(3R,4R,5R,6S)-hexahydro-3,4,5,6-tetrahydroxy-1H-azepine | 130790-29-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂环庚烷
• 英文名称: (3R,4R,5R,6S)-hexahydro-3,4,5,6-tetrahydroxy-1H-azepine
• 英文别名: 1,6-dideoxy-1,6-imino-(2S,3R,4R,5R)-D-glucitol；(3R,4R,5R,6S)-3,4,5,6-tetrahydroxyazepane；(3R,4R,5R,6S)-3,4,5,6-tetrahydroxyazepine；3(R),4(R),5(R),6(S)-tetrahydroxyazepane；(2S,3R,4R,5R)-tetrahydroxyazepane；1,6-Imino-1,6-didesoxy-D-glucit；(3S,4R,5R,6R)-azepane-3,4,5,6-tetrol
• CAS: 130790-29-3
• 化学式: C₆H₁₃NO₄
• 分子量: 163.174
• InChiKey: MRFFNLOQLBWKPJ-JGWLITMVSA-N

物化性质

• 沸点：
  328.6±42.0 °C(Predicted)
• 密度：
  1.508±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.9
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  93
• 氢给体数：
  5
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3R,4R,5R,6S)-hexahydro-3,4,5,6-tetrahydroxy-1H-azepine 在 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 12.0h， 以98%的产率得到1,6-dideoxy-1,6-imino-(2S,3R,4R,5R)-D-glucitol hydrochloride
  参考文献：
  名称：

  Concise and practical route to tri- and tetra-hydroxy seven-membered iminocyclitols as glycosidase inhibitors from d-(+)-glucurono-γ-lactone

  摘要：

  An efficient and short total synthesis of tetrahydroxy-1c and trihydroxy-azepane id is reported in 72% and 57% overall yields, respectively, from D-(+)-glucurono-gamma-lactone. Thus, D-glucuronolactone 2 on acetonide protection. DIBAL-H reduction and one-pot intermolecular reductive amination followed by -NCbz protection afforded 6-(N-benzyl-N-benzyloxycarbonyl) amino-6-deoxy-1,2-O-isopropylidene-alpha-D-gluco-1,4-furanose 5a. 1,2-Acetonide hydrolysis in 5a and Pd-mediated intramolecular reductive aminocyclization afforded tetrahydroxyazepane 1c. An analogous pathway with 5-deoxy-1,2-O-isopropylidene-alpha-D-glucurono-6,3-lactone 3b gave trihydroxy-azepane id. Glycosidase inhibitory activity of 1c/1d was studied and id was found to be potent inhibitor of alpha-mannosidase and beta-galactosidase. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2010.08.060
• 作为产物：
  描述：

  6-amino-6-deoxy-1,2-O-isopropylidene-α-D-glucofuranose 在 palladium on activated charcoal 氢气 、 碳酸氢钠 、 三氟乙酸 作用下， 以 甲醇 、 水 为溶剂， 25.0 ℃ 、551.58 kPa 条件下， 反应 22.0h， 生成 (3R,4R,5R,6S)-hexahydro-3,4,5,6-tetrahydroxy-1H-azepine
  参考文献：
  名称：

  Concise and practical synthesis of (2S,3R,4R,5R) and (2S,3R,4R,5S)-1,6-dideoxy-1,6-iminosugars

  摘要：

  The syntheses of (2S,3R,4R,5R) and (2S,3R,4R,5S)-1,6-dideoxy-1,6 iminosugars 1a and 1b, respectively, from D-glucose are described. The key transformations in this reaction sequence include regio-selective epoxide ring opening with N-benzylamine followed by intramolecular reductive amination of amino-aldehyde. (C) 2003 Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4020(03)00177-7

文献信息

• Enzymatic/Chemical Synthesis and Biological Evaluation of Seven-Membered Iminocyclitols
  作者：Francisco Morís-Varas、Xin-Hua Qian、Chi-Huey Wong

  DOI：10.1021/ja960975c

  日期：1996.1.1

  a C2 symmetry axis, and N-acetylglucosamine to a 6-acetamidoiminocyclitol. Asymmetrization of the meso azasugar was carried out by chemical means, to yield a 3-methoxy-4,5,6-trihydroxyazepane. An attempted enzymatic synthesis of the methoxy derivatives of these azasugars was unsuccessful, leading, however, to both enantiomers of 1-deoxy-2-O-methylmannojirimycin. Some of these c...

  已经通过化学酶促或化学合成获得了几种多羟基全氢氮杂。(±)-3-叠氮基-2-羟基丙醛和磷酸二羟丙酮 (DHAP) 在 DHAP 依赖性醛缩酶存在下缩合，然后用酸性磷酸酶和异构酶处理得到 6-叠氮基-6-脱氧吡喃糖，其在还原胺化后得到标题化合物。亚氨基环醇也可以通过吡喃醛糖的化学操作获得，保护为苄基糖苷或二异丙叉基醚。因此，d-半乳糖产生内消旋 3,4,5,6-四羟基全氢氮杂，d-甘露糖产生具有 C2 对称轴的衍生物，N-乙酰氨基葡萄糖产生 6-乙酰氨基亚氨基环醇。通过化学方法进行内消旋氮杂糖的不对称化，得到 3-甲氧基-4,5,6-三羟基氮杂环庚烷。对这些氮杂糖的甲氧基衍生物的酶促合成尝试未成功，但导致了 1-脱氧-2-O-甲基甘露尻霉素的两种对映异构体。其中一些...
• Synthesis of New N-Containing Maltooligosaccharides, .ALPHA.-Amylase Inhibitors, and Their Biological Activities.
  作者：Riichiro UCHIDA、Ayako NASU、Shoichi TOKUTAKE、Kouichi KASAI、Koichiro TOBE、Nobuyuki YAMAJI

