Synthesis of sulfated octadecyl ribo-oligosaccharides with potent anti-AIDS virus activity by ring-opening polymerization of a 1,4-anhydroribose derivative

被引:16
作者
Choi, Y
Yoshida, T
Mimura, T
Kaneko, Y
Nakashima, H
Yamamoto, N
Uryu, T
机构
[1] HOKKAIDO UNIV, GRAD SCH SCI, DIV BIOL SCI, KITA KU, SAPPORO, HOKKAIDO 060, JAPAN
[2] UNIV TOKYO, INST IND SCI, MINATO KU, TOKYO 106, JAPAN
[3] AJINOMOTO CO INC, CHUO KU, TOKYO 108, JAPAN
[4] YAMANASHI MED UNIV, SCH MED, YAMANASHI 40938, JAPAN
[5] TOKYO MED & DENT UNIV, SCH MED, BUNKYO KU, TOKYO 113, JAPAN
关键词
ring-opening polymerization; oligosaccharide; sulfated alkyl ribofuranan; anti-AIDS virus activity; high resolution NMR;
D O I
10.1016/0008-6215(95)00372-X
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 synthesis and anti-AIDS virus activity of sulfated octadecyl ribofuranans with medium-range molecular weights have been investigated. Selective ring-opening polymerization of 1,4-anhydro-2,3-di-O-benzyl-alpha-D-ribopyranose with 10-20 mol% of boron trifluoride etherate as a catalyst in a large amount of dichloromethane gave 2,3-di-O-benzyl-(1-->5)-alpha-D-ribofuranan in good yield. The molecular weight of the benzylated ribofuranan was in the range of 9 X 10(3) to 10 X 10(3). Debenzylation of the polymer followed by acetylation gave peracetylated (1-->5)-alpha-D-ribofuranans. The peracetylated ribofuranans were treated with octadecyl alcohol and a stannic chloride catalyst to afford acetylated ribofuranans having octadecyl groups at the reducing terminal. The molecular weights of the resulting acetylated octadecyl ribofuranans were below 9 X 10(3). Sulfation of the deacetylated octadecyl ribofuranans by piperidine-N-sulfonic acid in dry Me(2)SO gave sulfated octadecyl ribofuranans with molecular weights of 3 X 10(3) to 9 X 10(3) and sulfur contents of 13.0-16.2%. The sulfated octadecyl ribofuranans had potent anti-AIDS virus activity, EC(50) = 0.6-2.5 mu g/mL (a standard curdlan sulfate showed EC(50) = 0.43 mu g/mL), and low anticoagulant activity, 4-17 units/mg (a standard dextran sulfate, 22.7 unit/mg). Structural analysis of the ribofuranans was performed by NMR at 400 and 600 MHz.
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页码:113 / 123
页数:11
相关论文
共 17 条
[11]   SELECTIVE RING-OPENING POLYMERIZATION OF 1,4-ANHYDRO-ALPHA-D-RIBOPYRANOSE DERIVATIVES AND SYNTHESIS OF STEREOREGULAR (1-4)-BETA-D-RIBOPYRANAN [J].
URYU, T ;
KITANO, K ;
ITO, K ;
YAMANOUCHI, J ;
MATSUZAKI, K .
MACROMOLECULES, 1981, 14 (01) :1-9
[12]   ARTIFICIAL POLYSACCHARIDES AND THEIR BIOLOGICAL-ACTIVITIES [J].
URYU, T .
PROGRESS IN POLYMER SCIENCE, 1993, 18 (04) :717-761
[13]  
Uryu T., 1990, MODELS BIOPOLYMERS R, P133
[14]  
*US PHARM NAT FORM, 1985, USP 21
[15]   SYNTHESIS AND STRUCTURAL-ANALYSIS OF CURDLAN SULFATE WITH A POTENT INHIBITORY EFFECT INVITRO OF AIDS VIRUS-INFECTION [J].
YOSHIDA, T ;
HATANAKA, K ;
URYU, T ;
KANEKO, Y ;
SUZUKI, E ;
MIYANO, H ;
MIMURA, T ;
YOSHIDA, O ;
YAMAMOTO, N .
MACROMOLECULES, 1990, 23 (16) :3717-3722
[16]   SYNTHESIS OF BRANCHED RIBOFURANANS AND THEIR SULFATES WITH STRONG ANTI-AIDS VIRUS ACTIVITY BY SELECTIVE RING-OPENING COPOLYMERIZATION OF 1,4-ANHYDRO-ALPHA-D-RIBOPYRANOSE DERIVATIVES [J].
YOSHIDA, T ;
KATAYAMA, Y ;
INOUE, S ;
URYU, T .
MACROMOLECULES, 1992, 25 (16) :4051-4057
[17]   SYNTHESIS OF CELLULOSE-TYPE POLYRIBOSES AND THEIR BRANCHED SULFATES WITH ANTI-AIDS VIRUS ACTIVITY BY SELECTIVE RING-OPENING COPOLYMERIZATION OF 1,4-ANHYDRO-ALPHA-D-RIBOPYRANOSE DERIVATIVES [J].
YOSHIDA, T ;
WU, CP ;
SONG, LX ;
URYU, T ;
KANEKO, Y ;
MIMURA, T ;
NAKASHIMA, H ;
YAMAMOTO, N .
MACROMOLECULES, 1994, 27 (16) :4422-4428