Synthesis of asialo GM1.: New insights in the application of sulfonamidoglycosylation in oligosaccharide assembly:: Subtle proximity effects in the stereochemical governance of glycosidation

被引:38
作者
Kwon, O
Danishefsky, SJ
机构
[1] Columbia Univ, Dept Chem, New York, NY 10027 USA
[2] Sloan Kettering Inst Canc Res, Bioorgan Chem Lab, New York, NY 10021 USA
关键词
D O I
10.1021/ja9724957
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The total synthesis of asialo GM(1) (1a) has been accomplished, Using related chemistry, the methyl glycoside of the asialo compound (1b) has also been synthesized. These kinds of compounds have been identified as potential ligands for bacterial and viral infection sites, A simpler structure, which hits also been identified for its infection attracting structure in the context of glycopeptides and glycolipids (methyl glycoside 2), has also been synthesized. The key common phase in the syntheses involves the sulfonamidoglycosidation reaction which is used to create a beta-linkage leading to a galNAc residue joined to the C-4 hydroxyl group of a galactose unit either as a monosaccharide (see compound 2) or as C-4' in the contest of a lactosyl moiety, During the course of these studies there was encountered an unusual "proximal hydroxyl" directing effect. Thus, when C-4 on the galactose ring of an azaglycosylating donor bears a free hydroxyl (see, for instance, compound 13), beta-glycoside formation predominates. When this hydroxyl group is blocked, the process tends in the direction of alpha-glycoside formation (see compound 32), These findings were explained as arising from a critical intramolecular hydrogen bond between the C-4 axial hydroxyl of the galactose donor and its proximal pyranosidal ring oxygen. This interaction stabilizes conformations from which beta-glycosidation predominates.
引用
收藏
页码:1588 / 1599
页数:12
相关论文
共 29 条
[1]   STUDY OF AN INTRAMOLECULAR, BIFURCATED HYDROGEN-BOND IN 1,3-DIOXAN-5-OL BY MICROWAVE SPECTROSCOPY [J].
ALONSO, JL ;
WILSON, EB .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1980, 102 (04) :1248-1251
[2]   DEFECTIVE ACIDIFICATION OF INTRACELLULAR ORGANELLES IN CYSTIC-FIBROSIS [J].
BARASCH, J ;
KISS, B ;
PRINCE, A ;
SAIMAN, L ;
GRUENERT, D ;
ALAWQATI, Q .
NATURE, 1991, 352 (6330) :70-73
[3]  
BARASCH J, 1993, J CELL SCI, P229
[4]  
BERRESI F, 1996, J CARBOHYD CHEM, V14, P1043
[5]   TOTAL SYNTHESIS OF A HUMAN BREAST-TUMOR ASSOCIATED ANTIGEN [J].
BILODEAU, MT ;
PARK, TK ;
HU, SH ;
RANDOLPH, JT ;
DANISHEFSKY, SJ ;
LIVINGSTON, PO ;
ZHANG, SL .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1995, 117 (29) :7840-7841
[6]   RECEPTOR SPECIFICITY OF ADHERENCE OF STREPTOCOCCUS-PNEUMONIAE TO HUMAN TYPE-II PNEUMOCYTES AND VASCULAR ENDOTHELIAL-CELLS IN-VITRO [J].
CUNDELL, DR ;
TUOMANEN, EI .
MICROBIAL PATHOGENESIS, 1994, 17 (06) :361-374
[7]   APPLICATION OF THE GLYCAL ASSEMBLY METHOD TO THE CONCISE SYNTHESIS OF NEOGLYCOCONJUGATES OF LE(Y) AND LE(B) BLOOD-GROUP DETERMINANTS AND OF H-TYPE-I AND H-TYPE-II OLIGOSACCHARIDES [J].
DANISHEFSKY, SJ ;
BEHAR, V ;
RANDOLPH, JT ;
LLOYD, KO .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1995, 117 (21) :5701-5711
[8]   Glycals in organic synthesis: The evolution of comprehensive strategies for the assembly of oligosaccharides and glycoconjugates of biological consequence [J].
Danishefsky, SJ ;
Bilodeau, MT .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION IN ENGLISH, 1996, 35 (13-14) :1380-1419
[9]   REGIOSELECTIVE MANIPULATION OF HYDROXYL-GROUPS VIA ORGANOTIN DERIVATIVES [J].
DAVID, S ;
HANESSIAN, S .
TETRAHEDRON, 1985, 41 (04) :643-663
[10]  
GASA S, 1983, J LIPID RES, V24, P174