(1R,2R,3R,7R,7AR)-六氢-3-(羟基甲基)-1H-吡咯里嗪-1,2,7-三醇 | 126655-21-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯里西啶类
• 中文名称: (1R,2R,3R,7R,7AR)-六氢-3-(羟基甲基)-1H-吡咯里嗪-1,2,7-三醇
• 英文名称: 7-epi-australine
• 英文别名: (-)-(1R,2R,3R,7R,7aR)-hexahydro-3-hydroxymethyl-1H-pyrrolizine-1,2,7-triol；7,7a-diepialexine；3-(Hydroxymethyl)-1,2,7-trihydroxypyrrolizidine；(1R,2R,3R,7R,8R)-3-(hydroxymethyl)-2,3,5,6,7,8-hexahydro-1H-pyrrolizine-1,2,7-triol
• CAS: 126655-21-8
• 化学式: C₈H₁₅NO₄
• 分子量: 189.211
• InChiKey: AIQMLBKBQCVDEY-FMDGEEDCSA-N

物化性质

• 沸点：
  417.4±28.0 °C(Predicted)
• 密度：
  1.53±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.7
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  84.2
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (1R,2R,3R,7R,7AR)-六氢-3-(羟基甲基)-1H-吡咯里嗪-1,2,7-三醇 、 乙酸酐 在 吡啶 作用下， 反应 24.0h， 以97%的产率得到(1R,2R,3R,7R,7aR)-1,2,7-triacetoxy-3-(acetoxymethyl)hexahydro-1H-pyrrolizine
  参考文献：
  名称：

  Synthesis of (−)-7-Epiaustraline and (−)-1-Epicastanospermine

  摘要：

  Highly efficient and selective syntheses of the title compounds are described. The cornerstone of the synthetic plan is the tandem inter [4 + 2]/inter [3 + 2] cycloaddition process. These syntheses differ from previous applications of this strategy in that they incorporate an alkylation in the hydrogenolysis step to close the second ring of the azabicyclic systems. Notable features of the sequence are (1) the highly regio- and stereoselective [3 + 2] cycloaddition of nitronate 15 with siloxymethyl (Z)-beta-silylvinyl ketone (Z)-22b and (2) the highly selective reduction of the resulting ketone 24a with L-Selectride. A single-crystal X-ray structure analysis of synthetic (-)-7-epiaustraline confirmed that the targeted structure was successfully synthesized. This stimulated a reexamination of the structural assignment of the natural product. (-)-1-Epicastanospermine was synthesized in four steps from the common intermediate 27a. The absolute configuration of (-)-1-epicastanospermine was assured by single-crystal X-ray structure analysis of intermediate (-)-27a. Thus, the sign of the optical rotation had to be revised. The overall efficiency of these syntheses were 9 steps and 23% yield for (-)-7-epiaustraline and 10 steps and 20% yield for (-)-1-epicastanospermine.

  DOI：

  10.1021/jo991990d
• 作为产物：
  描述：

  (E)-5-(4-methoxybenzyloxy)pent-2-en-1-ol 在 titanium(IV) isopropylate 、 silica gel 、 palladium dichloride 吡啶 、 叔丁基过氧化氢 、 ruthenium trichloride 、 sodium hydroxide 、 potassium osmate(VI) 、 sodium periodate 、 氯化亚砜 、 calcium hydride 、 草酰氯 、 偶氮二甲酸二异丙酯 、 水 、 氢气 、 双(三甲基硅烷基)氨基钾 、 potassium carbonate 、 lithium trifluoromethanesulfonate 、 D-(-)-酒石酸二异丙酯 、 caesium carbonate 、 二甲基亚砜 、 N-甲基吗啉氧化物 、 三乙胺 、 三苯基膦 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 四氢呋喃 、 甲醇 、 四氯化碳 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 甲苯 、 乙腈 为溶剂， 反应 248.75h， 生成 (1R,2R,3R,7R,7AR)-六氢-3-(羟基甲基)-1H-吡咯里嗪-1,2,7-三醇
  参考文献：
  名称：

  Asymmetric Synthesis of (−)-7-Epiaustraline and (+)-1,7-Diepiaustraline

  摘要：

  A diastereoselective and modular approach to the synthesis of the 3-hydroxymethyl-2,3,5,6,7,7a-hexahydro-1H-pyrrolizine-1,2,7-triol structure, characteristic of several natural pyrrolizidine natural products, has been developed. This approach culminated in the synthesis of (-)-7-epiaustraline and (+)-1,7-diepiaustraline. The oxazolidinone group has been found to be a useful protecting group in the RCM reaction and, as part of a pyrrolo[1,2-c]oxazol-3-one ring system, has functioned as a stereo- and regio-directing group in a key diastereoselective cis-dihydroxylation reaction and a regioselective nucleophilic ring-opening of a S,S-dioxo-dioxathiole.

