3-epi-casuarine | 729593-71-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯里西啶类
• 英文名称: 3-epi-casuarine
• 英文别名: MNLP-462A；(1R,2R,3S,6S,7S,8R)-3-(hydroxymethyl)-2,3,5,6,7,8-hexahydro-1H-pyrrolizine-1,2,6,7-tetrol
• CAS: 729593-71-9
• 化学式: C₈H₁₅NO₅
• 分子量: 205.211
• InChiKey: AXTGOJVKRHFYBT-JKVYXWIHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.7
• 重原子数：
  14
• 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：
  104
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-epi-casuarine 、 乙酸酐 在 吡啶 、 4-二甲氨基吡啶 作用下， 反应 12.0h， 以66%的产率得到(1R,2R,3S,6S,7S,7aR)-3-(acetoxymethyl)hexahydro-1H-pyrrolizine-1,2,6,7-tetrayl tetracetate
  参考文献：
  名称：

  Polyhydroxylated Pyrrolizidines. Part 7. Stereoselective Synthesis of Unnatural Analogs of (+)‐Casuarine from Partially Protected DGDP

  摘要：

  DOI：

  10.1080/07328300600735181
• 作为产物：
  描述：

  (R)-4-Azido-2,3-dihydroxy-4-((4S,5R,4'R)-2,2,2',2'-tetramethyl-[4,4']bi[[1,3]dioxolanyl]-5-yl)-butyric acid methyl ester 在 palladium hydroxide - carbon 吡啶 、 咪唑 、 甲醇 、 硼烷四氢呋喃络合物 、 水 、 氢气 、 sodium acetate 、 potassium carbonate 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 甲苯 、 丁酮 为溶剂， 反应 72.0h， 生成 3-epi-casuarine
  参考文献：
  名称：

  Isolation synthesis and glycosidase inhibition profile of 3-epi-casuarine

  摘要：

  3-epi-Casuarine, the first naturally occurring stereoisomer of casuarine, was isolated from Myrtus communis L. The glycosidase inhibition profile and NMR spectra of 3-epi-casuarine are compared with those of casuarine; the change in configuration at one of the six stereogenic centres causes a dramatic change in the conformation of the bicyclic system. The key step in the 6% overall yield synthesis of 3-epi-casuarine from D-gluconolactone is the efficient cyclization of a completely unprotected pentahydroxyaminomcsylate to the pyrrolizidine nucleus. A low yield synthesis of casuarine is also reported. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2006.10.005

文献信息

• [EN] SYNTHESIS OF POLYHYDROXYLATED ALKALOIDS<br/>[FR] SYNTHÈSE DES ALCALOÏDES POLYHYDROXYLÉS
  申请人：MNL PHARMA LTD

  公开号：WO2006008493A1

  公开（公告）日：2006-01-26

  A process for the production of a polyhydroxylated bicyclic (e.g. pyrrolizidine such as casuarine (10), indolizidine or quinolizidine) alkaloid comprises the cyclisation of a pyrrolidine or piperidine intermediate having three or more free hydroxyl groups.

  一种用于生产多羟基双环（例如吡咯里西啶，例如相思豆碱（10）、吲哚里西啶或喹诺里西啶）生物碱的过程，包括将具有三个或更多自由羟基的吡咯烷或哌啶中间体进行环合。
• ADJUVANT COMPOSITIONS
  申请人：Nash Robert James

  公开号：US20090047306A1

  公开（公告）日：2009-02-19

  An adjuvant composition comprises a Th1-activating alkaloid, optionally further comprising an auxiliary adjuvant selected from a type 2 adjuvant (e.g. alum and/or MF59), a type 1 adjuvant and/or a balanced adjuvant. Vaccines comprising the adjuvant composition include nucleic acid(s) which encode one or more antigenic protein(s); protein(s) or peptide(s); glycoprotein(s); polysaccharide(s) (e.g. carbohydrate(s)); fusion protein(s); lipid(s); glycolipid(s); peptide mimic(s) of polysaccharides carbohydrate(s) and a protein(s) in admixture; carbohydrate-protein conjugate(s); cells or extracts thereof; dead or attenuated cells or extracts thereof; tumour cells or extracts thereof; viral particles (e.g. attenuated viral particles or viral components); allergen(s) mixtures thereof.

