2-O-benzyl-3,4-di-O-p-methoxybenzyl-D-α/β-xylopyranosyl dimethyl phosphite | 290811-02-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-O-benzyl-3,4-di-O-p-methoxybenzyl-D-α/β-xylopyranosyl dimethyl phosphite
• 英文别名: 2-O-benzyl-3,4-bis-O-(p-methoxybenzyl)-α-D-xylopyranosyl dimethyl phosphite；[(3R,4S,5R)-4,5-bis[(4-methoxyphenyl)methoxy]-3-phenylmethoxyoxan-2-yl] dimethyl phosphite
• CAS: 290811-02-8
• 化学式: C₃₀H₃₇O₉P
• 分子量: 572.592
• InChiKey: PZCZVIMQFHJSTR-XDRPPRNFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  40
• 可旋转键数：
  15
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  83.1
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-O-benzyl-3,4-di-O-p-methoxybenzyl-D-α/β-xylopyranosyl dimethyl phosphite 在 silver perchlorate 、 三氟乙酸 、 zinc(II) chloride 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 甲苯 为溶剂， 反应 4.33h， 生成 1-O-[(3'R,4SR)-3-hydroxytetrahydrofuran-4-yl] 2-O-benzyl-α-D-xylopyranose
  参考文献：
  名称：

  Xylopyranoside-based agonists of d-myo-inositol 1,4,5-trisphosphate receptors: synthesis and effect of stereochemistry on biological activity

  摘要：

  The synthesis of a series of tetrahydrofuranyl alpha- and beta -xylopyranoside trisphosphates, designed by excision of three motifs of adenophostin A is reported. The synthetic route features improved preparations of allyl alpha -D-xylopyranoside and its 2-O-benzyl ether, and gives access to four diastereoisomeric trisphosphates, which show a range of abilities to mobilise Ca2+ from the intracellular stores of hepatocytes. A comparison of the potencies of the four trisphosphates provides useful information relating to the effects of stereochemical variation on the recognition of carbohydrate-based trisphosphates by D-myo-inositol 1,4,5-trisphosphate receptors. 1-O-[(3 'S,4 'R)-3-hydroxytetrahydrofuran-4-yl] alpha -D-xylopyranoside 3,4,3 ' -trisphosphate (8) is the most active member of the series with a potency close to Ins(1,4,5)P-3; a beta -linked analogue, 1-O-[(3 'R,4 'S)-3-hydroxytetrahydrofuran-4-yl] beta -D-xylopranoside 3,4,3 ' -trisphosphate, is ca. 20-fold weaker than Ins(1,4,5)P-3, and the other compounds are much less active. While no compound attained a potency close to that of adenophostin A, we believe that 8 represents the minimal structure for potent Ca2+-releasing activity in this type of carbohydrate-based analogue. (C) 2001 Elsevier Science I,td. All rights reserved.

  DOI：

  10.1016/s0008-6215(01)00067-2
• 作为产物：
  描述：

  D-吡喃木糖 在 palladium dichloride 吡啶 、 四氮唑 、 盐酸 、 sodium hydroxide 、 sodium hydride 、 对甲苯磺酸 、 乙酰氯 作用下， 以 四氢呋喃 、 甲醇 、 氘代氯仿 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 37.33h， 生成 2-O-benzyl-3,4-di-O-p-methoxybenzyl-D-α/β-xylopyranosyl dimethyl phosphite
  参考文献：
  名称：

  Xylopyranoside-based agonists of d-myo-inositol 1,4,5-trisphosphate receptors: synthesis and effect of stereochemistry on biological activity

