190587-50-9

Upstream product

• 147471-66-7 (S)-4-tert-Butoxycarbonylamino-5-ethoxycarbonyloxy-5-oxo-pentanoic acid benzyl ester 
• 66880-77-1 2-tetradecylhexadecanoic acid 
• 190587-51-0 (S)-4-[(R)-2-Amino-3-((2R,3S,4R,5R,6S)-3,4,5-tris-benzyloxy-6-methyl-tetrahydro-pyran-2-yloxy)-propionylamino]-4-methylcarbamoyl-butyric acid benzyl ester 
• 13574-13-5 Boc-Glu(OBzl)-OH 
• 218139-62-9 (R)-2-(2-Tetradecyl-hexadecanoylamino)-3-((2R,3S,4R,5R,6S)-3,4,5-tris-benzyloxy-6-methyl-tetrahydro-pyran-2-yloxy)-propionic acid methyl ester 
• 190586-78-8 N-tert-butoxycarbonyl-D-seryl-L-glutamic acid 1-methylamide 5-benzyl ester 
• 56698-52-3 benzyl N-tert-butyloxycarbonyl-L-γ-glutamate α-N-methylamide 
• 82594-35-2 (S)-4-Amino-4-methylcarbamoyl-butyric acid benzyl ester 

Relevant academic research and scientific papers

Studies on selectin blockers. 7. Structure-activity relationships of sialyl Lewis X mimetics based on modified ser-glu dipeptides

We have previously found that heterochiral fucodipeptides, L-Ser-D-Glu (3a) and D-Ser-L-Glu (3b), exhibited up to 20-100 times more potency than a sialyl Lewis X (sLe(X), 1) and a 3'sulfated Lewis X analogue (2) toward E- selectin binding and have also proposed, from molecular dynamics calculation, that their strong activities would depend on a possible formation of the type II and/or type II' β-turn of compounds 3a,b (Tsukida, T.; Hiramatsu, Y.; Tsujishita, H.; Kiyoi, T.; Yoshida, M.; Kurokawa, K.; Moriyama, H.; Ohmoto, H.; Wada, Y.; Saito, T.; Kondo, H. J. Med. Chem. 1997, 40, 3534-3541). To clarify our hypothesis, we synthesized several analogues of compounds 3a,b and investigated their structure-activity relationships. As a result, it was indicated that the type II and/or type II' β-turn conformation would be a comparatively tight form and would play important roles in favorable binding to E-selectin. These findings indicate that sLe(X) mimetics with type II and type II' β-turn dipeptides could be a useful methodology for the design of an active selectin blocker.

A stereoselective α-fucosylation reaction using 1-hydroxy 2,3,4-trio- benzyl-L-fucose donor for the practical synthesis of selectin blocker

A 1-hydroxy 2,3,4-tri-O-benzyl-L-fucose donor affords a high stereoselectivity of glycosylation in the presence of TMSOTf and is a very useful substrate for the preparation of an α-L-fucosyl dipeptide in a stereoselective manner. The donor will be a key component in the preparation of an attractively biological selectin blocker 1.

Studies on selection blockers. 5. Design, synthesis, and biological profile of sialyl Lewis x mimetics based on modified serine-glutamic acid dipeptides.

We have rationally designed a sLe(x) mimetic based on molecular modeling, synthesized type II and type II' beta-turn dipeptides (3a,b), and evaluated their biological profiles both in vitro and in vivo. Against E-selectin-sLe(x) binding, the type II beta-turn dipeptide L-Ser-D-Glu 3a (IC50, 13 microM) and the type II' beta-turn dipeptide D-Ser-L-Glu 3b (IC50, 5.5 microM) were 20-100-fold more potent blockers than sLe(x) (1; IC50, 600 microM) and a 3'-sulfated Le(x) analog (2; IC50, 280 microM). On the other hand, other stereoisomers, such as L-Ser-L-Glu 3c and D-Ser-D-Glu 3d, were very weak blockers, with IC50 > 1000 microM for both 3c,d. Against the P- and L-selectins, despite much different stereochemistry of compounds 3a-d, the dipeptides 3a-d were all more potent blockers than either sLe(x) or compound 2. Interestingly, compound 3b provided significant in vivo efficacy against an immunoglobulin E-mediated skin reaction in a mouse model. These findings indicate that sLe(x) mimetics with type II and type II' beta-turn dipeptides could be useful in the design of an active selectin blocker in vitro and/or in vivo.