3-C-azidomethyl-2,3-O-isopropylidene-D-erythrose | 1314878-16-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-C-azidomethyl-2,3-O-isopropylidene-D-erythrose
• 英文别名: isopropylidene 3-C-azidomethyl-D-erythrose；(3aR,6aR)-3a-(azidomethyl)-2,2-dimethyl-6,6a-dihydro-4H-furo[3,4-d][1,3]dioxol-6-ol
• CAS: 1314878-16-4
• 化学式: C₈H₁₃N₃O₄
• 分子量: 215.209
• InChiKey: RWRYUQOMVNQCTR-OHEWIBQUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  62.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-C-azidomethyl-2,3-O-isopropylidene-D-erythrose 在 palladium 10% on activated carbon 、 氢气 作用下， 以 1,4-二氧六环 、 水 、 溶剂黄146 为溶剂， 反应 60.0h， 生成 1,4-dideoxy-2-C-hydroxymethyl-1,4-imino-L-threitol
  参考文献：
  名称：

  C-Branched Iminosugars: α-Glucosidase Inhibition by Enantiomers of isoDMDP, isoDGDP, and isoDAB–l-isoDMDP Compared to Miglitol and Miglustat

  摘要：

  The Ho crossed aldol condensation provides access to a series of carbon branched iminosugars as exemplified by the synthesis of enantiomeric pairs of isoDMDP, isoDGDP, and isoDAB, allowing comparison of their biological activities with three linear isomeric natural products DMDP, DGDP, and DAB and their enantiomers. L-IsoDMDP [(2S,3S,4R)-2,4-bis(hydroxymethyl)pyrrolidine-3,4-diol], prepared in 11 steps in an overall yield of 4596 from D-lyxonolactone, is a potent specific competitive inhibitor of gut disaccharidases [K-i 0.081 mu M for rat intestinal maltase] and is more effective in the suppression of hyperglycaemia in a maltose loading test than miglitol, a drug presently used in the treatment of late onset diabetes. The partial rescue of the defective F508del-CFTR function in CF-KM4 cells by L-isoDMDP is compared with miglustat and isoLAB in an approach to the treatment of cystic fibrosis.

  DOI：

  10.1021/jo4005487
• 作为产物：
  描述：

  2-C-hydroxymethyl-2,3:5,6-di-O-isopropylidene-D-mannono-1,4-lactone 在 吡啶 、 sodium tetrahydroborate 、 sodium periodate 、 sodium azide 、 二异丁基氢化铝 、 溶剂黄146 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 44.0h， 生成 3-C-azidomethyl-2,3-O-isopropylidene-D-erythrose
  参考文献：
  名称：

  C-Branched Iminosugars: α-Glucosidase Inhibition by Enantiomers of isoDMDP, isoDGDP, and isoDAB–l-isoDMDP Compared to Miglitol and Miglustat

  摘要：

  The Ho crossed aldol condensation provides access to a series of carbon branched iminosugars as exemplified by the synthesis of enantiomeric pairs of isoDMDP, isoDGDP, and isoDAB, allowing comparison of their biological activities with three linear isomeric natural products DMDP, DGDP, and DAB and their enantiomers. L-IsoDMDP [(2S,3S,4R)-2,4-bis(hydroxymethyl)pyrrolidine-3,4-diol], prepared in 11 steps in an overall yield of 4596 from D-lyxonolactone, is a potent specific competitive inhibitor of gut disaccharidases [K-i 0.081 mu M for rat intestinal maltase] and is more effective in the suppression of hyperglycaemia in a maltose loading test than miglitol, a drug presently used in the treatment of late onset diabetes. The partial rescue of the defective F508del-CFTR function in CF-KM4 cells by L-isoDMDP is compared with miglustat and isoLAB in an approach to the treatment of cystic fibrosis.

  DOI：

  10.1021/jo4005487

文献信息

• [EN] PYRROLIDINE IMINOSUGARS USED IN THE TREATMENT OF CYSTIC FIBROSIS<br/>[FR] IMINOSUCRES DE PYRROLIDINE UTILISÉS DANS LE TRAITEMENT DE LA MUCOVISCIDOSE
  申请人：SUMMIT CORP PLC

