16-羟基-16-甲基-9-氧代-前列腺-10,13-二烯-1-酸甲酯 | 58682-86-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: 16-羟基-16-甲基-9-氧代-前列腺-10,13-二烯-1-酸甲酯
• 中文别名: 10,11 - 脱氢米索前列醇(非对映体的混合物)
• 英文名称: 16-Hydroxy-16-methyl-9-oxo-prosta-10,13-dien-1-oic acid methyl ester
• 英文别名: methyl 7-[(1R,2S)-2-[(E)-4-hydroxy-4-methyloct-1-enyl]-5-oxocyclopent-3-en-1-yl]heptanoate
• CAS: 58682-86-3
• 化学式: C₂₂H₃₆O₄
• 分子量: 364.525
• InChiKey: OCWJVIUDOHXKHI-PWNUKQCCSA-N

物化性质

• 溶解度：
  氯仿（微溶）、二氯甲烷（微溶）、甲醇（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  26
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  misoprostol 在 buffer solution 作用下， 以 甲醇 、 水 为溶剂， 生成 外消旋-11-脱氧-8(12)-去氢米索前列醇 、 、 16-羟基-16-甲基-9-氧代-前列腺-10,13-二烯-1-酸甲酯 、 Methyl 7-((1S,2R,3R)-3-hydroxy-2-((E)-4-hydroxy-4-methyloct-1-en-1-yl)-5-oxocyclopentyl)heptanoate
  参考文献：
  名称：

  关于前列腺素E1的β-羟基环戊酮类似物的脱水机理。

  摘要：

  β-羟基环戊酮，11,16-二羟基-16-甲基-9-氧代-13-反戊烯酸甲酯（一种前列腺素E1的类似物）的脱水通过未催化而进行酸催化（pH小于3）。路线（pH等于4且等于7），并具有碱催化作用（pH等于5-6且大于8）。pH等于1时，溶剂中的氘在60％反应时不会引入α到反应物的酮官能团中，但在pH等于5时发生了约30％的交换，在pH等于7时发生了50％的交换，而在pH等于80％时发生了交换。数据与9至9的数据是一致的。在该机理中，首先用酸，碱和水将底物催化催化烯醇化为1,3-烯二醇，然后通过酸，碱和水的催化使水松弛。第一步是在强酸溶液中测定速率

  DOI：

  10.1002/jps.2600730306

文献信息

• [EN] PROCESS FOR THE PREPARATION AND PURIFICATION OF MISOPROSTOL<br/>[FR] PROCÉDÉ DE PRÉPARATION ET DE PURIFICATION DE MISOPROSTOL
  申请人：CHINOIN PHARMACEUTICAL AND CHEMICAL WORKS PRIVATE CO LTD

  公开号：WO2019011668A1

  公开（公告）日：2019-01-17

  Preparation of the compounds of general formula I, among them misoprostol where R represents a straight‐ or branched‐chain C1-4 alkyl group by cuprate coupling of the vinyl cuprate of general formula II prepared by reacting the vinyl stannane of general formula III with copper halide CuX and alkyllithium R1Li wherein: R2 stands for H or an alcohol‐protecting group which may contain silicium atom, as for instance trimethylsilyl‐, triethylsilyl‐, tert.‐butyldimethylsilyl‐ group, or a cyclic or open‐chain alkyl group containing oxygen atom, as for instance tetrahydropyranyl‐, methoxymethyl‐ or ethoxymethyl‐ group; X means I, Br, CN, SCN, OSO2 CF3 group, R1 represents C1-6 alkyl group, n >2, if R2 is not hydrogen atom, n>3, if R2 is hydrogen atom, and the protected enone of the general formula IV 30 22 IV where R3 represents THP‐ or trialkylsilyl‐ group and the meaning of R is as defined above takes part in the cuprate reaction 5 in a manner that a.) the excess of the alkyllithium, which is applied as compared to the Cu(I) iodide in the case of R2 ≠ H in 2‐2.4 molar ratio, in the case of R2 = H in 3‐3.4 molar ratio, is decomposed before the coupling reaction of II and IV, b.) the protecting groups of the resulting compound of the general formula V 15 V where the meanings of R, R2 and R3 are as defined above are removed, the obtained compound of the general formula I is purified by chromatography.

