7-Hydroxy-5-heptynoic Acid | 41300-59-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 7-Hydroxy-5-heptynoic Acid
• 英文别名: 7-hydroxyhept-5-ynoic acid；7-Hydroxy-5-heptinsaeure
• CAS: 41300-59-8
• 化学式: C₇H₁₀O₃
• mdl: MFCD19228385
• 分子量: 142.155
• InChiKey: YVZAOBOYHMHYKV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  10
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.571
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-Hydroxy-5-heptynoic Acid 在 nickel diacetate 吡啶 、 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 氢气 、 乙二胺 作用下， 以 乙醚 、 乙醇 、 二氯甲烷 为溶剂， 反应 9.0h， 生成 methyl 7-(tert-butyldiphenylsilyloxy)hept-5(Z)-enoate
  参考文献：
  名称：

  Analysis of oxidized glycerophosphocholine lipids using electrospray ionization mass spectrometry and microderivatization techniques

  摘要：

  Oxidized low-density lipoprotein (LDL) is thought to play an important role in atherogenesis and cardiovascular disease in humans. Oxidized LDL is a complex mixture of many oxidized species, including numerous oxidized glycerophospholipids. Electrospray ionization and tandem mass spectrometry as well as microchemical derivatization of high-performance liquid chromatographically purified fractions derived from oxidized LDL were investigated as means to determine the structure of individual components present in oxidized LDL. One major oxidized phosphocholine lipid had an [M + H](+) ion at m/z 650. Derivatization to the trimethylsilyl ether and methoxime caused shifts in mass which, along with negative ion collision-induced dissociation mass spectra, were consistent with the presence of three species, 1-palmitoyl-2-(9-oxononanoyl)glycerophosphocholine and two isomeric 1-octadecanoyl-2-(hydroxyheptenoyl)glycerophosphocholines. These species were chemically synthesized. Trimethylsilylation of free hydroxyl groups increased the mass of the phospholipid acyl chains containing hydroxyl groups by 72 u. Conversion of carbonyl groups to the methoxylamine derivative increased the mass by 29 u. Ozonolysis of those products which contained double bonds proved to be a facile technique to determine the position and number of double bonds present. The use of these techniques was illustrated in the structural characterization of one major component (m/z 650, positive ions) in oxidized LDL as 1-octadecanoyl-2-(7-hydroxy-hepta-5-enoyl)glycerophosphocholine. A possible mechanism for the formation of this unique chain-shortened glycerophospholipid is proposed. Copyright (C) 2000 John Wiley & Sons, Ltd.

  DOI：

  10.1002/(sici)1096-9888(200002)35:2<224::aid-jms933>3.0.co;2-g
• 作为产物：
  描述：

  2-(7'-hydroxyhept-2'-ynyloxy)tetrahydro-2H-pyran 在 重铬酸吡啶 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 7-Hydroxy-5-heptynoic Acid
  参考文献：
  名称：

  Haynes, Richard K.; Lambert, Dale E.; Parafiniuk, Krystyna A., Australian Journal of Chemistry, 1987, vol. 40, # 2, p. 273 - 280

  摘要：

  DOI：

文献信息

• Benzannulation of Triynes to Generate Functionalized Arenes by Spontaneous Incorporation of Nucleophiles
  作者：Rajdip Karmakar、Sang Young Yun、Jiajia Chen、Yuanzhi Xia、Daesung Lee

  DOI：10.1002/anie.201412468

  日期：2015.5.26

  The thermal reaction of ester‐tethered 1,3,8‐triynes provides novel benzannulation products with concomitant incorporation of a nucleophile. Evidence suggests that this reaction proceeds via an allene‐enyne intermediate generated by an Alder‐ene reaction in the first step. Depending on the substituent of the alkyne moiety on the allene‐enyne intermediate, the subsequent transformation can take one

