Linear synthesis of a protected H-type II pentasaccharide using glycosyl phosphate building blocks.
A linear synthesis of a fully protected H-type II blood group determinant pentasaccharide utilizing glycosyl phosphate and glycosyl trichloroacetimidate building blocks is reported. Envisioning an automated solid-phase synthesis of blood group determinants, the utility of glycosyl phosphates in the stepwise construction of complex oligosaccharides, such as the H-type II antigen, is demonstrated. Installation of the central glucosamine building block required the screening of a variety of nitrogen protecting groups to ensure good glucosamine donor reactivity and protecting group compatibility. The challenge to differentiate C2 of the terminal galactose in the presence of other hydroxyl and amine protecting groups prompted us to introduce the 2-(azidomethyl)benzoyl group as a novel mode of protection for carbohydrate synthesis. The compatibility of this group with traditionally employed protecting groups was examined, as well as its use as a C2 stereodirecting group in glycosylations. The application of the 2-(azidomethyl)benzoyl group along with a systematic evaluation of glycosyl donors allowed for the completion of the pentasaccharide and provides a synthetic strategy that is expected to be generally amenable to the solid support synthesis of blood group determinants.
Love
K R
KR
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Andrade
R B
RB
Seeberger
P H
PH
D000017:ABO Blood-Group System / Q000737:chemistry*; D015703:Antigens, CD / Q000737:chemistry*; D002240:Carbohydrate Sequence; D006031:Glycosylation; D006801:Humans; D007983:Lewis Blood Group Antigens / Q000737:chemistry; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000138:chemical synthesis*; D013403:Sugar Phosphates / Q000737:chemistry
D000017:ABO Blood-Group System; D015703:Antigens, CD; D007983:Lewis Blood Group Antigens; D009844:Oligosaccharides; D013403:Sugar Phosphates