  将一般公式I化合物的制备，其中包括米索前列醇，其中R代表直链或支链C1-4烷基基团，通过将一般公式III的乙烯基锡化合物与铜卤化物CuX和烷基锂R1Li反应制备得到一般公式II的乙烯基铜化合物，其中：R2代表H或可能含有硅原子的醇保护基团，例如三甲基硅基、三乙基硅基、叔丁基二甲基硅基或含氧原子的环状或链状烷基基团，例如四氢吡喃基、甲氧甲基或乙氧甲基基团；X代表I、Br、CN、SCN、OSO2 CF3基团，R1代表C1-6烷基基团，n>2，如果R2不是氢原子，则n>3，如果R2是氢原子，并且一般公式IV的受保护烯酮，其中R3代表THP或三烷基硅基团，R的含义如上所述，以一种方式参与铜酯反应，即a.)与Cu(I)碘化物相比，应用过量的烷基锂，在R2≠H的情况下为2-2.4摩尔比，在R2=H的情况下为3-3.4摩尔比，在II和IV的偶联反应之前分解，b.)去除一般公式V的所得化合物的保护基，其中R、R2和R3的含义如上所述，得到的一般公式I的化合物通过色谱纯化。
• Process for the preparation and purification of misoprostol
  申请人：CHINOIN PHARMACEUTICAL AND CHEMICAL WORKS PRIVATE CO. LTD.

  公开号：US10759734B2

  公开（公告）日：2020-09-01

  A process of preparing compounds of general formula I, by cuprate coupling of a vinyl cuprate of general formula II with a protected enone of general formula IV to produce a compound of general formula (V) removing the protecting groups of the compound of general formula (V) and purifying the compound of general formula (I) by chromatography; wherein the vinyl cuprate of formula (II) is prepared by reacting a vinyl stannane of formula III with copper halide CuX and alkyllithium R1Li and wherein an excess of the alkyllithium is decomposed before the said coupling reaction.

  一种通式 I 化合物的制备方法、 通过通式 II 的乙烯基铜酸盐的铜酸酯耦合 与通式 IV 的受保护烯酮 生成通式(V)的化合物 去除通式(V)化合物的保护基团，并通过色谱法纯化通式(I)化合物； 其中，式(II)的乙烯基铜酸盐是通过式Ⅲ的乙烯基锡烷与卤化铜CuX和烷基锂R1Li反应制备的 其中过量的烷基锂在上述偶联反应前被分解。
• COMPOSITIONS FOR PROLIFERATION OF CELLS AND RELATED METHODS
  申请人：The Hospital For Sick Children

  公开号：EP2598150A2

  公开（公告）日：2013-06-05
• PROCESS FOR THE PREPARATION AND PURIFICATION OF MISOPROSTOL
  申请人：CHINOIN PHARMACEUTICAL AND CHEMICAL WORKS PRIVATE CO. LTD.

  公开号：US20200165186A1

  公开（公告）日：2020-05-28

  Preparation of the compounds of general formula I, among them misoprostol where R represents a straight- or branched-chain C 1-4 alkyl group by cuprate coupling of the vinyl cuprate of general formula II prepared by reacting the vinyl stannane of general formula III with copper halide CuX and alkyllithium R 1 Li wherein: R 2 stands for H or an alcohol-protecting group which may contain silicium atom, as for instance trimethylsilyl-, triethylsilyl-, tert.-butyldimethylsilyl- group, or a cyclic or open-chain alkyl group containing oxygen atom, as for instance tetrahydropyranyl-, methoxymethyl- or ethoxymethyl- group; X means I, Br, CN, SCN, OSO 2 CF 3 group, R 1 represents C 1-6 alkyl group, n>2, if R 2 is not hydrogen atom, n>3, if R 2 is hydrogen atom, and the protected enone of the general formula IV 30 22 IV where R 3 represents THP- or trialkylsilyl-group and the meaning of R is as defined above takes part in the cuprate reaction 5 in a manner that a.) the excess of the alkyllithium, which is applied as compared to the Cu(I) iodide in the case of R 2 ≠H in 2-2.4 molar ratio, in the case of R 2 =H in 3-3.4 molar ratio, is decomposed before the coupling reaction of II and IV, b.) the protecting groups of the resulting compound of the general formula V 15 V where the meanings of R, R 2 and R 3 are as defined above are removed, the obtained compound of the general formula I is purified by chromatography.
• US8748177B2
  申请人：——

  公开号：US8748177B2

  公开（公告）日：2014-06-10