  酯束缚的1,3,8-三炔的热反应提供了新的苯并环氧基化产物，并伴随有亲核试剂的结合。有证据表明，该反应是通过第一步中的Alder-ene反应生成的Allene-Enyne中间体进行的。根据丙二烯-烯炔中间体上炔基部分的取代基，后续的转化可采用两种不同的途径之一，每种途径可导致不连续的芳构化产物。硅烷取代的1,3,8-三炔的苯并环形成芳烃产品，并在新形成的苯核上掺入了亲核试剂，而芳基取代基导致亲核试剂捕获在与芳基取代基相连的苄基碳原子上。
• Discovery of an 8-Aza-5-thiaProstaglandin E1 Analog as a Highly Selective EP4 Receptor Agonist
  作者：Tohru Kambe、Toru Maruyama、Atsushi Naganawa、Masaki Asada、Akiteru Seki、Takayuki Maruyama、Hisao Nakai、Masaaki Toda

  DOI：10.1248/cpb.59.1494

  日期：——

  For the purpose of discovering an orally available EP4 subtype-selective agonist, a series of 8-aza prostaglandin E1 (PGE1) analogs were synthesized and evaluated for their affinity for PGE2 receptor subtypes. Additionally, the structure–activity relationships of these compounds were studied. Among the tested compounds, the 8-aza PGE1 analog 6 and 8-aza-5-thiaPGE1 analog 12 had highly potent EP4 receptor affinity, good functional activity, and excellent subtype-selectivity. Furthermore, these analogs demonstrated good stability in human liver microsomes. As a result, we concluded that these two series of 8-aza PGE1 analogs could be promising chemical leads for an orally available EP4 subtype-selective agonist.

  为了发现一种口服可用的EP4亚型选择性激动剂，合成并评估了一系列8-氮原子前列腺素E1（PGE1）类似物对PGE2受体亚型的亲和力。此外，还研究了这些化合物的结构-活性关系。在测试的化合物中，8-氮PGE1类似物6和8-氮-5-硫PGE1类似物12对EP4受体具有高效的亲和力、良好的功能活性和优异的亚型选择性。此外，这些类似物在人体肝微粒体中表现出良好的稳定性。因此，我们得出结论，这两系列的8-氮PGE1类似物可能是口服可用的EP4亚型选择性激动剂的有前景的化学先导物。
• Derivatives of prostanoic acid
  申请人：Ayerst McKenna & Harrison Ltd.

  公开号：US04054741A1

  公开（公告）日：1977-10-18

  Process for preparing prostanoic acid derivatives, in particular derivatives of 9,15-dioxygenated prostanoic acid and prost-13-enoic acid, related additionally unsaturated derivatives, homologs thereof and intermediates therefor, in which a lower alkyl ester of 2-(.omega.-carboxy-Y)cyclopent-2-en-1-one in which Y is CH.sub.2 --(a)--(CH.sub.2).sub.m wherein (a) is CH.sub.2 CH.sub.2, CH.dbd.CH or C.tbd.C and m is an integer from 2 - 4 is treated with nitromethane to yield 2-(.omega.-carboxy-Y)-3-nitromethyl-cyclopentan-1-one and the latter compound or its corresponding 1-hydroxy analog are converted to the corresponding aldehyde, 2-(.omega.-carboxy-Y)cyclopentan-1-on-3-al or 1-hydroxy-2-(.omega.-carboxy-Y)cyclopentan-3-al, respectively. Treatment of the aldehyde with the ylid prepared from the appropriate Wittig reagent, preferably a dimethyl 2-oxoalkylphosphonate of the formula (AlkO).sub.2 P(O)CH.sub.2 CO(CH.sub.2).sub.n CH.sub.3 in which n is an integer of from 1-6 and Alk is an alkyl containing from 1 - 3 carbon atoms yields the corresponding derivatives of 2-(.omega.-carboxy-Y)-3-(3-oxoalk-1-enyl)cyclopentan-1-one or -1-o1 in which the oxygen functions may be selectively protected and transformed by conventional means, and in which the unsaturated bonds may be reduced to a single bond. The prostanoic acid derivatives possess prostaglandin like biological activities. Methods for their use are also disclosed.

