Synthesis of glycosphingolipids
AssigneeUniversity of Florida Research Foundation, Inc.
InventorsZhongwu Guo, Qingjiang Li
Life of this patent
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Abstract
Provided are methods of synthesizing glycolipids. The methods combine chemical and enzymatic transformations to rapidly provide diverse natural and functionalized glycolipids in a high convergent matter. Stepwise enzymatic elongation of a carbohydrate chain of a common glycolipid precursor, compound (1), provides glycan intermediates of Formula (II), using sugar-nucleotides as glycosyl donors and glycosyltransferases as enzymes. Also provided are glycan intermediates of Formula (II) and alkene intermediates of Formula (IV) and methods of preparing same.
Claims20
A method of synthesizing a glycolipid of Formula (I)
- wherein
- Ra is a C1-30alkylene-A;
- Rb is C1-30alkylene-A′;
- A and A′ are independently H, a fluorescent or molecular tag, or N3;
- each of RC and Rd independently comprise OH or a monosaccharide, disaccharide, trisaccharide, or tetrasaccharide;
- the method comprising
- (a) admixing a glycan intermediate of Formula (II) with an alkene CH═CH—Ra in the presence of Grubbs II catalyst to form an alkene intermediate of Formula (III):
- wherein PN is Boc, Fmoc, Cbz, or Troc, HPN together form Phth, or NHPN together form N3;
- (b) deprotecting the alkene intermediate of Formula (III) to form a deprotected amine, and
- (c) reacting the deprotected amine with Cl—C(O)Rb, RbC(O)—O—C(O)Rb, or HO—C(O) Rb to form the glycolipid of Formula (I).
A glycan intermediate of Formula (II)
- wherein
- each of RC and Rd independently comprise OH or a monosaccharide, disaccharide, trisaccharide, or tetrasaccharide;
- and
- PN is Boc, Fmoc, Troc, or Cbz, HPN together form Phth, or NHPN together form N3;
- with the proviso that when Rd is a monosaccharide or OH and NHPN together form N3, then RC is not OH.
An alkene intermediate of Formula (IV)
- wherein
- Ra is a C10-20alkyl;
- each of RC and Rd independently comprise OH or a monosaccharide, disaccharide, trisaccharide, or tetrasaccharide;
- and
- Re is H, Boc, Fmoc, Troc, or Cbz, HRe together form Phth, or NHRe together form N3;
- with the provisos that when Ra is C13alkyl, RC is OH, and Rd is a monosaccharide, then Re is not H, and when Ra is C13alkyl and Rc and Rd are both OH, then NHRe together are not N3 or NH2.
Dependencies are inferred from the claim text.