Efficient Synthesis of the Lewis A Tandem Repeat

Abstract

Abstract:The convergent synthesis of the Lewis A (Le a ) tandem repeat is described. The Le a tandem repeat is a carbohydrate ligand for a mannose binding protein that shows potent inhibitory activity against carcinoma growth. The Le a unit,was synthesized by stereoselective nitrile-assisted β-galactosylation with the phenyl 3-O-allyl-2,4,6-tri-O-benzyl-1-thio-β-galactoside, and ether-assisted α-fucosylation with fucosyl (N-phenyl)trifluoroacetimidate. This common Le a unit was easily converted to an acceptor and donor in high yields, and the stereoselective assembly of the hexasaccharide and dodecasaccharide as the Le a tandem repeat framework was achieved by 2-trichloroacetamido-assisted β-glycosylation and the (N-phenyl)trifluoroacetimidate method.

Threshold of Thioglycoside Reactivity Difference Is Critical for Efficient Synthesis of Type I Oligosaccharides by Chemoselective Glycosylation

“…Glycosylations of acceptors 14 and 16 produced the best yields, even though 16 was not the least reactive. Likewise, when the same acceptor was glycosylated with different donors (e.g., acceptor 13 reacting with different donors 6−8; see entries 1, 2, and 9), the reactive donor (8) had the highest yield. Apparently, the presence of two OBn groups at O4 and O6 in GlcNTCA rendered 8 an excellent donor.…”

“…In contrast, chemical synthesis was shown to avoid the disadvantages and additionally to provide these biologically important oligosaccharides in a sufficient quantity with flexibility. Kobayashi et al , for example, recently synthesized the fucosylated oligosaccharide that contained four Le a -tandem repeats by using ( N -phenyl) trifluoroacetimidate donors with a convergent approach. These growing research efforts signify the urgency to produce type I-repeating oligomers.…”

Facile chemoenzymatic synthesis of Lewis a (Lea) antigen in gram-scale and sialyl Lewis a (sLea) antigens containing diverse sialic acid forms

“…Nevertheless, false negative and false positive results are possible and precautions are needed in interpreting the data [7,10,11]. sLe a oligosaccharides and analogs have been synthesized chemically [15][16][17][18][19][20] or chemoenzymatically [21][22][23][24]. Chemoenzymatic synthesis of sLe a antigens by sialidase (e.g.…”

Synthesis of Type-I and Type-II LacNAc-Repeating Oligosaccharides as the Backbones of Tumor-Associated Lewis Antigens

“…The first synthesis of Le a -tandem repeat was developed and reported by Ishida et al. in 2016 ( Scheme 7 ) ( 51 ). The fucose-containing trisaccharide 42 was derived from monosaccharide 41 through multiple protecting group manipulations, followed by two glycosylation steps.…”