SYNTHETIC STUDIES ON SIALOGLYCOCONJUGATES .59. - TOTAL SYNTHESIS OF TUMOR-ASSOCIATED GANGLIOSIDE, SIALYL LE(A)

被引:26
作者
KAMEYAMA, A [1 ]
ISHIDA, H [1 ]
KISO, M [1 ]
HASEGAWA, A [1 ]
机构
[1] GIFU UNIV,DEPT APPL BIOORGAN CHEM,GIFU 50111,JAPAN
关键词
D O I
10.1080/07328309408011671
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The first total synthesis of tumor-associated glycolipid antigen, sialyl Le(a), is described, Methylsulfenyl bromide-silver triflate-promoted coupling of 2-(trimethylsilyl)ethyl O-(2-acetamido-6-O-benzyl-2-deoxy-beta-D-glucopyranosyl)-(1-->3)-O-(2,4,6-tri-O-benzyl-beta-D-galactopyranosyl)-(1-->4)-2,3,6-tri-O-benzyl-beta-D-glucopyranoside (2) with methyl O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha-D-galacto-2-nonulopyranosylonate)-(2-->3)-2,4,6-tri-O-benzoyl-1-thio-beta-D-galactopyranoside (3) afforded the pentasaccharide 4a and 5a in good yields. Glycosylation of 4a with methyl 2,3,4-tri-O-benzyl-1-thio-beta-L-fucopyranoside (6) by use of N-iodosuccinimide (NIS) trifluoromethanesulfonic acid (TfOH) as a promoter, gave the desired hexasaccharide 7. Compound 7 was converted into the alpha-trichloroacetimidate 10, via reductive removal of benzyl groups, O-acetylation, removal of the 2-(trimethylsilyl)ethyl group, and treatment with trichloroacetonitrile, which, on coupling with (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (11), gave the beta-glycoside 12. Finally, 12 was transformed, via selective reduction of the azide group, coupling with octadecanoic acid, O-deacylation, and hydrolysis of the methyl ester group, into the title ganglioside 15 in good yield.
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页码:641 / 654
页数:14
相关论文
共 30 条
[1]  
ADACHI T, 1977, SYNTHESIS-STUTTGART, P45
[2]  
BERG EL, 1991, J BIOL CHEM, V266, P14869
[3]   USE OF SULFENYL HALIDES IN CARBOHYDRATE REACTIONS .1. ALKYL SULFENYL TRIFLATE AS ACTIVATOR IN THE THIOGLYCOSIDE-MEDIATED FORMATION OF BETA-GLYCOSIDIC LINKAGES DURING OLIGOSACCHARIDE SYNTHESIS [J].
DASGUPTA, F ;
GAREGG, PJ .
CARBOHYDRATE RESEARCH, 1988, 177 :C13-C17
[4]  
FUKUSHIMA K, 1990, CANCER RES, V201, P31
[5]  
GAREGG PJ, 1982, CARBOHYD RES, V108, P97
[6]  
HAKOMORI S, 1983, JNCI-J NATL CANCER I, V71, P231
[7]   SELECTIN GMP-140 (CD62, PADGEM) BINDS TO SIALOSYL-LEA AND SIALOSYL-LEX, AND SULFATED GLYCANS MODULATE THIS BINDING [J].
HANDA, K ;
NUDELMAN, ED ;
STROUD, MR ;
SHIOZAWA, T ;
HAKOMORI, S .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1991, 181 (03) :1223-1230
[8]   SYNTHETIC STUDIES ON SIALOGLYCOCONJUGATES .25. REACTIVITY OF GLYCOSYL PROMOTERS IN ALPHA-GLYCOSYLATION OF N-ACETYL-NEURAMINIC ACID WITH THE PRIMARY AND SECONDARY HYDROXYL-GROUPS IN THE SUITABLY PROTECTED GALACTOSE AND LACTOSE DERIVATIVES [J].
HASEGAWA, A ;
NAGAHAMA, T ;
OHKI, H ;
HOTTA, K ;
ISHIDA, H ;
KISO, M .
JOURNAL OF CARBOHYDRATE CHEMISTRY, 1991, 10 (03) :493-498
[9]  
ITAI S, 1991, CANCER, V67, P1576, DOI 10.1002/1097-0142(19910315)67:6<1576::AID-CNCR2820670620>3.0.CO
[10]  
2-2