Synthesis and Biological Activities of Lipid A Analogs : Modification of a Glycosidically Bound Group with Chemically Stable Polar Acidic Groups and Lipophilic Groups on the Disaccharide Backbone with Tetradecanoyl or N-Dodecanoylglycyl Groups

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概要

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• Six novel lipid A analogs were synthesized. The first two analogs, 4 and 5,have an α-glycosidically bound carboxymethyl or 1,3-dicarboxyisopropyl group on the disaccharide backbone with four tetradecanoyl groups. The next three analogs, 6,7 and 8,have two or four N-dodecanoylglycyl groups on the 1-α-O-phosphonooxyethylated disaccharide backbone. Analog 6 bears N-dodecanoylglycyl groups on the hydroxyl functions at positions 3 and 3', and tetradecanoyl groups on the amino functions at positions 2 and 2'. Analog 7 is a 2,3,2' and 3'-tetrakis(N-dodecanoylglycyl) derivative, and analog 8 resembles compound 6,but the binding of the N-dodecanoylglycyl and tetradecanoyl groups at positions 2,2' and 3,3' are reversed. The third analog, 9,has the same acyl group conflguration as compound 6,but has a 1,3-dicarboxyisopropyl group at position C-1. Compounds 4 and 5 exhibited definite antitumor activity against Meth A fibrosarcoma, indicating that the phosphate group at the C-1 position in lipid A could be replaced by the carboxylic acid without reducing the antitumor activity. In rabbits, compounds 6 and 9 exhibited potent antitumor activity, but their toxicity was extremely low. On the other hand, compounds 7 and 8 showed no antitumor activity. The levels of antitumor activity of 6 and 9 were similar to those of the natural-type lipid A. The antitumor activities of analogs with a N-dodecanoyglycyl group on the disaccharide backbone depended on the connecting sites of the acyl groups.

• 社団法人日本薬学会の論文
• 1991-12-25

著者

• 日馬 恒雄

  Exploratory Research Laboratories I Daiichi Pharmaceutical Co. Ltd.

• 長田 恭明

  Exploratory Research Laboratories I, Daiichi Pharmaceutical Co., Ltd.,

• 熊澤 栄治

  Exploratory Research Laboratories I Daiichi Pharmaceutical Co. Ltd.

• 小野 承行

  Exploratory Research Laboratories I Daiichi Pharmaceutical Co. Ltd.

• 中山 清

  Exploratory Research Laboratories I, Daiichi Pharmaceutical Co. Ltd.,

• 曽我 恒彦

  Exploratory Research Laboratories I, Daiichi Pharmaceutical Co. Ltd.,

• 魚戸 浩一

  Exploratory Research Laboratories I, Daiichi Pharmaceutical Co. Ltd.,

• 塩谷 恵美子

  Exploratory Research Laboratories I, Daiichi Pharmaceutical Co., Ltd.,

• 長田 泰明

  Exploratory Research Laboratories I, Daiichi Pharmaceutical Co., Ltd.,

• 中山 清

  Exploratory Research Laboratories I Daiichi Pharmaceutical Co. Ltd.

• 魚戸 浩一

  Exploratory Research Laboratories I Daiichi Pharmaceutical Co. Ltd.

• 曽我 恒彦

  Exploratory Research Laboratories I Daiichi Pharmaceutical Co. Ltd.

• 塩谷 恵美子

  Exploratory Research Laboratories I Daiichi Pharmaceutical Co. Ltd.

• 長田 恭明

  Exploratory Research Laboratories I Daiichi Pharmaceutical Co. Ltd.

関連論文

• Regio- and Stereoselective Synthesis of Carbocyclic 2', 3'-Dideoxy-3'-fluoro Nucleosides as Potential Antiviral Agents
• Zinc Triflate-Promoted Glycosidation : Synthesis of Lipid A Disaccharide Intermediates
• A Useful Method for Deprotection of the Protective Allyl Group at the Anomeric Oxygen of Carbohydrate Moieties Using Tetrakis(triphenylphosphine)palladium
• Direct Transformation of O-Glycosides into Other O-Glycosides Using Trimethylsilyl Bromide and Zinc Bromide
• Synthesis and Biological Activities of Lipid A Analogs : Modification of a Glycosidically Bound Group with Chemically Stable Polar Acidic Groups and Lipophilic Groups on the Disaccharide Backbone with Tetradecanoyl or N-Dodecanoylglycyl Groups
• Direct Transformation of O-Glycoside into Glyosyl Bromide with the Combination of Trimethylsilyl Bromide and Zinc Bromide
• Synthesis and Biological Activities of Analogs of a Lipid A Biosynthetic Precursor : 1-O-Phosphono-oxyethyl-4'-O-phosphono-disaccharides with (R)-3-Hydroxytetradecanoyl or Tetradecanoyl Groups at Positions 2,3,2' and 3'
• A Novel Glycoside Anomerization Catalyzed by Trimethylsilyl Bromide and Zinc Bromide in Combination
• Synthesis and Antitumor Activity of Lipid A Analogs Having a Phosphonooxyehyl Group with α- or β-Configuration at Position 1
• Novel Stereoselective Glycosidation by the Combined Use of Trityl Halide and Lewis Acid
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• Syntheses of 1-(5'-Amino-5'-deoxy-β-D-xylofuranosyl) uracil and Its N_3-Methyl Derivative
• Synthesis and Antiallergy Activity of [1,3,4]Thiadiazolo[3,2-α]-1,2,3-triazolo[4,5-d]pyrimidin-9(3H)-one Derivatives. II. 6-Alkyl- and 6-Cycloalkylalkyl Derivatives
• Facile Total Synthesis of Carbonolides by Witting-Hoener Macro-Cyclization and Stereoselective Epoxidation

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