Synthesis of beta-(1-->6)-branched beta-(1-->3) glucohexaose and its analogues containing an alpha-(1-->3) linked bond with antitumor activity.
A beta-(1-->6)-branched beta-(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 alpha-(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 alpha-(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-beta-D-glucopyranoside (27) selectively gave beta-(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 beta-(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 0.5-1mg/kg substantially increased the inhibition of S(180) for CPA, but decreased the toxicity caused by CPA. Some of these oligosaccharides also inhibited U(14) noumenal tumor in mice effectively.
Ning
Jun
J
Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, PO Box 2871, Beijing 100085, PR China. fzkong@mail.rcees.ac.cn
Zhang
Wenhui
W
Yi
Yuetao
Y
Yang
Guangbin
G
Wu
Zhikui
Z
Yi
Jie
J
Kong
Fanzuo
F
D000498:Allyl Compounds / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D002240:Carbohydrate Sequence; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D045744:Cell Line, Tumor; D003520:Cyclophosphamide / Q000494:pharmacology / Q000627:therapeutic use; D006027:Glycosides / Q000737:chemistry; D007912:Lentinan / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000138:chemical synthesis*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000498:Allyl Compounds; D000970:Antineoplastic Agents; D006027:Glycosides; D009844:Oligosaccharides; C472249:glucohexatose; D007912:Lentinan; D003520:Cyclophosphamide