  制备前列腺酸衍生物的过程，特别是9,15-双氧代前列腺酸和前列腺-13-烯酸衍生物的过程，还包括相关的不饱和衍生物、同系物及其中间体。其中，将2-(ω-羧基-Y)环戊-2-烯-1-酮的低碳酸酯处理为亚硝甲烷，得到2-(ω-羧基-Y)-3-硝基甲基环戊-1-酮，然后将该化合物或其相应的1-羟基类似物转化为相应的醛，2-(ω-羧基-Y)环戊-1-酮-3-醛或1-羟基-2-(ω-羧基-Y)环戊-3-醛。将醛与由适当的威蒂格试剂制备的叶立得到的叶立体处理，最好是公式（AlkO）2P(O) CO(CH2)nCH3的二甲基2-氧代烷基膦酸酯，其中n是1-6的整数，Alk是含有1-3个碳原子的烷基，产生对应的2-(ω-羧基-Y)-3-(3-氧代烷-1-烯基)环戊-1-酮或-1-醇，在这些化合物中，氧功能基可能通过常规手段选择性地保护和转化，不饱和键可能被还原为单键。前列腺酸衍生物具有类似前列腺素的生物活性。同时还公开了它们的使用方法。
• Prostaglandin intermediates
  申请人：Ayerst McKenna and Harrison Ltd.

  公开号：US04006136A1

  公开（公告）日：1977-02-01

  A process for preparing 11-deoxyprostaglandin E.sub.1, E.sub.2 and E.sub.3 and analogs thereof is realized by treating an appropriate di(lower)alkyl 3-(optionally substituted)-2-formylcyclopropane-1,1-dicarboxylate with an ylid prepared from a Wittig reagent of formula (AlkO).sub.2 PCCH.sub.2 CO-(c)-CH.sub.3 in which Alk is an alkyl containing one to three carbon atoms and (c) is either (CH.sub.2).sub.q wherein q is an integer from 1 to 6 or cis CH.sub.2 CH=CH(CH.sub.2).sub.r wherein r is an integer from 0 to 3 to obtain the corresponding compound of formula: ##STR1## in which R.sup.2 is hydrogen, lower alkyl or CH.sub.2 OR.sup.3 wherein R.sup.3 is lower alkanoyl, R.sup.4 is lower alkyl and (c) is as defined herein. The latter compound is reduced with an alkali metal borehydride to yield the corresponding alcohol derivative. Condensation of this alcohol derivative or preferably its corresponding tetrahydropyran-2-yl ether derivative with a triester of formula CH(COOR.sup.6).sub.2 -(a)-(CH.sub.2)pCOOR in which R and R.sup.6 are lower alkyl, (a) is CH.sub.2 CH.sub.2, cis CH=CH or CaC and p is an integer from 2 to 4, gives the corresponding cyclopentanonetriester of formula ##STR2## in which (a), (c), p, R, R.sup.4 and R.sup.6 are as defined herein, R.sup.5 is hydrogen or tetrahydropyran-2-yl, respectively, and R.sup.7 is hydrogen or lower alkyl; the lactonized form of the cyclopentanone-triester being obtained from said alcohol derivative in which R.sup.2 is CH.sub.2 OR.sup.3 wherein R.sup.3 is lower alkanoyl. In the instance when R.sup.5 is tetrahydropyran-2-yl the cyclopentanonetriester is treated with an acid to give the corresponding compound in which R.sup.5 is hydrogen. The instant compound is then treated with a base under aqueous conditions, followed by optional esterification and acylation to give the desired 11-deoxy-prostaglandin derivatives of the formula ##STR3## in which (a), (c) and p, are as defined herein, (b) is trans CH=CH, R is hydrogen or lower alkyl, R.sup.1 is hydrogen or lower alkanoyl and R.sup.2 is hydrogen, lower alkyl or CH.sub.2 OR.sup.3 wherein R.sup.3 is hydrogen or lower alkanoyl. The derivatives possess prostaglandin-like biological activity and methods for their use are given.

