A new strategy has been developed for GPI glycan-peptide conjugate synthesis based upon a traceless Staudinger reaction between a peptide phosphinothioester and a GPI glycan azide. The strategy was first studied and optimized with simple peptides and GPI glycans, which offered excellent yields of the desired conjugates in both organic and aqueous solvents. It was then used to successfully synthesize an analog of the human CD52 antigen containing the whole CD52 peptide sequence and the conserved trimannose motif of all GPI anchors.

Heparanase cleaves polymeric heparan sulfate (HS) molecules into smaller oligosaccharides, allowing for release of angiogenic growth factors promoting tumor development and autoreactive immune cells to reach the insulin-producing β cells. Interaction of heparanase with HS chains is regulated by specific substrate sulfation sequences. We have synthesized eleven trisaccharides that are highly tunable in structure and sulfation pattern, allowing us to determine how heparanase recognizes HS substrate and selects a favorable cleavage site. Our study shows that ( 1) N-SO 3 − at +1 subsite and 6-O-SO 3 − at −2 subsite of trisaccharides are critical for heparanase recognition; (2) addition of 2-O-SO 3 − at the −1 subsite and of 3-O-SO 3 − to GlcN unit is not advantageous; and (3) the anomeric configuration (α or β) at the reducing end is crucial in controlling heparanase activity. Our study also illustrates that the α-trisaccharide having Nand 6-O-SO 3 − at −2 and +1subsites inhibited heparanase and was resistant toward hydrolysis.

The first total synthesis of a major component of marine glycolipid vesparioside B ( Scheme 1 , 1, R1 = n-C22H45, R2 = n-C14H29) has been accomplished through a convergent [4 + 3] coupling strategy. Key steps included stereoselective installment of a set of challenging 1,2-cis-glycoside bonds. A 2-quinolinecarbonyl-assisted α-galactosylation and a novel β-arabinosylation were developed, respectively, to synthesize the α-galactofuranosidic and the β-arabinopyranosidic linkages. Furthermore, a 4,6-O-benzylidene-controlled α-galactopyranosylation reaction allowed the efficient connection of the left tetrasaccharide donor 2 with the right disaccharide lipid acceptor 3, hence leading to the total synthesis of 1.

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The total synthesis of batatoside L (1), a resin glycoside possessing cytotoxicity against laryngeal carcinoma cells, has been completed in a highly convergent manner. The most crucial step in this total synthesis was the efficient construction of the 18-membered macrolactone framework through the Corey-Nicolaou macrolactonization approach.