5S-azido-5-deoxy-1,2:3,4-di-O-isopropylidene-(+)-proto-quercitol | 1157852-11-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5S-azido-5-deoxy-1,2:3,4-di-O-isopropylidene-(+)-proto-quercitol
• 英文别名: (1S,2S,6S,7S,9R)-7-azido-4,4,11,11-tetramethyl-3,5,10,12-tetraoxatricyclo[7.3.0.02,6]dodecane
• CAS: 1157852-11-3
• 化学式: C₁₂H₁₉N₃O₄
• 分子量: 269.301
• InChiKey: SWQPXDUUCPLXIH-SVSWQMSJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  51.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5S-azido-5-deoxy-1,2:3,4-di-O-isopropylidene-(+)-proto-quercitol 在 lithium aluminium tetrahydride 、 sodium cyanoborohydride 、 溶剂黄146 、 三氟乙酸 作用下， 以 甲醇 为溶剂， 反应 26.0h， 生成 N-(4-hydroxybenzyl)-epi-aminoquercitol
  参考文献：
  名称：

  N-Arylmethylaminoquercitols, a new series of effective antidiabetic agents having α-glucosidase inhibition and antioxidant activity

  摘要：

  A new series of N-arylalkylaminoquercitols were synthesized by reductive amination of aminoquercitol bisacetonide 5 and a variety of aryl aldehydes. The targeted N-substituted aminoquercitols having phenolic moiety (7a-7c) displayed significantly enhanced alpha-glucosidase inhibition, which is 26-32 times more potent than that of the unmodified aminoquercitol 6. In addition, compounds 7a-7c also retained antioxidant activity with relatively more pronounced potency than their original phenolics. This recent finding suggests an approach to develop effective antidiabetic agents by incorporating antioxidative moiety into aminocyclitol core structure. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.04.033
• 作为产物：
  描述：

  原栎醇 在 4-二甲氨基吡啶 、 sodium azide 、 15-冠醚-5 、 对甲苯磺酸 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.0h， 生成 5S-azido-5-deoxy-1,2:3,4-di-O-isopropylidene-(+)-proto-quercitol
  参考文献：
  名称：

  伏格列波糖启发的新型强力α-葡萄糖苷酶抑制剂N-1,3-二羟丙基氨基环糖醇的合成

  摘要：

  伏格列波糖（一种N-1,3-二羟丙基氨基环糖醇）已广泛用作糖尿病治疗的有效α-葡萄糖苷酶抑制剂。已经进行了多种尝试，以通过各种氨基环糖醇和丙烷-1，3-二醇的偶联来合成紧密相关的类似物。然而，它们大多数显示出较弱的抑制作用或没有抑制作用。在这次交流中，我们使用（+）-原-槲皮醇（1）作为环糖醇核心结构合成了一对新的N-1,3-二羟丙基氨基环糖醇（10和11）。新合成的化合物显示出强效的大鼠肠道α-葡萄糖苷酶，尤其是针对麦芽糖酶的酶，其IC50值为亚微摩尔。随后对11抑制作用机理的研究表明了对麦芽糖酶和蔗糖酶的竞争方式。通过对接研究详细阐述了这些化合物的有效抑制作用，其中它们与活性位点中关键氨基酸残基的结合曲线与伏格列波糖相似。因此，将丙烷-1,3-二醇部分引入合适的环己烷核心结构（如氨基槲皮醇）将是发现一系列新的有效α-葡萄糖苷酶抑制剂的潜在途径。

  DOI：

  10.1016/j.carres.2016.04.014

文献信息

• (+)-proto-Quercitol, a natural versatile chiral building block for the synthesis of the α-glucosidase inhibitors, 5-amino-1,2,3,4-cyclohexanetetrols
  作者：Sumrit Wacharasindhu、Wisuttaya Worawalai、Wimolpun Rungprom、Preecha Phuwapraisirisan

  DOI：10.1016/j.tetlet.2009.02.153

  日期：2009.5

  diastereomerically pure 5-amino-1,2,3,4-cyclohexanetetrols (6 and 11) and quercitol derivatives from naturally available (+)-proto-quercitol (1) is described. The stereochemistry of 1 is perfectly set up for regioselective protection of the hydroxy group which was further functionalized into the target aminocyclitol in a straightforward manner. The present approach provides a protocol for preparing aminocyclitols