  一种佐剂组合物包括一种Th1激活生物碱，可选地进一步包括一种辅助佐剂，所述辅助佐剂选自第2型佐剂（例如明胶和/或MF59）、第1型佐剂和/或平衡佐剂。包含该佐剂组合物的疫苗包括编码一种或多种抗原蛋白的核酸；蛋白质或肽；糖蛋白；多糖（例如碳水化合物）；融合蛋白；脂质；糖脂；多糖碳水化合物和蛋白质的肽类模拟物；糖蛋白-蛋白质结合物；细胞或其提取物；死细胞或其提取物；肿瘤细胞或其提取物；病毒颗粒（例如弱毒病毒颗粒或病毒成分）；过敏原或其混合物。
• Immunomodulatory compositions
  申请人：Watson Ann Alison

  公开号：US20070155814A1

  公开（公告）日：2007-07-05

  Isolated immunomodulatory (e.g. immunostimulatory) polyhydroxlated pyrrolizidine compounds having the formula are disclosed. In these compounds R is selected from hydrogen, straight or branched, unsubstituted or substituted, saturated or unsaturated acyl, alkyl (e.g. cycloalkyl), alkenyl, alkynyl and aryl groups. The compounds are useful in therapy and prophylaxis, including increasing the Th1:Th2 response ratio, hemorestoration, alleviation of immunosuppression, cytokine stimulation, treatment of proliferative disorders (e.g. cancer), vaccination, stimulation of the innate immune response and boosting of the activity of endogenous NK cells.

  本发明公开了具有以下式的孤立免疫调节（例如免疫刺激）多羟基吡咯烷化合物。在这些化合物中，R从氢，直链或支链，未取代或取代，饱和或不饱和酰基，烷基（例如环烷基），烯基，炔基和芳基中选择。这些化合物在治疗和预防中很有用，包括增加Th1：Th2反应比，血液恢复，减轻免疫抑制，细胞因子刺激，治疗增殖性疾病（例如癌症），接种，刺激先天免疫反应和提高内源性NK细胞的活性。
• IMMUNOMODULATORY ALKALOIDS
  申请人：Nash Robert James

  公开号：US20090117083A1

  公开（公告）日：2009-05-07

  Immunotherapy comprises administration of an alkaloid at a dose sufficient to induce IL-2 production in dendritic cells in a patient. The alkaloid induces the production of IL-2 in dendritic cells. The alkaloids need not be naturally occurring, and may be synthetic analogues or derivatives of naturally occurring counterparts. Such analogues or derivatives are preferably pharmaceutically acceptable analogues, salts, isomers or derivatives as herein defined. However, preferred alkaloids are phytochemicals. Such phytochemicals may be isolated from natural sources or synthesised in vitro. Particularly preferred are alkaloids is selected from piperidine alkaloids; pyrrolin alkaloids; pyrrolidine alkaloids; pyrolizidine alkaloids: indolizidine alkaloids and nortropane alkaloids.

  免疫疗法包括在患者体内以足够剂量给予一种生物碱，以诱导树突状细胞产生IL-2。这种生物碱会引起树突状细胞产生IL-2。这些生物碱不一定是天然存在的，也可以是天然存在的衍生物或合成类似物。这些类似物或衍生物最好是药学上可接受的类似物、盐、异构体或衍生物，如本文所定义。然而，最好的生物碱是植物化学物质。这些植物化学物质可以从天然来源中分离出来，也可以在体外合成。特别优选的生物碱包括吡啶生物碱、吡咯烷生物碱、吡咯烷生物碱、吡咯菊烷生物碱、吲哚菊烷生物碱和诺滕烷生物碱。
• 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.