(1,2:3,4-di-O-isopropylidene-6-deoxyazido)-α-D-galactopyranose | 212484-29-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氧吡喃
• 英文名称: (1,2:3,4-di-O-isopropylidene-6-deoxyazido)-α-D-galactopyranose
• 英文别名: (1S,2R,8R,9S)-8-(azidomethyl)-4,4,11,11-tetramethyl-3,5,7,10,12-pentaoxatricyclo[7.3.0.02,6]dodecane
• CAS: 212484-29-2
• 化学式: C₁₂H₁₉N₃O₅
• 分子量: 285.3
• InChiKey: KIBLVBPHQCVUFG-CYNREMDZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  60.5
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (1,2:3,4-di-O-isopropylidene-6-deoxyazido)-α-D-galactopyranose 在 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以97%的产率得到1-[(3aR,5aS,8aS,8bR)-2,2,7,7-四甲基四氢-3aH-二[1,3]二氧杂环戊并[4,5-b:4',5'-d]吡喃-5-基]甲胺
  参考文献：
  名称：

  Synthesis and Evaluation as Prodrugs of Hydrophilic Carbamate Ester Analogues of Resveratrol

  摘要：

  Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is an unfulfilled promise for health care: its exploitation is hindered by rapid conjugative metabolism in enterocytes and hepatocytes; low water solubility is a serious practical problem. To advantageously modify the physicochemical properties of the compound we have developed prodrugs in which all or part of the hydroxyl groups are linked via an N-monosubstituted carbamate ester bond to promoieties derived from glycerol or galactose, conferring higher water solubility. Kinetic studies of hydrolysis in aqueous solutions and in blood indicated that regeneration of resveratrol takes place in an appropriate time frame for delivery via oral administration. Despite their hydrophilicity some of the synthesized compounds were absorbed in the gastrointestinal tract of rats. In these cases the species found in blood after administration of a bolus consisted mainly of partially deprotected resveratrol derivatives and of the products of their glucuronidation, thus providing proof-of-principle evidence of behavior as prodrugs. The soluble compounds largely reached the lower intestinal tract. Upon administration of resveratrol, the major species found in this region was dihydroresveratrol, produced by enzymes of the intestinal flora. In experiments with a fully protected (trisubstituted) deoxygalactose containing prodrug, the major species were the prodrug itself and partially deprotected derivatives, along with small amounts of dihydroresveratrol. We conclude that the N-monosubstituted carbamate moiety is suitable for use in prodrugs of polyphenols.

  DOI：

  10.1021/acs.molpharmaceut.5b00464
• 作为产物：
  描述：

  (1,2:3,4-di-O-isopropylidene-6-O-(p-toluenesulfonate))-α-D-galactopyranose 在 sodium azide 作用下， 以 二甲基亚砜 为溶剂， 反应 1.5h， 以93%的产率得到(1,2:3,4-di-O-isopropylidene-6-deoxyazido)-α-D-galactopyranose
  参考文献：
  名称：

  Synthesis and Evaluation as Prodrugs of Hydrophilic Carbamate Ester Analogues of Resveratrol

  摘要：

  Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is an unfulfilled promise for health care: its exploitation is hindered by rapid conjugative metabolism in enterocytes and hepatocytes; low water solubility is a serious practical problem. To advantageously modify the physicochemical properties of the compound we have developed prodrugs in which all or part of the hydroxyl groups are linked via an N-monosubstituted carbamate ester bond to promoieties derived from glycerol or galactose, conferring higher water solubility. Kinetic studies of hydrolysis in aqueous solutions and in blood indicated that regeneration of resveratrol takes place in an appropriate time frame for delivery via oral administration. Despite their hydrophilicity some of the synthesized compounds were absorbed in the gastrointestinal tract of rats. In these cases the species found in blood after administration of a bolus consisted mainly of partially deprotected resveratrol derivatives and of the products of their glucuronidation, thus providing proof-of-principle evidence of behavior as prodrugs. The soluble compounds largely reached the lower intestinal tract. Upon administration of resveratrol, the major species found in this region was dihydroresveratrol, produced by enzymes of the intestinal flora. In experiments with a fully protected (trisubstituted) deoxygalactose containing prodrug, the major species were the prodrug itself and partially deprotected derivatives, along with small amounts of dihydroresveratrol. We conclude that the N-monosubstituted carbamate moiety is suitable for use in prodrugs of polyphenols.

  DOI：

  10.1021/acs.molpharmaceut.5b00464

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...
• Modified Proteins
  申请人：Behrens Carsten

  公开号：US20080108557A1

  公开（公告）日：2008-05-08

  A method of conjugating peptides and proteins by means of glycosyltransferase is provided.

  提供了一种通过糖基转移酶结合肽和蛋白质的方法。
• MODIFIED PROTEINS
  申请人：Novo Nordisk Health Care AG

  公开号：EP1797192A1

  公开（公告）日：2007-06-20
• [EN] MODIFIED PROTEINS<br/>[FR] PROTEINES MODIFIEES
  申请人：NOVO NORDISK AS

  公开号：WO2006035057A1

  公开（公告）日：2006-04-06

  A method of conjugating peptides and proteins by means of glycosyltransferase is provided.
• Synthesis and Evaluation as Prodrugs of Hydrophilic Carbamate Ester Analogues of Resveratrol
  作者：Michele Azzolini、Andrea Mattarei、Martina La Spina、Ester Marotta、Mario Zoratti、Cristina Paradisi、Lucia Biasutto

  DOI：10.1021/acs.molpharmaceut.5b00464

  日期：2015.9.8

  Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is an unfulfilled promise for health care: its exploitation is hindered by rapid conjugative metabolism in enterocytes and hepatocytes; low water solubility is a serious practical problem. To advantageously modify the physicochemical properties of the compound we have developed prodrugs in which all or part of the hydroxyl groups are linked via an N-monosubstituted carbamate ester bond to promoieties derived from glycerol or galactose, conferring higher water solubility. Kinetic studies of hydrolysis in aqueous solutions and in blood indicated that regeneration of resveratrol takes place in an appropriate time frame for delivery via oral administration. Despite their hydrophilicity some of the synthesized compounds were absorbed in the gastrointestinal tract of rats. In these cases the species found in blood after administration of a bolus consisted mainly of partially deprotected resveratrol derivatives and of the products of their glucuronidation, thus providing proof-of-principle evidence of behavior as prodrugs. The soluble compounds largely reached the lower intestinal tract. Upon administration of resveratrol, the major species found in this region was dihydroresveratrol, produced by enzymes of the intestinal flora. In experiments with a fully protected (trisubstituted) deoxygalactose containing prodrug, the major species were the prodrug itself and partially deprotected derivatives, along with small amounts of dihydroresveratrol. We conclude that the N-monosubstituted carbamate moiety is suitable for use in prodrugs of polyphenols.