  DOI：10.1248/cpb.47.187

  日期：——

  Fifteen new N-containing maltooligosaccharides were obtained using the chemoenzymatic method. Among these compounds, maltooligosaccharides having 6-amino-6-deoxy-D-sorbitol residue, (3R, 4R, 5R, 6S)-hexahydro-3, 4, 5, 6-tetrahydroxy-1H-azepine residue, and (3R, 5R)-3, 4, 5-trihydroxypiperidine residue at the reducing end showed strong inhibitory activities for human pancreatic α-amylase (HPA) (EC 3.2.1.1) and human salivary α-amylase (HSA). The administration of (3R, 4R, 5R, 6S)-hexahydro-3, 5, 6-trihydroxy-1H-azepine-4-yl O-α-D-glucopyranosyl-(1→4)-α-D-glucopyranoside (13, IC50=4.3×10-5M for HPA, IC50=8.2×10-5M for HSA) and (3R, 5R)-3, 5-dihydroxypiperidine-4-yl O-α-D-glucopyranosyl-(1→4)-α-D-glucopyranoside (18, IC50=3.4×10-5M for HPA, IC50=4.6×10-5M for HSA) to ICR mice suppressed postprandial hyperglycemia.

  利用化学酶法获得了 15 种新的含 N 的麦芽寡糖。在这些化合物中，还原端具有 6-氨基-6-脱氧-D-山梨醇残基、(3R, 4R, 5R, 6S)-hexahydro-3, 4, 5, 6-tetrahydroxy-1H-azepine 残基和 (3R, 5R)-3, 4, 5-trihydroxypiperidine 残基的麦芽寡糖对人胰腺α-淀粉酶（HPA）（EC 3.2.1.1）和人唾液α-淀粉酶（HSA）有很强的抑制活性。服用(3R, 4R, 5R, 6S)-六氢-3, 5, 6-三羟基-1H-氮杂卓-4-基 O-α-D-吡喃葡萄糖苷-(1→4)-α-D-吡喃葡萄糖苷（13，对 HPA 的 IC50=4.3×10-5M, 对 HSA 的 IC50=8.2×10-5M for HSA）和 (3R，5R)-3，5-二羟基哌啶-4-基 O-α-D-吡喃葡萄糖基-(1→4)-α-D-吡喃葡萄糖苷（18，IC50=3.4×10-5M for HPA，IC50=4.6×10-5M for HSA）给 ICR 小鼠服用可抑制餐后高血糖。
• Lohray; Bhushan, Vidya; Prasuna, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1999, vol. 38, # 12, p. 1311 - 1321
  作者：Lohray、Bhushan, Vidya、Prasuna、Jayamma、Raheem、Papireddy、Umadevi、Premkumar、Lakshmi、Narayanareddy

  DOI：——

  日期：——
• Concise and practical synthesis of (2S,3R,4R,5R) and (2S,3R,4R,5S)-1,6-dideoxy-1,6-iminosugars
  作者：Jayant N Tilekar、Nitin T Patil、Harishchandra S Jadhav、Dilip D Dhavale

  DOI：10.1016/s0040-4020(03)00177-7

  日期：2003.3

  The syntheses of (2S,3R,4R,5R) and (2S,3R,4R,5S)-1,6-dideoxy-1,6 iminosugars 1a and 1b, respectively, from D-glucose are described. The key transformations in this reaction sequence include regio-selective epoxide ring opening with N-benzylamine followed by intramolecular reductive amination of amino-aldehyde. (C) 2003 Published by Elsevier Science Ltd.
• An easy route to seven-membered iminocyclitols from aldohexopyranosyl enamines
  作者：José Fuentes、Consolación Gasch、David Olano、M.Ángeles Pradera、Guillermo Repetto、Francisco J. Sayago

  DOI：10.1016/s0957-4166(02)00377-4

  日期：2002.8

  A new stereocontrolled and high yielding synthesis of biologically active polyhydroxyperhydroazelpines is reported starting from easily available glycosylenamines (D-gluco, D-manno, and D-galacto configurations), which are transformed into 1,6-azaanhydropyranose derivatives. O- and N-Deprotection of the latter, followed by reduction with sodium cyanoborohydride, gives the target chiral iminocyclitols. The method is based on the capacity of the dialkoxycarbonylvinyl group to stabilize an amide ion, and the only limitation is the necessity for the starting glycosylenamine to have beta-D-configuration. The inhibitory activity of several intermediate iminocyclitols and aldopyranosylenamines on different alpha- and beta-glycosidases is also reported. (C) 2002 Published by Elsevier Science Ltd.