403852-37-9

Basic information

• Product Name: methyl N-[(2,3,4-tri-O-acetyl)-β-D-glucopyranuronate-3-nitrobenzyloxycarbonyl]-L-phenylalanyl-L-leucine
• Synonyms: methyl N-[(2,3,4-tri-O-acetyl)-β-D-glucopyranuronate-3-nitrobenzyloxycarbonyl]-L-phenylalanyl-L-leucine
• CAS NO: 403852-37-9
• Molecular Weight: 789.747
• Mol File: 403852-37-9.mol
• Article Data: 1

Chemical Properties

• CAS DataBase Reference: methyl N-[(2,3,4-tri-O-acetyl)-β-D-glucopyranuronate-3-nitrobenzyloxycarbonyl]-L-phenylalanyl-L-leucine(CAS DataBase Reference)
• NIST Chemistry Reference: methyl N-[(2,3,4-tri-O-acetyl)-β-D-glucopyranuronate-3-nitrobenzyloxycarbonyl]-L-phenylalanyl-L-leucine(403852-37-9)
• EPA Substance Registry System: methyl N-[(2,3,4-tri-O-acetyl)-β-D-glucopyranuronate-3-nitrobenzyloxycarbonyl]-L-phenylalanyl-L-leucine(403852-37-9)

Safety Data

• Hazardous Substances Data: 403852-37-9(Hazardous Substances Data)

Upstream product

• 3303-55-7 L-Phe-Leu 
• 148579-95-7 (2S,3S,4S,5R,6S)-3,4,5-Triacetoxy-6-[4-(2,5-dioxo-pyrrolidin-1-yloxycarbonyloxymethyl)-2-nitro-phenoxy]-tetrahydro-pyran-2-carboxylic acid methyl ester 

Downstream Products

• 403852-40-4 methyl N-[β-D-glucopyranuronate-3-nitrobenzyloxycarbonyl]-L-phenylalanyl-L-leucine 

Relevant articles and documents

Synthesis and biological activity of the prodrug of class I major histocompatibility peptide GILGFVFTL activated by β-glucuronidase

The first synthesis of a prodrug of HLA-A2.1 associated antigenic influenza peptide 2a was accomplished. Two methods for synthesis of prodrugs of antigenic peptides activated by β-glucuronidase and comprising a self-immolative 3-nitrobenzyloxycarbonyl moiety were investigated. Reaction of β-glucuronic acid glycoside of 4-hydroxy-3-nitrobenzyl alcohol (3) with N,N′-disuccinimidyl carbonate (DSC) followed by conjugation with AlaOMe, Gly, Thr, Phe-Leu, and Leu-Arg gave carbamates 4a-4f. Deacetylation of 4b and 4e with MeONa/MeOH gave β-glucuronides 5b and 5e. Compound 5e was converted to β-glucuronic acid conjugate 6e by the action of pig liver esterase (PLE). Compound 6e is a substrate for β-glucuronidase. Method of a direct introduction of the prodrug residue into antigenic nonapeptide GILGFVFTL (2b) failed. Alternately, glycine conjugate 5b was activated to pentafluorophenyl ester 10. Model coupling of 10 with Phe-Leu gave tripeptide conjugate ester 11a which was hydrolyzed by PLE to uronic acid 12. Condensation of 10 with octapeptide ILGFVFTL (9) gave prodrug precursor 11b. Octapeptide 9 was prepared by de novo synthesis using a racemization-free fragment coupling method. Ester hydrolysis with Ba(OH)2/MeOH gave the target prodrug 2a which is a substrate for β-glucuronidase. Prodrug 2a does not bind to HLA-A2.1 of T2 human cells defective in major histocompatibility complex I (MHC I)-associated peptide processing. Addition of β-glucuronidase restored the binding to the level observed with parent nonapeptide 2b although higher concentrations of prodrug 2a and enzyme were necessary.