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Synthesis of a Trisaccharide Library by Using a Phenylsulfonate Traceless Linker on Synphase Crowns

✍ Scribed by Takashi Takahashi; Hitoshi Inoue; Yuichi Yamamura; Takayuki Doi


Publisher
John Wiley and Sons
Year
2001
Tongue
English
Weight
124 KB
Volume
113
Category
Article
ISSN
0044-8249

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✦ Synopsis


The development of novel linkers and linkage strategies has become essential in solid-phase synthesis for the discovery of new drugs and materials. In recent years, many efficient linkers were developed. [1] Traceless linkers are advantageous in that the original functional group of the linker does not remain in the product. [2] We have reported a phenylsulfonate traceless linker, [3] which acts as a leaving group under nucleophilic-displacement reaction conditions. [4, 5] With this linker a diversity of products can be obtained, because various functional groups can be introduced at the final stage in a solid-phase synthesis. Herein, we report a high-speed synthesis of a functionalized trisaccharide library utilizing the phenylsulfonate linker on Synphase Crowns. [6, 7] The synthetic strategy is illustrated in Scheme 1. The trisaccharide derivatives I, II, and III which have various functional groups Z at the 6 position of their glucose unit could be synthesized from solid support 4, which consists of a Catalytic synthesis of 5: Imine (0.57 mmol) and acid chloride (0.57 mmol) were combined in 10 mL of CH 3 CN and stirred for 15 min. To this solution was added [Pd 2 (dba) 3 ] Β΄CHCl 3 (5 mol %) in 10 mL of CH 3 CN. The reaction mixture was transferred to a 100 mL reaction bomb and left to stir at room temperature for 30 min. 790 Torr of CO was then added to the reaction mixture, and it was allowed to stir at 55 8C for 24 h. The resulting solution was filtered through celite, redissolved in CHCl 3 , then washed with dilute HCl, saturated aqueous NaHCO 3 , water, and saturated aqueous NaCl, followed by drying over Na 2 SO 4 . After filtration, the solvent was removed in vacuo, and the resultant material dissolved in diethyl ether and cooled to Γ€ 40 8C. The imidazoline 5 was then collected as a white precipitate.


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