(1S,3'R,4'S,5'R,6'R)-3',4',5'-tris(benzyloxy)-6′-((benzyloxy)-methyl)-3′,4′,5′,6′-tetrahydro-3H-spiro[2-benzofuran-1,2′-pyran]-6-carbaldehyde | 903566-44-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异香豆素
• 英文名称: (1S,3'R,4'S,5'R,6'R)-3',4',5'-tris(benzyloxy)-6′-((benzyloxy)-methyl)-3′,4′,5′,6′-tetrahydro-3H-spiro[2-benzofuran-1,2′-pyran]-6-carbaldehyde
• 英文别名: 1,1-anhydro-1-C-[5-formyl-2-(hydroxymethyl)phenyl]-2,3,4,6-tetra-O-benzyl-β-D-glucopyranose；(3S,3'R,4'S,5'R,6'R)-3',4',5'-tris(phenylmethoxy)-6'-(phenylmethoxymethyl)spiro[1H-2-benzofuran-3,2'-oxane]-5-carbaldehyde
• CAS: 903566-44-9
• 化学式: C₄₂H₄₀O₇
• 分子量: 656.775
• InChiKey: SYLFLNHXVWMUPH-DJLQKWJRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  49
• 可旋转键数：
  14
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  72.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (1S,3'R,4'S,5'R,6'R)-3',4',5'-tris(benzyloxy)-6′-((benzyloxy)-methyl)-3′,4′,5′,6′-tetrahydro-3H-spiro[2-benzofuran-1,2′-pyran]-6-carbaldehyde 在 盐酸 、 三乙基硅烷 、 三氟化硼乙醚 、 氢气 、 palladium(II) hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 1.0h， 生成 1,1-anhydro-1-C-[5-(4-isopropylphenyl)methyl-2-(hydroxymethyl)phenyl]-β-D-glucopyranose
  参考文献：
  名称：

  Discovery of Tofogliflozin, a Novel C-Arylglucoside with an O-Spiroketal Ring System, as a Highly Selective Sodium Glucose Cotransporter 2 (SGLT2) Inhibitor for the Treatment of Type 2 Diabetes

  摘要：

  Inhibition of sodium glucose cotransporter 2 (SGLT2) has been proposed as a novel therapeutic approach to treat type 2 diabetes. In our efforts to discover novel inhibitors of SGLT2, we first generated a 3D pharmacophore model based on the superposition of known inhibitors. A search of the Cambridge Structural Database using a series of pharmacophore queries led to the discovery of an O-spiroketal C-arylglucoside scaffold. Subsequent chemical examination combined with computational modeling resulted in the identification of the clinical candidate 16d (CSG452, tofogliflozin), which is currently under phase III clinical trials.

  DOI：

  10.1021/jm300884k
• 作为产物：
  描述：

  [(3S,3'R,4'S,5'R,6'R)-3',4',5'-tris(phenylmethoxy)-6'-(phenylmethoxymethyl)spiro[1H-2-benzofuran-3,2'-oxane]-5-yl]methanol 在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 以33%的产率得到(1S,3'R,4'S,5'R,6'R)-3',4',5'-tris(benzyloxy)-6′-((benzyloxy)-methyl)-3′,4′,5′,6′-tetrahydro-3H-spiro[2-benzofuran-1,2′-pyran]-6-carbaldehyde
  参考文献：
  名称：

  头孢格列嗪可扩展合成方法的开发

  摘要：

  描述了一种高效，可扩展的抗糖尿病药物tofogliflozin（1）的合成，该药物被确定为高选择性钠葡萄糖共转运蛋白2（SGLT2）抑制剂。合成1的关键因素是选择专门设计的保护基，该保护基在保护，化学选择性活化和晶体纯化中起着战略性作用。通过开发和优化的方法，无需任何柱色谱法就可以以十克规模制备1。

  DOI：

  10.1021/acs.joc.5b02734

文献信息

• Spiroketal derivatives and use thereof as diabetic medicine
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：US07767651B2

