Synthesis of phosphites and phosphates of neuraminic acid and their glycosyl donor properties--convenient synthesis of GM3.
The importance and requirements for catalytic activation of sialyl donors are discussed, leading to the acid sensitive phosphite and phosphate moiety, respectively, as leaving group and nitriles as solvent. Therefore, from readily available N-acetylneuraminic acid, derivative 1 with phosphochloridites 2a-f and Huenigs' base sialyl phosphites 3a-f were prepared and isolated in high yields. Oxidation of 3a,c with tert-butyl-hydroperoxide afforded the corresponding phosphates 4a,c. As expected, phosphites 3 could be activated in acetonitrile by catalytic amounts of TMSOTf; thus, from 3a-e as donors and lactose derivatives 8A,B as acceptors the ganglioside building blocks 9A and 9B, respectively, were obtained in good yields. The best results were obtained with diethyl phosphite derivative 3a as sialyl donor, which exceeded by far the results obtained with the corresponding phosphate derivative 4a. Trisaccharide 9B was transformed into known 9A and into the fully O-acetylated GM3-trisaccharide 10.
Martin
T J
TJ
Fakultät Chemie, Universität Konstanz, Germany.
Brescello
R
R
Toepfer
A
A
Schmidt
R R
RR
D002240:Carbohydrate Sequence; D002384:Catalysis; D005679:G(M3) Ganglioside / Q000138:chemical synthesis*; D006031:Glycosylation; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009438:Neuraminic Acids / Q000737:chemistry*; D010710:Phosphates / Q000138:chemical synthesis*; D010757:Phosphorous Acids / Q000138:chemical synthesis*
D005679:G(M3) Ganglioside; D009438:Neuraminic Acids; D010710:Phosphates; D010757:Phosphorous Acids