Synthesis of bis-(2,3,4,6-tetra-O-acetyl-α-d-mannopyranosyl)-l-serinyl phosphate, as a prodrug of mannose-1-phosphate

An efficient synthesis of di-mannosyl serinyl phosphate using a convergent strategy involving a silver assisted nucleophilic substitution of tetra-O-acetyl-α-d-mannopyranosyl bromide by a conveniently protected O-serinyl phosphate is described. The straightforward synthesis of phosphoserine under Mitsunobu conditions is also reported.

Figure optionsDownload as PowerPoint slide

2(S)-2-Benzyloxycarbonylamino-3-(di-tert-butoxy-phosphoryloxy)-propionic acid benzyl esterC26H36NO8PDe >95% (by 1H NMR)[α]D20=-6 (c 1.0, CH2Cl2)Source of chirality: N-benzyloxycarbonyl l-serine benzyl ester

2(S)-2-Benzyloxycarbonylamino-3-[bis-(2,3,4,6-tetra-O-acetyl-α-d-mannopyranosyloxy)phosphoryloxy]-propionic acid benzyl esterC46H56NO26PDe >95% (by 1H NMR)[α]D20=+45 (c 1.0, CH2Cl2)Source of chirality: N-benzyloxycarbonyl l-serine benzyl ester and 2,3,4,6-tetra-O-acetyl-α-d-manopyranosyl bromide