(3aR,5R,6R,6aR)-2,2-dimethyl-5-(phenylmethoxymethyl)spiro[5,6a-dihydro-3aH-furo[2,3-d][1,3]dioxole-6,5'-oxolane]-2'-one | 188682-04-4

• 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: (3aR,5R,6R,6aR)-2,2-dimethyl-5-(phenylmethoxymethyl)spiro[5,6a-dihydro-3aH-furo[2,3-d][1,3]dioxole-6,5'-oxolane]-2'-one
• CAS: 188682-04-4
• 化学式: C₁₈H₂₂O₆
• 分子量: 334.369
• InChiKey: WAEMKESKLNNUKS-NOVWEMISSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  63.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (3aR,5R,6R,6aR)-2,2-dimethyl-5-(phenylmethoxymethyl)spiro[5,6a-dihydro-3aH-furo[2,3-d][1,3]dioxole-6,5'-oxolane]-2'-one 在 palladium on activated charcoal 咪唑 、 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 sodium periodate 、 偶氮二异丁腈 、 Dowex H¹⁺ resin 、 氢气 、 三正丁基氢锡 、 溶剂黄146 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 甲苯 为溶剂， 反应 51.0h， 生成 5-O-tert-butyldimethylsilyl-4-C-(2-(4-methoxyphenoxy)ethyl)-2,3-dideoxy-D-glycero-pentono-1,4-lactone
  参考文献：
  名称：

  Conformationally constrained diacylglycerol (DAG) analogs: 4-C-hydroxyethyl-5-O-acyl-2,3-dideoxy-D-glyceropentono-1,4-lactone analogs as protein kinase C (PKC) ligands

  摘要：

  The (R)-DAG-lactones (5 and 7E/Z) are conformationally constrained diacylglycerol (DAG) analogs with high potency as protein kinase C (PKC) ligands. Here, we have prepared and characterized their one-carbon lengthened analogs (6 and 8E/Z). The target compounds were synthesized from 1,2-O-isopropylidene D-xylose through a key intermediate, 4-C-hydroxyethyl-2,3-dideoxy-D-glyceropentono-1,4-lactone (13); they were evaluated as competitive ligands to displace bound [H-3]phorbol 12,13-dibutyrate (PDBU) from a recombinant single isozyme (PKC-alpha). The binding affinities of the synthesized compounds were K-i = 2.623 muM for 6, K-i = 1.080 muM for 8Z and K-i = 0.92 muM for 8E, which were ca. 27, 90, and 70 times less potent than the corresponding parent compounds (5, 7Z and 7E). Molecular modeling indicated that the reduced binding affinity of the representative 3-alkylidene lactone 8Z, as compared to 7Z, may be explained by its poor fit in the sn-1 binding mode as well as by its entropic loss due to the relatively flexible hydroxyethyl group. (C) 2003 Elsevier SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2003.10.006
• 作为产物：
  描述：

  (3aR,5R,6R,6aR)-5-Benzyloxymethyl-2,2-dimethyl-6-prop-2-ynyl-tetrahydro-furo[2,3-d][1,3]dioxol-6-ol 在 (cyclooctadienyl)(cyclopentadienyl)ruthenium chloride N-羟基丁二酰亚胺 、 三(2-呋喃基)膦 、 四丁基溴化铵 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以55%的产率得到(3aR,5R,6R,6aR)-2,2-dimethyl-5-(phenylmethoxymethyl)spiro[5,6a-dihydro-3aH-furo[2,3-d][1,3]dioxole-6,5'-oxolane]-2'-one
  参考文献：
  名称：

  Ruthenium-Catalyzed Cycloisomerization−Oxidation of Homopropargyl Alcohols. A New Access to γ-Butyrolactones