  该过程是通过将适当的二(低)烷基3-(可选择取代)-2-甲醛环丙烷-1,1-二羧酸酯与由Wittig试剂制备的具有化学式(AlkO).sub.2PCCH.sub.2CO-(c)-CH.sub.3的偏磷酸酯反应来制备11-去氧前列腺素E.sub.1、E.sub.2和E.sub.3及其类似物。其中，Alk是含有一到三个碳原子的烷基，(c)可以是(CH.sub.2).sub.q，其中q是从1到6的整数，或者是顺式CH.sub.2CH=CH(CH.sub.2).sub.r，其中r是从0到3的整数，从而得到相应的化合物，其化学式为： 在这个化合物中，R.sup.2是氢、低烷基或CH.sub.2OR.sup.3，其中R.sup.3是低烷酰基，R.sup.4是低烷基，(c)如本文所定义。后一种化合物经碱金属硼氢化物还原得到相应的醇衍生物。将这种醇衍生物或更好地是其相应的四氢吡喃-2-基醚衍生物与具有化学式CH(COOR.sup.6).sub.2-(a)-(CH.sub.2)pCOOR的三酯缩合，其中R和R.sup.6是低烷基，(a)是CH.sub.2CH.sub.2、顺式CH=CH或CaC，p是从2到4的整数，得到相应的环戊酮三酯，其化学式为： 其中(a)、(c)、p、R、R.sup.4和R.sup.6如本文所定义，R.sup.5是氢或四氢吡喃-2-基，R.sup.7是氢或低烷基；环戊酮三酯的内酯形式可从上述R.sup.2为CH.sub.2OR.sup.3的醇衍生物中得到，其中R.sup.3是低烷酰基。当R.sup.5为四氢吡喃-2-基时，环戊酮三酯经酸处理得到R.sup.5为氢的相应化合物。然后，将该化合物在水性条件下处理碱，随后进行可选择的酯化和酰化，得到所需的11-去氧前列腺素衍生物，其化学式为： 其中(a)、(c)和p如本文所定义，(b)为顺式CH=CH，R是氢或低烷基，R.sup.1是氢或低烷酰基，R.sup.2是氢、低烷基或CH.sub.2OR.sup.3，其中R.sup.3是氢或低烷酰基。这些衍生物具有类似前列腺素的生物活性，并提供了它们的使用方法。
• 11 Hydroxy methyl 11-deoxyprostaglandin E.sub.1
  申请人：Ayerst, McKenna and Harrison Limited

