1,4-dideoxy-1,4-(butyliminiumyl)-D-arabinitol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 1,4-dideoxy-1,4-(butyliminiumyl)-D-arabinitol
• 英文别名: 1,4-dideoxy-1,4-(butylimino)-D-arabinitol；(2R,3R,4R)-1-butyl-3,4-dihydroxy-2-hydroxymethylpyrrolidine；(2R,3R,4R)-1-butyl-2-(hydroxymethyl)pyrrolidine-3,4-diol
• 化学式: C₉H₁₉NO₃
• 分子量: 189.255
• InChiKey: AORXTDSJOOFVRB-IWSPIJDZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  63.9
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  methyl-1,3-di-O-isopropylidene-α-D-fructofuranoside 在 咪唑 、 三乙基硅烷 、 硼烷四氢呋喃络合物 、 C₄H₁₀BF₃O*(x)H₂O 、 palladium 10% on activated carbon 、 氢气 、 碘 、 sodium hydride 、 对甲苯磺酸 、 臭氧 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， -78.0~20.0 ℃ 、405.33 kPa 条件下， 反应 75.58h， 生成 1,4-dideoxy-1,4-(butyliminiumyl)-D-arabinitol
  参考文献：
  名称：

  A Versatile Approach to N-Alkylated 1,4-Dideoxy-1,4-imino-d-arabinitols and 1,4-Dideoxy-1,4-imino-l-xylitols

  摘要：

  A versatile and concise synthesis of N-alkylated 1,4-dideoxy-1,4-imino-D-arabinitol and 1,4-dideoxy-1,4-imino-L-xylitol derivatives is described. These were prepared using pseudohemiketal lactams as key intermediates, which in turn were obtained from sucrose. The key intermediates were prepared by a diastereospecific tandem reaction which facilitated the introduction of various substituents on the nitrogen atom of the iminosugars.

  DOI：

  10.1021/jo1020322

文献信息

• Use of glycogen phosphorylase inhibitors for treatment of cardiovascular diseases
  申请人：——

  公开号：US20040082641A1

  公开（公告）日：2004-04-29

  The present invention provides methods of treatment and prevention of early cardiac and early cardiovascular diseases, for instance of ischemic origin, such as left ventricular hypertrophy, coronary artery disease, essential hypertension, acute hypertensive emergency, cardiomyopathy, heart insufficiency, exercise tolerance, chronic heart failure, arrhythmia, cardiac dysrhythmia, syncopy, arteriosclerosis, mild chronic heart failure, angina pectoris, cardiac bypass reocclusion, intermittent claudication (arteriosclerosis oblitterens), diastolic dysfunction and systolic dysfunction, as well as improving the success of heart transplantations, through administration of glycogen phosphorylase inhibitor compounds.

  本发明提供了治疗和预防早期心脏和早期心血管疾病的方法，例如缺血性疾病，如左心室肥大，冠状动脉疾病，高血压，急性高血压紧急情况，心肌病，心力衰竭，运动耐受性，慢性心力衰竭，心律失常，心脏心律失常，晕厥，动脉硬化，轻度慢性心力衰竭，心绞痛，心脏旁路再闭塞，间歇性跛行（闭塞性动脉硬化），舒张功能和收缩功能障碍，以及通过给予糖原磷酸化酶抑制剂化合物来提高心脏移植的成功率。
• Use of 3,4-dihydroxy-2-hydroxymethylpyrrolidine for the treatment of diabetes
  申请人：NOVO NORDISK A/S

  公开号：EP0884050A1

  公开（公告）日：1998-12-16

  (2R,3R,4R)-3,4-dihydroxy-2-hydroxymethylpyrrolidine and other substituted 2-methylpyrrolidines can be used for the treatment of diabetes.

  (2R,3R,4R)-3,4-二羟基-2-羟甲基吡咯烷和其他取代的 2-甲基吡咯烷可用于治疗糖尿病。
• Use of 2-alkylpyrrolidines for the treatment of diabetes
  申请人：NOVO NORDISK A/S

  公开号：EP1040827A2

  公开（公告）日：2000-10-04

  (2R,3R,4R)-3,4-dihydroxy-2-hydroxymethylpyrrolidine and other substituted 2-methylpyrrolidines can be used for the treatment of diabetes.

