Stereoselective direct glycosylation with anomeric hydroxy sugars by activation with phthalic anhydride and trifluoromethanesulfonic anhydride involving glycosyl phthalate intermediates.
An efficient direct one-pot glycosylation method with anomeric hydroxy sugars as glycosyl donors employing phthalic anhydride and triflic anhydride as activating agents has been developed. Thus, highly stereoselective beta-mannopyranosylations were achieved by the reaction of 2,3-di-O-benzyl-4,6-O-benzylidene-D-mannopyranose (2) with phthalic anhydride in the presence of DBU at room temperature followed by sequential addition of DTBMP and Tf2O and glycosyl acceptors to the reaction mixture at -78 degrees C in one-pot. Stereoselective alpha-glucopyranosylations with 2,3-di-O-benzyl-4,6-O-benzylidene-D-glucopyranose (25) and other glycosylations with glucopyranoses and mannopyranoses having tetra-O-benzyl- and tetra-O-benzoyl protecting groups were also possible by utilizing the present one-pot glycosylation protocol. The possible mechanism for the beta-mannosylation with 2 was proposed based on the NMR study, in which alpha-mannosyl phthalate 55alpha and alpha-mannosyl triflate 59 were detected as intermediates. The versatility and efficiency of the present glycosylation methodology, especially those of the beta-mannopyranosylation protocol, were readily demonstrated by the efficient synthesis of protected beta-(1-->4)-D-mannotriose 62 and beta-(1-->4)-D-mannotetraose 67 with perfect beta-stereoselectivity.
Center for Bioactive Molecular Hybrids and the Department of Chemistry, Yonsei University, Seoul 120-749, Korea. kwan@yonsei.ac.kr
Kwan Soo
KS
Kim
Dinanath Baburao
DB
Fulse
Ju Yuel
JY
Baek
Bo-Young
BY
Lee
Heung Bae
HB
Jeon
D000812:Anhydrides; D002241:Carbohydrates / Q000737:chemistry*; D006031:Glycosylation; D008362:Mannosides / Q000737:chemistry*; D009844:Oligosaccharides / Q000138:chemical synthesis*; D010795:Phthalic Acids; D010796:Phthalic Anhydrides; D013237:Stereoisomerism
D000812:Anhydrides; D002241:Carbohydrates; D008362:Mannosides; D009844:Oligosaccharides; D010795:Phthalic Acids; D010796:Phthalic Anhydrides; C032279:phthalic acid; C043103:phthalic anhydride