Neoglycopeptide synthesis and purification in multi-gram scale: preparation of O-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-N alpha-fluoren-9-yl-methoxycarbonyl-hydroxyproline and its use in the pilot-scale synthesis of the potent analgesic glycopeptide O1.5-beta-D-galactopyranosyl [DMet2, Hyp5]enkephalinamide.
The preparation of a beta-galactosylated hydroxyproline derivative and its use in the multi-gram solid-phase synthesis of the potent analgesic neoglycopeptide O1.5-beta-D-galactopyranosyl [D-Met2, Hyp5]enkephalinamide is described in this paper. The most closely related impurities have been identified, isolated and characterized. Significant aspects of the synthesis and purification affecting yields and purity of both the building block and the target neoglycopeptide are discussed.
Torres
J L
JL
Unit for Protein Chemistry and Biochemistry, CID - CSIC, Barcelona, Spain. jltqbp@cid.csic.es
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D000701:Analgesics, Opioid / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification*; D004744:Enkephalin, Methionine / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification*; D004745:Enkephalins / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification*; D005697:Galactosides / Q000138:chemical synthesis* / Q000737:chemistry; D006020:Glycopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification*; D006031:Glycosylation; D006909:Hydroxyproline / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D007202:Indicators and Reagents; D010865:Pilot Projects
D000701:Analgesics, Opioid; D004745:Enkephalins; D005697:Galactosides; D006020:Glycopeptides; D007202:Indicators and Reagents; C107577:O-(2,3,4,6-tetra-O-acetyl-galactopyranosyl)-N-fluoren-9-yl-methoxycarbonylhydroxyproline; C060124:enkephalinamide, Met(2)-Hyp(5)galactopyranosyl-; D004744:Enkephalin, Methionine; D006909:Hydroxyproline