  公开（公告）日：2010-08-03

  The present invention provides a compound of Formula (I): wherein R1, R2, R3 and R4 are each independently selected from a hydrogen atom, an optionally substituted C1-C6 alkyl group, an optionally substituted C7-C14 aralkyl group and —C(═O)Rx; Rx represents an optionally substituted C1-C6 alkyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, an optionally substituted C1-C6 alkoxy group or —NReRf; Ar1 represents an optionally substituted aromatic carbocyclic ring or an optionally mono-substituted aromatic heterocyclic ring; Q represents —(CH2)m-(L)p- or -(L)p-(CH2)m—; m represents an integer selected from 0 to 2, n represents an integer selected from 1 and 2, and p represents an integer selected from 0 and 1; L represents —O—, —S— or —NR5—; and A represents an optionally substituted aryl group or an optionally substituted heteroaryl group, a prodrug thereof and a pharmaceutically acceptable salt thereof, as well as a pharmaceutical preparation or pharmaceutical composition comprising such a compound.

  本发明提供了一种化合物，其化学式为(I)：其中R1、R2、R3和R4各自独立地选择自氢原子、可选取代的C1-C6烷基、可选取代的C7-C14芳基烷基和—C(═O)Rx；Rx代表可选取代的C1-C6烷基、可选取代的芳基、可选取代的杂芳基、可选取代的C1-C6烷氧基或—NReRf；Ar1代表可选取代的芳香环烷基或可选取代的单取代芳香杂环烷基；Q代表—(CH2)m-(L)p-或-(L)p-(CH2)m—；m代表0至2的整数，n代表1或2的整数，p代表0或1的整数；L代表—O—、—S—或—NR5—；A代表可选取代的芳基或可选取代的杂芳基，其前体、其药学上可接受的盐以及包含该化合物的制药制备或制药组合物。
• SPIROKETAL DERIVATIVES AND USE THEREOF AS DIABETIC MEDICINE
  申请人：Kobayashi Takamitsu

  公开号：US20090030006A1

  公开（公告）日：2009-01-29

  The present invention provides a compound of Formula (I): wherein R 1 , R 2 , R 3 and R 4 are each independently selected from a hydrogen atom, an optionally substituted C 1 -C 6 alkyl group, an optionally substituted C 7 -C 14 aralkyl group and —C(═O)Rx; Rx represents an optionally substituted C 1 -C 6 alkyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, an optionally substituted C 1 -C 6 alkoxy group or —NReRf; Ar 1 represents an optionally substituted aromatic carbocyclic ring or an optionally mono-substituted aromatic heterocyclic ring; Q represents —(CH 2 ) m -(L) p - or -(L) p -(CH 2 ) m —; m represents an integer selected from 0 to 2, n represents an integer selected from 1 and 2, and p represents an integer selected from 0 and 1; L represents —O—, —S— or —NR 5 —; and A represents an optionally substituted aryl group or an optionally substituted heteroaryl group, a prodrug thereof and a pharmaceutically acceptable salt thereof, as well as a pharmaceutical preparation or pharmaceutical composition comprising such a compound.

  本发明提供了一种化合物，其化学式为(I)，其中R1、R2、R3和R4各自独立地选自氢原子、可选取代的C1-C6烷基、可选取代的C7-C14芳基烷基和—C(═O)Rx；Rx代表可选取代的C1-C6烷基、可选取代的芳基、可选取代的杂环芳基、可选取代的C1-C6烷氧基或—NReRf；Ar1代表可选取代的芳香环烷基或可选单取代的芳香杂环烷基；Q代表—(CH2)m-(L)p-或-(L)p-(CH2)m—；m代表选自0至2的整数，n代表选自1和2的整数，p代表选自0和1的整数；L代表—O—、—S—或—NR5—；A代表可选取代的芳基或可选取代的杂环芳基，以及该化合物的前药和药学上可接受的盐，以及包含该化合物的制药制备或制药组合物。
• SPIROKETAL DERIVATIVE AND USE THEREOF AS DIABETIC MEDICINE
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA

  公开号：EP1852439B1

  公开（公告）日：2016-03-23
• WO2006080421A1
  申请人：——

  公开号：——

  公开（公告）日：——
• J. Med. Chem. 2012, 55, 7828-7840
  作者：

  DOI：——

  日期：——