  摘要：

  The synthesis of a series of tetrahydrofuranyl alpha- and beta -xylopyranoside trisphosphates, designed by excision of three motifs of adenophostin A is reported. The synthetic route features improved preparations of allyl alpha -D-xylopyranoside and its 2-O-benzyl ether, and gives access to four diastereoisomeric trisphosphates, which show a range of abilities to mobilise Ca2+ from the intracellular stores of hepatocytes. A comparison of the potencies of the four trisphosphates provides useful information relating to the effects of stereochemical variation on the recognition of carbohydrate-based trisphosphates by D-myo-inositol 1,4,5-trisphosphate receptors. 1-O-[(3 'S,4 'R)-3-hydroxytetrahydrofuran-4-yl] alpha -D-xylopyranoside 3,4,3 ' -trisphosphate (8) is the most active member of the series with a potency close to Ins(1,4,5)P-3; a beta -linked analogue, 1-O-[(3 'R,4 'S)-3-hydroxytetrahydrofuran-4-yl] beta -D-xylopranoside 3,4,3 ' -trisphosphate, is ca. 20-fold weaker than Ins(1,4,5)P-3, and the other compounds are much less active. While no compound attained a potency close to that of adenophostin A, we believe that 8 represents the minimal structure for potent Ca2+-releasing activity in this type of carbohydrate-based analogue. (C) 2001 Elsevier Science I,td. All rights reserved.

  DOI：

  10.1016/s0008-6215(01)00067-2

文献信息

• Synthesis of adenophostin A and congeners modified at glucose
  作者：Rachel D. Marwood、Andrew M. Riley、David J. Jenkins、Barry V. L. Potter

  DOI：10.1039/b001386m

  日期：——

  A convergent route is described to the super-potent 1D-myo-inositol 1,4,5-trisphosphate receptor agonist adenophostin A (2) and analogues 5 and 7, in which the glucose bisphosphate unit is replaced by corresponding xylose bisphosphate and mannose bisphosphate units respectively. Adenosine was converted into its 2′,3′-O-p-methoxybenzylidene derivative 8ab, which was selectively N6-dimethoxytritylated by a transient protection method. 5′-O-Benzylation followed by reductive acetal cleavage gave, after separation from its 3′-O-p-methoxybenzyl isomer, the versatile glycosyl acceptor 5′-O-benzyl-N6-dimethoxytrityl-2′-O-p-methoxybenzyladenosine 13. Coupling of 13 with selectively protected glucopyranosyl, xylopyranosyl or mannopyranosyl dimethyl phosphites gave the required 3′-O-α-pyranosyl adenosine derivatives. Acidic hydrolysis gave corresponding N6-unprotected triols which were phosphitylated using bis(benzyloxy)(diisopropylamino)phosphine and imidazolium triflate without further N6-protection. Deprotection gave the target trisphosphates 2, 5 and 7. Synthetic adenophostin A (2) was identical with a sample of natural material in all respects. Analogues 5 and 7 will be useful for structure–activity studies on the adenophostins.

  描述了超强效 1D-肌醇 1,4,5-三磷酸受体激动剂腺磷蛋白 A (2) 以及类似物 5 和 7 的收敛途径，其中葡萄糖二磷酸单元被相应的木糖二磷酸和甘露糖二磷酸取代分别为单位。腺苷转化为其2',3'-O-对甲氧基亚苯亚甲基衍生物8ab，并通过瞬时保护方法选择性地N6-二甲氧基三苯甲基化。 5'-O-苄基化，然后还原缩醛裂解，在与 3'-O-对甲氧基苄基异构体分离后，得到多功能糖基受体 5'-O-苄基-N6-二甲氧基三苯甲基-2'-O-对甲氧基苄基腺苷 13。 13 具有选择性保护的吡喃葡萄糖基、吡喃木糖基或吡喃甘露糖基亚磷酸二甲酯得到所需的3'-O-α-吡喃糖基腺苷衍生物。酸性水解得到相应的N6-未保护的三醇，将其使用双(苄氧基)(二异丙氨基)膦和三氟甲磺酸咪唑鎓进行亚磷酸化，无需进一步的N6-保护。脱保护得到目标三磷酸2、5和7。合成的腺苷磷汀A (2)在所有方面与天然材料样品相同。类似物 5 和 7 可用于腺苷磷酸酯的结构-活性研究。