  描述了由天然可得的（+）-原-槲皮醇（1）有效合成非对映体纯的5-氨基-1,2,3,4-环己烷四醇（6和11）和槲皮醇衍生物。立体化学1的建立是为了对羟基进行区域选择性保护，该羟基以直接的方式进一步官能化成目标氨基环糖醇。本方法提供了用于大量制备氨基环醇的方案。另外，使用改进的Mosher方法解决了（+）-原-槲皮醇的绝对立体化学。在合成的氨基环糖醇中，有11种可能通过IC抑制α-葡萄糖苷酶50值12.5μM，其比标准降糖药，阿卡波糖的大45倍的®。
• Amine-linked diquercitols as new α-glucosidase inhibitors
  作者：Wisuttaya Worawalai、Sumrit Wacharasindhu、Preecha Phuwapraisirisan

  DOI：10.1016/j.bmcl.2014.09.064

  日期：2014.12

  Two new diastereomeric amine-linked diquercitols 7 and 8 were synthesized by reductive amination of ketoquercitol 4 and epimeric aminoquercitols 3 and 6. The ketone and amines were successfully prepared, without the formation of byproducts, from naturally available (+)-proto-quercitol (1). The amine-linked diquercitols showed inhibitory effect against alpha-glucosidases with more pronounced potency than their original aminoquercitol monomers. (C) 2014 Elsevier Ltd. All rights reserved.
• N-Arylmethylaminoquercitols, a new series of effective antidiabetic agents having α-glucosidase inhibition and antioxidant activity
  作者：Wisuttaya Worawalai、Sumrit Wacharasindhu、Preecha Phuwapraisirisan

  DOI：10.1016/j.bmcl.2015.04.033

  日期：2015.6

  A new series of N-arylalkylaminoquercitols were synthesized by reductive amination of aminoquercitol bisacetonide 5 and a variety of aryl aldehydes. The targeted N-substituted aminoquercitols having phenolic moiety (7a-7c) displayed significantly enhanced alpha-glucosidase inhibition, which is 26-32 times more potent than that of the unmodified aminoquercitol 6. In addition, compounds 7a-7c also retained antioxidant activity with relatively more pronounced potency than their original phenolics. This recent finding suggests an approach to develop effective antidiabetic agents by incorporating antioxidative moiety into aminocyclitol core structure. (C) 2015 Elsevier Ltd. All rights reserved.
• Voglibose-inspired synthesis of new potent α-glucosidase inhibitors N-1,3-dihydroxypropylaminocyclitols
  作者：Wisuttaya Worawalai、Pornthep Sompornpisut、Sumrit Wacharasindhu、Preecha Phuwapraisirisan

  DOI：10.1016/j.carres.2016.04.014

  日期：2016.6

  (+)-proto-quercitol (1) as a cyclitol core structure. The newly synthesized compounds revealed potent rat intestinal α-glucosidases, particularly against maltase, with IC50 values at submicromolar. Subsequent study on mechanisms underlying the inhibition of 11 indicated the competitive manner towards maltase and sucrase. The potent inhibition of these compounds was elaborated by docking study, in which their binding

  伏格列波糖（一种N-1,3-二羟丙基氨基环糖醇）已广泛用作糖尿病治疗的有效α-葡萄糖苷酶抑制剂。已经进行了多种尝试，以通过各种氨基环糖醇和丙烷-1，3-二醇的偶联来合成紧密相关的类似物。然而，它们大多数显示出较弱的抑制作用或没有抑制作用。在这次交流中，我们使用（+）-原-槲皮醇（1）作为环糖醇核心结构合成了一对新的N-1,3-二羟丙基氨基环糖醇（10和11）。新合成的化合物显示出强效的大鼠肠道α-葡萄糖苷酶，尤其是针对麦芽糖酶的酶，其IC50值为亚微摩尔。随后对11抑制作用机理的研究表明了对麦芽糖酶和蔗糖酶的竞争方式。通过对接研究详细阐述了这些化合物的有效抑制作用，其中它们与活性位点中关键氨基酸残基的结合曲线与伏格列波糖相似。因此，将丙烷-1,3-二醇部分引入合适的环己烷核心结构（如氨基槲皮醇）将是发现一系列新的有效α-葡萄糖苷酶抑制剂的潜在途径。