202477-59-6Relevant articles and documents
Design and synthesis of galactose-conjugated fluorinated and non-fluorinated proline oligomers: Towards antifreeze molecules
Sumii, Yuji,Hibino, Hayata,Saidalimu, Ibrayim,Kawahara, Hidehisa,Shibata, Norio
supporting information, p. 9749 - 9752 (2018/09/10)
Galactose-conjugated fluorinated and non-fluorinated proline oligomers that exhibit an α-helical structure with hydrophilic and lipophilic parts were designed as potential antifreeze molecules. These galactose-proline oligomers were synthesized and their physical properties were evaluated. Interestingly, the non-fluorinated galactose-proline oligomers showed in contrast to the fluorinated analogues weak antifreeze activity. The difference in antifreeze activity should be attributed to the fluorine gauche effect, which should induce a conformation in fluorinated prolines that is different from that of natural proline. The results obtained in this study thus suggest that the 3D conformation of the galactose-conjugated fluorinated and non-fluorinated proline oligomers is very important for their anti-freezing properties.
Efficient large-scale synthesis of BILN 2061, a potent HCV protease inhibitor, by a convergent approach based on ring-closing metathesis
Yee, Nathan K.,Farina, Vittorio,Houpis, Ioannis N.,Haddad, Nizar,Frutos, Rogelio P.,Gallou, Fabrice,Wang, Xiao-Jun,Wei, Xudong,Simpson, Robert D.,Feng, Xuwu,Fuchs, Victor,Xu, Yibo,Tan, Jonathan,Zhang, Li,Xu, Jinghua,Smith-Keenan, Lana L.,Vitous, Jana,Ridges, Michael D.,Spinelli, Earl M.,Johnson, Michael,Donsbach, Kai,Nicola, Thomas,Brenner, Michael,Winter, Eric,Kreye, Paul,Samstag, Wendelin
, p. 7133 - 7145 (2007/10/03)
A multistep scalable synthesis of the clinically important hepatitis C virus (HCV) protease inhibitor BILN 2061 (1) is described. The synthesis is highly convergent and consists of two amide bond formations, one etherification, and one ring-closing metath
Technical scale synthesis of a new and highly potent thrombin inhibitor
Bernard, Harald,Buelow, Gerd,Lange, Udo E. W.,Mack, Helmut,Pfeiffer, Thomas,Schaefer, Bernd,Seitz, Werner,Zierke, Thomas
, p. 2367 - 2375 (2007/10/03)
In this account, we describe the development of an efficient and convergent process for the peptidomimetic thrombin inhibitor 1 on production plant scale. Starting from nicotinonitrile (13), (2S,4R)-1-(tert-butoxycarbonyl)-4-hydroxy-2- pyrrolidinecarboxylic acid (5) and (2R)-2-amino-3-cyclohexylpropanoic acid (29) compound 1 was obtained in 16 chemical steps. New methods had been developed for the preparation of the key intermediate dehydroproline 22 and the transformation of nitriles into amidines. The thrombin inhibitor 1 was isolated by special techniques (nanofiltration and spray drying). Almost all salts of 1 are amorphous, however, a crystalline complex was obtained with 1,2-benzisothiazol-3(2H)-one 1,1-dioxide (Saccharin).