  摘要：

  Vinylidenemetal species, which readily form from terminal alkynes under mild conditions, have rarely been utilized as reactive intermediates in a catalytic cycle. The conversion of homopropargyl alcohols via such intermediates to metal-complexed oxacarbenes led to the development of an "oxidant" compatible with a ruthenium complex capable of performing the cycloisomerization, that would convert them to lactones. None of the oxidants known to stoichiometrically convert isolated metallooxacarbenes to esters are effective. The unconventional "oxidants", N-hydroxyimides, proved to be capable of effecting the desired transformation, with N-hydroxysuccinimide being the "oxidant" of choice. The procedure of choice employs cyclopentadienyl (1,4-cyclooctadiene) ruthenium chloride and trifuryl phosphine as the precatalyst in the presence of tetra-n-butylammonium bromide or hexafluorophosphate with N-hydroxysuccinimide as the oxidant in DMF-water at 95 degrees. In this way, a wide diversity of homopropargyl alcohols were converted to gamma-butyrolactones with excellent chemoselectivity. Lactones synthesized include an intermediate toward a platelet aggregation inhibitor, a fruit flavor principle, an inhibitor of binding of phorbol esters to PKC-alpha, a tobacco constituent, a wood constituent (quercus lactone), an aldosterone antagonist (spironolactone) precursor, and an acetogenin known for pesticidal and antitumor activities (muricatacin).

  DOI：

  10.1021/ja992013m

文献信息

• Ruthenium-Catalyzed Cycloisomerization−Oxidation of Homopropargyl Alcohols. A New Access to γ-Butyrolactones
  作者：Barry M. Trost、Young H. Rhee

  DOI：10.1021/ja992013m

  日期：1999.12.1

  Vinylidenemetal species, which readily form from terminal alkynes under mild conditions, have rarely been utilized as reactive intermediates in a catalytic cycle. The conversion of homopropargyl alcohols via such intermediates to metal-complexed oxacarbenes led to the development of an "oxidant" compatible with a ruthenium complex capable of performing the cycloisomerization, that would convert them to lactones. None of the oxidants known to stoichiometrically convert isolated metallooxacarbenes to esters are effective. The unconventional "oxidants", N-hydroxyimides, proved to be capable of effecting the desired transformation, with N-hydroxysuccinimide being the "oxidant" of choice. The procedure of choice employs cyclopentadienyl (1,4-cyclooctadiene) ruthenium chloride and trifuryl phosphine as the precatalyst in the presence of tetra-n-butylammonium bromide or hexafluorophosphate with N-hydroxysuccinimide as the oxidant in DMF-water at 95 degrees. In this way, a wide diversity of homopropargyl alcohols were converted to gamma-butyrolactones with excellent chemoselectivity. Lactones synthesized include an intermediate toward a platelet aggregation inhibitor, a fruit flavor principle, an inhibitor of binding of phorbol esters to PKC-alpha, a tobacco constituent, a wood constituent (quercus lactone), an aldosterone antagonist (spironolactone) precursor, and an acetogenin known for pesticidal and antitumor activities (muricatacin).
• Conformationally constrained diacylglycerol (DAG) analogs: 4-C-hydroxyethyl-5-O-acyl-2,3-dideoxy-D-glyceropentono-1,4-lactone analogs as protein kinase C (PKC) ligands
  作者：Jeewoo Lee、Su Yeon Kim、Ji-Hye Kang、Geza Acs、Peter Acs、Peter M Blumberg、Victor E Marquez

  DOI：10.1016/j.ejmech.2003.10.006

  日期：2004.1

  The (R)-DAG-lactones (5 and 7E/Z) are conformationally constrained diacylglycerol (DAG) analogs with high potency as protein kinase C (PKC) ligands. Here, we have prepared and characterized their one-carbon lengthened analogs (6 and 8E/Z). The target compounds were synthesized from 1,2-O-isopropylidene D-xylose through a key intermediate, 4-C-hydroxyethyl-2,3-dideoxy-D-glyceropentono-1,4-lactone (13); they were evaluated as competitive ligands to displace bound [H-3]phorbol 12,13-dibutyrate (PDBU) from a recombinant single isozyme (PKC-alpha). The binding affinities of the synthesized compounds were K-i = 2.623 muM for 6, K-i = 1.080 muM for 8Z and K-i = 0.92 muM for 8E, which were ca. 27, 90, and 70 times less potent than the corresponding parent compounds (5, 7Z and 7E). Molecular modeling indicated that the reduced binding affinity of the representative 3-alkylidene lactone 8Z, as compared to 7Z, may be explained by its poor fit in the sn-1 binding mode as well as by its entropic loss due to the relatively flexible hydroxyethyl group. (C) 2003 Elsevier SAS. All rights reserved.