  公开号：WO2011086347A1

  公开（公告）日：2011-07-21

  A compound of formula (I) wherein: R1 is selected from H; linear or branched, substituted or unsubstituted alkyl, alkenyl, alkynyl and aralkyl and wherein the optional substitution may be with one or more groups independently selected from: -OH; -F; -Cl; -Br; -I; -NH2; alkylamino; dialkylamino; linear or branched alkyl, alkenyl, alkynyl and aralkyl; aryl; heteroaryl; linear or branched alkoxy; aryloxy; aralkoxy; -(alkylene)oxy(alkyl); -CN; -NO2; - COOH; -COO(alkyl); -COO(aryl); -C(O)NH(alkyl); -C(O)NH(aryl); sulfonyl; alkylsulfonyl; arylsulfonyl; sulfamoyl; alkylsulfamoyl; alkylthio; alkylsulfonamide; arylsulfonamide; -NHNH2; and -NHOH; or a bioisostere, pharmaceutically acceptable salt or derivative thereof, finds application in the treatment of cystic fibrosis.

  化合物的化学式（I），其中：R1选自H；线性或支链、取代或未取代的烷基、烯基、炔基和芳基，其中可选的取代基可与一个或多个独立选择的基团取代，包括：-OH；-F；-Cl；-Br；-I；-NH2；烷基氨基；二烷基氨基；线性或支链烷基、烯基、炔基和芳基；芳基；杂环芳基；线性或支链烷氧基；芳氧基；芳基烷氧基；-(烷基)氧(烷基)；-CN；-NO2；-COOH；-COO(烷基)；-COO(芳基)；-C(O)NH(烷基)；-C(O)NH(芳基)；磺酰基；烷基磺酰基；芳基磺酰基；磺胺基；烷基磺胺基；烷基硫基；烷基磺酰胺；芳基磺酰胺；-NHNH2；和-NHOH；或其生物同位素，药用盐或衍生物，在囊性纤维化的治疗中有应用。
• Cystic fibrosis and diabetes: isoLAB and isoDAB, enantiomeric carbon-branched pyrrolidine iminosugars
  作者：Daniel Best、Sarah F. Jenkinson、A. Waldo Saville、Dominic S. Alonzi、Mark R. Wormald、Terry D. Butters、Caroline Norez、Frederic Becq、Yves Blériot、Isao Adachi、Atsushi Kato、George W.J. Fleet

  DOI：10.1016/j.tetlet.2010.05.131

  日期：2010.8

  Acetonides are the only protecting groups used in the syntheses of isoDAB from D-ribose and of isoLAB from D-tagatose. isoDAB is a potent and highly specific competitive a-glucosidase inhibitor (for rice alpha-glucosidase, K(i) = 4 mu M for isoDAB compared to K(i) 14 mu M for DAB). isoDAB is not an whereas DAB is a potent inhibitor of glycogen phosphorylase. This is the first example of any potent inhibition of glycosidases by a carbon-branched iminosugar pyrrolidine. Although isoLAB shows no inhibition of any glycosidase, preliminary experiments suggest that isoLAB partially rescues the defective F508del-CFTR function and so may have a role in the study of cystic fibrosis. (C) 2010 Elsevier Ltd. All rights reserved.
• <i>C</i>-Branched Iminosugars: α-Glucosidase Inhibition by Enantiomers of isoDMDP, isoDGDP, and isoDAB–<scp>l</scp>-isoDMDP Compared to Miglitol and Miglustat
  作者：Sarah F. Jenkinson、Daniel Best、A. Waldo Saville、James Mui、R. Fernando Martínez、Shinpei Nakagawa、Takahito Kunimatsu、Dominic S. Alonzi、Terry D. Butters、Caroline Norez、Frederic Becq、Yves Blériot、Francis X. Wilson、Alexander C. Weymouth-Wilson、Atsushi Kato、George W. J. Fleet

  DOI：10.1021/jo4005487

  日期：2013.8.2

  The Ho crossed aldol condensation provides access to a series of carbon branched iminosugars as exemplified by the synthesis of enantiomeric pairs of isoDMDP, isoDGDP, and isoDAB, allowing comparison of their biological activities with three linear isomeric natural products DMDP, DGDP, and DAB and their enantiomers. L-IsoDMDP [(2S,3S,4R)-2,4-bis(hydroxymethyl)pyrrolidine-3,4-diol], prepared in 11 steps in an overall yield of 4596 from D-lyxonolactone, is a potent specific competitive inhibitor of gut disaccharidases [K-i 0.081 mu M for rat intestinal maltase] and is more effective in the suppression of hyperglycaemia in a maltose loading test than miglitol, a drug presently used in the treatment of late onset diabetes. The partial rescue of the defective F508del-CFTR function in CF-KM4 cells by L-isoDMDP is compared with miglustat and isoLAB in an approach to the treatment of cystic fibrosis.