  (2R,3R,4R)-3,4-二羟基-2-羟甲基吡咯烷和其他取代的 2-甲基吡咯烷可用于治疗糖尿病。
• [EN] 2-ALKYLPYRROLIDINES<br/>[FR] 2-ALKYLPYRROLIDINES
  申请人：NOVO NORDISK A/S

  公开号：WO1997009040A1

  公开（公告）日：1997-03-13

  (EN) (2R, 3R, 4R)-3,4-dihydroxy-2-hydroxymethylpyrrolidine and other substituted 2-methylpyrrolidines can be used for the treatment of diabetes.(FR) Il est possible, pour le traitement du diabète, d'utiliser la (2R, 3R, 4R)-3, 4-dihydroxy-2-hydroxyméthylpyrrolidine et d'autres 2-méthylpyrrolidines à substitution.

  （2R,3R,4R）-3、4-二羟基-2-羟甲基pyrrolidine及其取代的2-甲基pyrrolidine可用于治疗糖尿病。 （法语翻译的中文版本可参考：） 可以用于治疗糖尿病的（2R,3R,4R）-3、4-二羟基-2-羟甲基旋盘腺苷及其取代的2-甲基旋盘腺苷。
• N-Alkylated Nitrogen-in-the-Ring Sugars: Conformational Basis of Inhibition of Glycosidases and HIV-1 Replication
  作者：Naoki Asano、Haruhisa Kizu、Kengo Oseki、Emiko Tomioka、Katsuhiko Matsui、Mika Okamoto、Masanori Baba

  DOI：10.1021/jm00013a012

  日期：1995.6

  The conformations of nitrogen-in-the-ring sugars and their N-alkyl derivatives were studied from H-1 NMR analyses, mainly using (3)J(H,H) coupling constants and quantitative NOE experiments. No significant difference was seen in the ring conformation of 1-deoxynojirimycin (1), N-methyl-1-doexynojirimycin (2), and N-butyl-1-deoxynojirimycin (3). However, it was shown that the C6 OH group in 1 is predominantly equatorial to the piperidine ring, while that in 2 or 3 is predominantly axial, and its N-alkyl group is oriented equatorially. In the furanose analogues 1,4-dideoxy-1,4-imino-D-arabinitol (4) and its N-methyl (5) and N-butyl (6) derivatives, the five-membered ring conformation differed significantly by the presence or absence of the N-substituted group and the length of the N-alkyl chain. Compound 3 reduced its inhibitory effect on almost all glycosidases, resulting in an extremely specific inhibitor for processing alpha-glucosidase I since N-alkylation of 1 is known to enhance both the potency and specificity of this enzyme in vitro and in vivo. This preferred (C6 OH axial) conformation in 2 and 3 appears to be responsible for their strong alpha-glucosidase I activity. Compound 4 is a good inhibitor of intestinal alpha-glucohydrolases, alpha-glucosidase II, and Golgi alpha-mannosidases I and II, but its N-alkyl derivatives 5 and 6 markedly decreased inhibitory potential for all enzymes tested. In the case of 2,5-dideoxy-2,5-imino-D-mannitol (DMDP, 7), which is a potent beta-galactosidase inhibitor, its N-methyl (8) and N-butyl (9) derivatives completely lost potency toward beta-galactosidase as well. N-Alkylation of compounds 4 and 7, known well as potent yeast alpha-glucosidase inhibitors, resulted in a serious lass of inhibitory activity toward yeast alpha-glucohydrolases. Activity of these nine sugar analogues against HIV-1 replication was determined, based on the inhibition of virus-induced cytopathogenicity in MT-4 and MOLT-4 cells. Compounds 2 and 3, which are better inhibitors of alpha-glucosidase I than 1, proved active with EC(50) values of 69 and 49 mu g/mL in MT-4 cells and 100 and 37 mu g/mL in MOLT-4 cells, respectively, while none of the furanose analogues exhibited any inhibitory effects on HIV-1. The change in potency and specificity of bioactivity by N-alkylation of nitrogen-in-the-ring sugars appears to be correlated with their conformational change.