  公开号：US04161608A1

  公开（公告）日：1979-07-17

  A process for preparing 11-deoxyprostaglandin E.sub.1, E.sub.2 and E.sub.3 and analogs thereof is realized by treating an appropriate di(lower)alkyl 3-(optionally substituted)-2-formylcyclopropane-1,1-dicarboxylate with an ylid prepared from a Wittig reagent of formula (AlkO).sub.2 POCH.sub.2 CO--(c)-CH.sub.3 in which Alk is an alkyl containing one to three carbon atoms and (c) is either (CH.sub.2).sub.q wherein q is an integer from 1 to 6 or cis CH.sub.2 CH.dbd.CH(CH.sub.2).sub.r wherein r is an integer from 0 to 3 to obtain the corresponding compound of formula: ##STR1## in which R.sup.2 is hydrogen, lower alkyl or CH.sub.2 OR.sup.3 wherein R.sup.3 is lower alkanoyl, R.sup.4 is lower alkyl and (c) is as defined herein. The latter compound is reduced with an alkali metal borohydride to yield the corresponding alcohol derivative. Condensation of this alcohol derivative or preferably its corresponding tetrahydropyran-2-yl ether derivative with a triester of formula CH(COOR.sup.6).sub.2 --(a)-(CH.sub.2)pCOOR in which R and R.sup.6 are lower alkyl, (a) is CH.sub.2 CH.sub.2, cis CH.dbd.CH or C.tbd.C and p is an integer from 2 to 4, gives the corresponding cyclopentanonetriester of formula ##STR2## in which (a), (c), p, R, R.sup.4 and R.sup.6 are as defined herein, R.sup.5 is hydrogen or tetrahydropyran-2-yl, respectively, and R.sup.7 is hydrogen or lower alkyl; the lactonized form of the cyclopentanonetriester being obtained from said alcohol derivative in which R.sup.2 is CH.sub.2 OR.sup.3 wherein R.sup.3 is lower alkanoyl. In the instance when R.sup.5 is tetrahydropyran-2-yl the cyclopentanonetriester is treated with an acid to give the corresponding compound in which R.sup.5 is hydrogen. The instant compound is then treated with a base under aqueous conditions, followed by optional esterification and acylation to give the desired 11-deoxy-prostaglandin derivatives of formula ##STR3## in which (a), (c) and p, are as defined herein, (b) is trans CH.dbd.CH, R is hydrogen or lower alkyl, R.sup.1 is hydrogen or lower alkanoyl and R.sup.2 is hydrogen, lower alkyl or CH.sub.2 OR.sup.3 wherein R.sup.3 is hydrogen or lower alkanoyl. The derivatives possess prostaglandin-like biological activity and methods for their use are given.

  一种制备11-去氧前列腺素E.sub.1，E.sub.2和E.sub.3及其类似物的方法，通过将适当的二（较低）烷基3-（可选取取代基）-2-甲酰基环丙烷-1,1-二羧酸酯与由公式（AlkO）.sub.2 POCH.sub.2 CO-制备的Wittig试剂的ylid处理，其中Alk是含有1至3个碳原子的烷基，（c）是（CH.sub.2）.sub.q，其中q是1至6的整数，或者是顺式CH.sub.2 CH=CH（CH.sub.2）.sub.r，其中r是0至3的整数，以得到相应的化合物的公式：##STR1## 其中R.sup.2是氢，较低的烷基或CH.sub.2 OR.sup.3，其中R.sup.3是较低的烷酰基，R.sup.4是较低的烷基，（c）如上所定义。后一种化合物用碱金属硼氢化物还原，得到相应的醇衍生物。将此醇衍生物或者更好的是其相应的四氢吡喃-2-基醚衍生物与公式CH（COOR.sup.6）.sub.2 --（a）-（CH.sub.2）pCOOR的三酯缩合，其中R和R.sup.6是较低的烷基，（a）是CH.sub.2 CH.sub.2，顺式CH=CH或C.tbd.C，p是2至4的整数，得到相应的环戊烷三酯的公式：##STR2## 其中（a），（c），p，R，R.sup.4和R.sup.6如上所定义，R.sup.5分别为氢或四氢吡喃-2-基，R.sup.7为氢或较低的烷基；从所述醇衍生物中得到环戊烷三酯的内酯形式，其中R.sup.2为CH.sub.2 OR.sup.3，其中R.sup.3为较低的烷酰基。当R.sup.5为四氢吡喃-2-基时，用酸处理环戊烷三酯，得到相应的化合物，其中R.sup.5为氢。然后在水性条件下将瞬时化合物处理为碱，随后进行可选的酯化和酰化，得到所需的公式：##STR3## 其中（a），（c）和p如上所定义，（b）为顺式CH=CH，R为氢或较低的烷基，R.sup.1为氢或较低的烷酰基，R.sup.2为氢，较低的烷基或CH.sub.2 OR.sup.3，其中R.sup.3为氢或较低的烷酰基。这些衍生物具有类似前列腺素的生物活性，并提供了其使用方法。