313054-59-0Relevant articles and documents
Synthesis of N-propargyl iminosugar scaffolds for compound library generation using click chemistry
Wilkinson, Brendan L.,Bornaghi, Laurent F.,Lopez, Marie,Healy, Peter C.,Poulsen, Sally-Ann,Houston, Todd A.
scheme or table, p. 821 - 829 (2011/08/03)
We have developed an efficient synthesis of N-propargyl iminosugars for use in diversity-oriented library development. Through a common, crystalline intermediate both piperidine and azepane scaffolds can be prepared with an alkyne functional group, allowi
Synthesis of 4-substituted phenyl 2,5-anhydro-1,6-dithio-α-D-gluco- and -α-L-guloseptanosides possessing antithrombotic activity
Bozo, Eva,Medgyes, Adel,Boros, Sandor,Kuszmann, Janos
, p. 25 - 40 (2007/10/03)
Two independent approaches were investigated for the synthesis of 3,4-di-O-acetyl-1,6:2,5-dianhydro-1-thio-D-glucitol (18), a key intermediate in the synthesis of 1,3,4-tri-O-acetyl-2,5-anhydro-6-thio-α-D-glucoseptanose (13), needed as glycosyl donor. In the first approach 1,6-dibromo-1,6-dideoxy-D-mannitol was used as starting material and was converted via 2,5-anhydro-1,6-dibromo-1,6-dideoxy-4-O-methanesulfonyl-3-O-tetra hydropyranyl-D-glucitol into 18. The second approach started from 1,2:5,6-di-O-isopropylidene-D-mannitol and the allyl, 4-methoxybenzyl as well as the methoxyethoxymethyl groups were used, respectively, for the protection of the 3,4-OH groups. The resulting intermediates were converted via their 1,2:5,6-dianhydro derivatives into the corresponding 3,4-O-protected 2,5-anhydro-6-bromo-6-deoxy-D-glucitol derivatives. The 1,6-thioanhydro bridge was introduced into these compounds by exchanging the bromine with thioacetate, activating OH-1 by mesylation and treating these esters with sodium methoxide. Among these approaches, the 4-methoxybenzyl protection proved to be the most suitable for a large scale preparation of 18. Pummerer rearrangement of the sulfoxide, obtained via oxidation of 18 gave a 1:9 mixture of 1,3,4-tri-O-acetyl-2,5-anhydro-6-thio-α-L-gulo- (12) and -D-glucoseptanose 13. When 12 or 13 were used as donors and trimethylsilyl triflate as promoter for the glycosylation of 4-cyanobenzenethiol, a mixture of 4-cyanophenyl 3,4-di-O-acetyl-2,5-anhydro-1,6-dithio-α-L-gulo- (58) and -α-D-glucoseptanoside (61) was formed suggesting an isomerisation of the heteroallylic system of the intermediate. A similar mixture of 58 and 61 resulted when 18 was treated with N-chloro succinimide and the mixture of chlorides was used in the presence of zinc oxide for the condensation with 4-cyanobenzenethiol. When 4-nitrobenzenethiol was applied as aglycon and boron trifluoride etherate as promoter, a mixture of 4-nitrophenyl 3,4-di-O-acetyl-2,5-anhydro-1,6-dithio-α-L-gulo- (60) and -α-D-glucoseptanoside (62) was obtained. Deacetylation of 58, 61 and 62 according to Zemplen afforded 4-cyanophenyl 2,5-anhydro-1,6-dithio-α-L-guloseptanoside (59), 4-cyanophenyl 2,5-anhydro-1,6-dithio-α-D-glucoseptanoside (63) and 4-nitrophenyl 2,5-anhydro-1,6-dithio-α-D-glucoseptanoside (66), respectively. The 4-cyano group of 63 was transformed into the 4-aminothiocarbonyl, and the 4-(methylthio)(imino)methyl derivative and the 4-nitro group of 66 into the acetamido derivative. All of these thioglycosides displayed a stronger oral antithrombotic effect in rats compared with beciparcil, used as reference. (C) 2000 Elsevier Science Ltd.
