(2R,3R,4S,6R)-2,3:4,5-bis(isopropylidenedioxy)-1-cyclohexanone | 415726-81-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2R,3R,4S,6R)-2,3:4,5-bis(isopropylidenedioxy)-1-cyclohexanone
• 英文别名: 1,2:3,4-di-O-isopropylidene-5-cyclohexanone；(1S,2R,6R,9R)-4,4,11,11-tetramethyl-3,5,10,12-tetraoxatricyclo[7.3.0.02,6]dodecan-7-one
• CAS: 415726-81-7
• 化学式: C₁₂H₁₈O₅
• 分子量: 242.272
• InChiKey: COXSXIHCKVBZHZ-KATARQTJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R,3R,4S,6R)-2,3:4,5-bis(isopropylidenedioxy)-1-cyclohexanone 在 吡啶 、 正丁基锂 、 溴 、 4-甲基苯磺酸吡啶 、 碳酸氢钠 作用下， 以 四氢呋喃 、 甲醇 、 四氯化碳 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 88.5h， 生成 2,6-di-O-benzoyl-3,4-O-isopropylidene-5a-carba-β-L-arabino-hex-5(5a)-enopyranosyl bromide
  参考文献：
  名称：

  Concise syntheses of potent chaperone drug candidates, N-octyl-4-epi-β-valinenamine (NOEV) and its 6-deoxy derivative, from (+)-proto-quercitol

  摘要：

  Described are the efficient syntheses of beta-galactose-type unsaturated carbasugar amine, N-octyl-4-epi-beta-valienamine (1a, NOEV) and 6-deoxy NOEV (12), starting from (+)-proto-quercitol (2), which is readily provided by the bioconversion of myo-inositol. NOEV is a potent chemical chaperone drug candidate for G(M1)-gangliosidosis. An intermediate alkadiene benzoate was prepared from 2 in five steps, with the key step being a Wittig reaction with an enol ester. The 6-deoxy derivative 12 was conveniently synthesized from the versatile intermediate dibromo compound 6, which was also an intermediate in the synthesis of NOEV. Enzyme inhibition assays demonstrated that 12 possessed stronger inhibitory activity than the parent 1a, suggesting that the C-6 position of the 4-epi-beta-valienamine-type inhibitor could have hydrophobic interactions at the beta-galactosidase active site residues. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.carres.2012.12.010
• 作为产物：
  描述：

  原栎醇 在 D(+)-10-樟脑磺酸 、 三氧化硫吡啶 、 二甲基亚砜 、 三乙胺 作用下， 以 丙酮 为溶剂， 反应 23.5h， 生成 (2R,3R,4S,6R)-2,3:4,5-bis(isopropylidenedioxy)-1-cyclohexanone
  参考文献：
  名称：

  Transformation of quercitols into 4-methylenecyclohex-5-ene-1,2,3-triol derivatives, precursors for the chemical chaperones N-octyl-4-epi-β-valienamine (NOEV) and N-octyl-β-valienamine (NOV)

  摘要：

  (+)-原儿茶糖苷醇(1)和(-)-威博儿茶糖苷醇(2)，这两种糖苷均可以通过肌醇的生物转化简便制备，成功转化为了相应的4-甲基环己-5-烯-1,2,3-三醇衍生物。研究证明，这些化合物在保留其构型的情况下，适合作为具有生物活性的氨基糖（如强效化学伴侣药物候选物N-辛基-4-表-β-戊吡胺醇(3)和N-辛基-β-戊吡胺醇(4)）的前体。 (以上译文仅供参考，英文原文版权为2011 Elsevier Ltd.所有，保留所有权利。)

  DOI：

  10.1016/j.bmcl.2011.09.067

文献信息

• 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。
• (+)-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®。
• Quercitylcinnamates, a new series of antidiabetic bioconjugates possessing α-glucosidase inhibition and antioxidant
  作者：Eakkaphon Rattanangkool、Preecha Kittikhunnatham、Thanakorn Damsud、Sumrit Wacharasindhu、Preecha Phuwapraisirisan

  DOI：10.1016/j.ejmech.2013.05.047

  日期：2013.8

  Antidiabetic agents possessing dual functions, alpha-glucosidase inhibition and antioxidant, have been accepted to be more useful than currently used antidiabetic drugs because they not only suppress hyperglycemia but also prevent risk of complications. Herein, we design antidiabetic bioconjugates comprising of (+)-proto-quercitol as a glucomimic and cinnamic analogs as antioxidant moieties. Fifteen quercitylcinnamates were synthesized by direct coupling through ester bond in the presence of DCC and DMAP. Particular quercityl esters 6a, 7a and 8a selectively inhibited rat intestinal maltase and sucrose 4 -6 times more potently than their parents 6, 7 and 8. Of synthesized bioconjugates, 6a was the most potent inhibitor against maltase and sucrose with IC50 values of 531 and 43.65 mu M, respectively. Of interest, its inhibitory potency toward maltase was 6 times greater than its parent, caffeic acid (6), while its radical scavenging (SC50 0.11 mM) was comparable to that of commercial antioxidant BHA. Subsequent investigation on mechanism underlying inhibitory effect of 6a indicated that it blocked maltase and sucrose functions by mixed inhibition through competitive and noncompetitive manners. (C) 2013 Elsevier Masson SAS. All rights reserved.
• 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.
• SYNTHESIS OF 1- AND 3-C-(AMINOMETHYL)-1,2,3,4,5-CYCLOHEXANEPENTOLS FROM (+)-epi-QUERCITOL1
  作者：Seiichiro Ogawa、Hiroshi Aoyama、Yoji Tezuka

  DOI：10.1081/car-100108284

  日期：——

  Oxidation of three di-O-isopropylidene derivatives 2a-4a, newly derived from (+)-epi-quercitol (1), with acetic anhydride in DMSO gave the corresponding ketones 5-7, which underwent aldol-type condensation with nitromethane under basic conditions to give selectively the protected derivatives 8a-10a of C-nitromethyl-1,2,3,4,5-cyclohexanepentols, respectively. On treatment with diazomethane in DMSO, the ketones 6 and 7 gave single spiro epoxides 11 and 12, the structures of which were confirmed by converting them into new C-(azidomethyl)cyclohexanepentols 16 and 17. The nitro compounds were hydrogenated in the presence of Raney nickel to give the amines isolated as the N-acetyl derivatives. Deprotection gave three new 1- and 3-C-aminomethyldeoxyinositols 15c-17c. The aminocyclitols obtained and their N-acetyl derivatives were assayed for inhibitory activity against examples of glycosidases.