  DOI：

  10.1021/jo034914q

文献信息

• Stereocomplementary Routes to Hydroxylated Nitrogen Heterocycles: Total Syntheses of Casuarine, Australine, and 7-<i>epi</i>-Australine
  作者：Camilla Parmeggiani、Francesca Cardona、Leonardo Giusti、Hans-Ulrich Reissig、Andrea Goti

  DOI：10.1002/chem.201301320

  日期：2013.8.5

  occurred with perfect diastereoselectivity furnishing a bicyclic 1,2‐oxazine derivative, which is an excellent precursor for pyrrolizidine alkaloids hydroxylated at C‐7 with optional configuration at this stereogenic center. Depending on the stage of the NO bond cleavage and ring re‐closure, 7‐hydroxypyrrolizidines with 7R or 7S configuration were obtained, as a result of completely selective addition reactions

  向D-阿拉伯糖衍生的环状硝酮中添加锂化的1-苄氧基丙二烯具有完美的非对映选择性，从而提供了双环1,2-恶嗪衍生物，这是在C-7处羟基化的吡咯并烷生物碱的极佳前体，在该立体异构中心具有可选构型。根据内环C底部或顶部互补发生的完全选择加成反应的结果，根据NO键断裂和环重新闭合的阶段，获得了具有7 R或7 S构型的7-羟基吡咯烷核苷六元和五元B环中的C双键。这些有效的立体异构途径可用于获得多羟基吡咯烷核生物碱，这是通过木麻黄碱和奥沙林的有效合成证明的，这是两类不同构型的7-羟基吡咯烷核生物碱的实例。australine的替代性合成和7-制备两种策略外延-australine也报道，这表明，氢化物还原环外的C的立体选择性 Ô双键独立于环的大小，从顶面优先发生六元或五元环。
• Synthesis and Glycosidase Inhibition of Australine and Its Fluorinated Derivatives
  作者：Yi-Xian Li、Yousuke Shimada、Kasumi Sato、Atsushi Kato、Wei Zhang、Yue-Mei Jia、George W. J. Fleet、Min Xiao、Chu-Yi Yu

  DOI：10.1021/ol503728e

  日期：2015.2.6

  d-arabinose-derived cyclic nitrone 11. Fluorination at the C-7 position enhanced the inhibition against A. niger α-glucosidase, and this constitutes the first example of fluorination substitution for a hydroxyl increasing the inhibition of any glycosidases. The enantiomers synthesized from nitrone ent-11 showed no inhibition of the corresponding enzymes.

  Australine（1），7- epi- australine（2）及其C-7氟化衍生物4和5是从d-阿拉伯糖衍生的环硝酮11有效合成的。C-7位的氟化作用增强了对黑曲霉α-葡萄糖苷酶的抑制作用，这构成了氟化取代羟基以增加对任何糖苷酶的抑制作用的第一个例子。从硝酮合成对映异构体ENT -11没有表现出抑制相应的酶。
• Synthesis of (1<i>R</i>,2<i>R</i>,3<i>R</i>,7<i>R</i>,7a<i>R</i>)-Hexahydro-3-(Hydroxymethyl)-1<i>H</i>-pyrrolizine-1,2,7-triol:  7-Epiaustraline
  作者：Scott E. Denmark、B. Herbert

  DOI：10.1021/ja980705p

  日期：1998.7.1
• A synthesis of (+)-7-Epiaustraline and (−)-7-Epialexine
  作者：William H. Pearson、Jennifer V. Hines

  DOI：10.1016/0040-4039(91)80071-d

  日期：1991.9

  Reductive cyclization of the azido epoxides 19-alpha and 19-beta followed by deprotection afforded the HIV inhibitor (+)-7-epiaustraline 7 and (-)-7-epialexine 9. The formation of 7 proceeded with an unusual inversion of configuration at C-7.
• TREATMENT OF LYSOSOMAL STORAGE DISORDERS AND OTHER PROTEOSTATIC DISEASES
  申请人：De Moor Olivier

  公开号：US20110237538A1

  公开（公告）日：2011-09-29

  Described are various compounds, in particular iminosugars, and methods for the treatment of proteostatic diseases, in particular lysosomal storage disorders. The compound may be a pharmacoperone of an enzyme selected from: (a) Acid alpha-glucosidase; (b) Acid beta-glucosidase; (c) glucocerebrosidase; (d) alpha-Galactosidase A; (e) Acid beta-galactosidase; (f) beta-Hexosaminidase A; (g) beta-Hexosaminidase B; (h) Acid sphingomyelinase; (i) Galactocerebrosidase; (j) Acid ceramidase; (k) Arylsulfatase A; (l) alpha-L-Iduronidase; (m) Iduronate-2-sulfatase; (n) Heparan N-sulfatase; (o) alpha-N-Acetylglucosaminidase; (p) Acetyl-CoA: alpha-glucosaminide N-acetyltransferase; (q) N-Acetylglucosamine-6-sulfate sulfatase; (r) N-Acetylgalactosamine-6-sulfate sulfatase; (s) Acid beta-galactosidase; (t) Arylsulfatase B; (u) beta-Glucuronidase; (v) Acid alpha-mannosidase; (w) Acid beta-mannosidase; (x) Acid alpha-L-fucosidase; (y) Sialidase; and (z) alpha-N-acetylgalactosaminidase.