Multi-component one-pot synthesis of the tumor-associated carbohydrate antigen Globo-H based on preactivation of thioglycosyl donors.
Two efficient routes for the rapid assembly of the tumor-associated carbohydrate antigen Globo-H hexasaccharide 2 by a preactivation based iterative one-pot strategy are reported. The first method involves the sequential coupling of four glycosyl building blocks, leading to the desired hexasaccharide in 47% overall yield in one-pot synthesis. Although model studies on constructing the challenging Gal-alpha-(1-4)-Gal linkage in Gb3 trisaccharide yielded the desired alpha linkage almost exclusively, a similar approach to assemble the hexasaccharide led to the formation of a significant amount of beta anomer. As an alternative, the second synthesis utilized three components in one pot with the Gal-alpha-(1-4)-Gal linkage preformed, producing the desired hexasaccharide in a similar overall yield as the four component approach. Both methods demonstrate that oligosaccharides containing alpha and beta linkages within the same molecule can be constructed in one pot via a preactivation based approach with higher glyco-assembly efficiencies than the automated solid-phase synthesis strategy. Furthermore, because glycosylations can be carried out independent of anomeric reactivities of donors, it is not necessary to differentiate anomeric reactivities of building blocks through extensive protective group adjustment for chemoselective glycosylation. This confers great flexibilities in the building block design, allowing matching of the donor with the acceptor, leading to improved overall yield.
Wang
Zhen
Z
Department of Chemistry, The University of Toledo, 2801 West Bancroft Street, MS 602, Toledo, Ohio 43606, USA.
Zhou
Luyuan
L
El-Boubbou
Kheireddine
K
Ye
Xin-shan
XS
Huang
Xuefei
X
D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry*; D002240:Carbohydrate Sequence; D006031:Glycosylation; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D021241:Spectrometry, Mass, Electrospray Ionization
D015295:Antigens, Tumor-Associated, Carbohydrate; C472765:Globo-H