Synthesis of β-(1→6)-branched β-(1→3) glucohexaose and its analogues containing an α-(1→3) linked bond with antitumor activity Original Research Article

A β-(1→6)-branched β-(1→3)-glucohexaose, present in many biologically active polysaccharides from traditionally herbal medicines such as Ganoderma lucidum, Schizophyllum commune and Lentinus edodes, was synthesized as its lauryl glycoside 32, and its analogues 18, 20 and 33 containing an α-(1→3) linked bond were synthesized. It is interesting to find that coupling of a 3,6-branched acylated trisaccharide trichloroacetimidate donor 9 with 3,6-branched acceptors 13 and 16 with 3′-OH gave the α-(1→ 3)-linked hexasaccharides 17 and 19, respectively, in spite of the presence of C-2 ester capable of neighboring group participation. However, coupling of 9 with 4-methoxyphenyl 4,6-O-benzylidene-β-d-glucopyranoside (27) selectively gave β-(1→3)-linked tetrasaccharide 28. Simple chemical transformation of the tetrasaccharide 28 gave acylated tetrasaccharide trichloroacetimidate 29. Coupling of 29 with lauryl (1→6)-linked disaccharide 26 with 3-OH gave β-(1→3)-linked hexasaccharide 30 as the major product. Bioassay showed that in combination with the chemotherapeutic agent cyclophospamide (CPA), the hexaose 18 at a dose of 0.5–1 mg/kg substantially increased the inhibition of S180 for CPA, but decreased the toxicity caused by CPA. Some of these oligosaccharides also inhibited U14 noumenal tumor in mice effectively.