172793-49-6 tri-tert-butyl N--L-glutamate 
• 172793-51-0 tri-tert-butyl N--N-prop-2-ynylamino>benzoyl>-D-γ-glutamyl>-L-glutamate 
• 145789-11-3 tri-tert-butyl N--N-prop-2-ynylamino>benzoyl>-D-γ-glutamyl>-D-glutamate 
• 20918-72-3 (R)-4-(((benzyloxy)carbonyl)amino)-5-(tert-butoxy)-5-oxopentanoic acid 

Relevant academic research and scientific papers

Quinazoline antifolate thymidylate synthase inhibitors: γ-linked L-D, D- D, and D-L dipeptide analogues of 2-desamino-2-methyl-N10-propargyl-5,8- dideazafolic acid (ICI 198583)

The syntheses of γ-linked L-D, D-D, and D-L dipeptide analogues of 2- desamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (ICI 198583) are described. The general methodology for the synthesis of these molecules involved the preparation of the dipeptide derivatives employing solution phase peptide synthesis followed by condensation of the dipeptide free bases with the appropriate pteroic acid analogue via diethyl cyanophosphoridate (DEPC) activation. In the final step, tert-butyl esters were removed by trifluoroacetic acid (TFA) hydrolysis. Z-L-Glu-OBu(t)-γ-D-Ala-OBu(t), for example, was prepared from α-tert-butyl N-(benzyloxycarbonyl)-L-glutamate and tert-butyl D-alaninate via isobutyl-mixed anhydride coupling. The Z- group was removed by catalytic hydrogenolysis and the resulting dipeptide free base condensed with 2-desamino-2-methyl-N10-propargyl-5,8- dideazapteroic acid via DEPC coupling. Finally, tert-butyl esters were removed by TFA hydrolysis to give ICI 198583-γ-D-Ala. The compounds were tested as inhibitors of thymidylate synthase and L1210 cell growth. Good enzyme and growth inhibitory activity were found with y-linked L-D dipeptides, the best examples being the Glu-γ-D-Glu derivative 35 (K(i) = 0.19 nM, L1210 IC50 = 0.20 ± 0.017 μM) and the Glu-γ-D-α-aminoadipate derivative 39 (K(i) = 0.12 nM, L1210 IC50 = 0.13 ± 0.063 μM). In addition, ICI 198583 L-γ-D-linked dipeptides were resistant to enzymatic degradation in mice.

1-Hydroxy-3-amino-2-piperidone (δ-N-Hydroxycycloornithine) Derivatives: Key Intermediates for the Synthesis of Hydroxamate-Based Siderophores

Several routes for the synthesis of δ-N-(benzyloxy)cycloornithine (2) from glutamic acid derived starting materials are described.Efficient methods were developed for the synthesis of glutamic acid γ-semialdehyde and γ-hydroxynorvaline derivatives as key substrates for the preparation of δ-N-hydroxyornithine analogues.Thus, the best approaches to the synthesis of 2 were: (1) reductive cyclization of an N-hydroxysuccinimide ester of the O-benzyloxime 4 of α-amino-protected glutamic acid γ-semialdehyde 5 and (2) cyclization of the N-(benzyloxy)amide of δ-bromonorvaline (7).