AVX-002

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: AVX-002
• 英文别名: (all-Z)-1,1,1-Trifluoro-4-thiadocosa-7,10,13,16,19-pentaen-2-one；1,1,1-Trifluoro-3-[[(3Z,6Z,9Z,12Z,15Z)-octadeca-3,6,9,12,15-pentenyl]thio]-2-propanone；1,1,1-trifluoro-3-[(3Z,6Z,9Z,12Z,15Z)-octadeca-3,6,9,12,15-pentaenyl]sulfanylpropan-2-one
• 化学式: C₂₁H₂₉F₃OS
• 分子量: 386.522
• InChiKey: MBGFSSHDEMMNDM-JLNKQSITSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  26
• 可旋转键数：
  14
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  42.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (3Z,6Z,9Z,12Z,15Z)-octadeca-3,6,9,12,15-pentaen-1-ol 在 lithium aluminium tetrahydride 、 偶氮二甲酸二异丙酯 、 碳酸氢钠 、 三苯基膦 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 为溶剂， 反应 3.0h， 生成 AVX-002
  参考文献：
  名称：

  Syntheses of some polyunsaturated trifluoromethyl ketones as potential phospholipase A2 inhibitors

  摘要：

  从（全-Z）-5,8,11,14,17-二十碳五烯酸[（全-Z）-5,8,11,14,17-二十碳五烯酸，EPA]和（全-Z）-4,7,10,13,16,19-二十二碳六烯酸（DHA）出发，已经合成了几种含有硫或氧原子在β位的三氟甲基酮，这些化合物被认为是细胞质磷脂酶A2的潜在抑制剂。作为这项工作的一部分，EPA和DHA分别被氧化降解为（全-Z）-3,6,9,12-十五碳四烯醛和（全-Z）-3,6,9,12,15-十八碳五烯醛，总产率均为75%。

  DOI：

  10.1039/b001944p

文献信息

• [EN] PROCESS FOR THE PREPARATION OF A POLYUNSATURATED KETONE COMPOUND<br/>[FR] PROCÉDÉ DE PRÉPARATION D'UN COMPOSÉ CÉTONE POLYINSATURÉ
  申请人：AVEXXIN AS

  公开号：WO2016116634A1

  公开（公告）日：2016-07-28

  A process for the preparation of a polyunsaturated thiol comprising: (1) reacting a polyunsaturated alcohol in the presence of a compound of formula R2-SO2Hal wherein R2 is a C1-20 hydrocarbyl group, such an C1-10 alkyl group, to form a polyunsaturated sulphonyl ester; (2) converting the polyunsaturated sulphonyl ester to a polyunsaturated thioester by reacting with an anion of formula -SC(=O)R4 wherein R4 is a C1-20 hydrocarbyl group; (3) converting the polyunsaturated thioester to form a polyunsaturated thiol optionally in the presence of an antioxidant, e.g. using a metal carbonate. (4) reacting said polyunsaturated thiol with a compound (LG)R3COX wherein X is an electron withdrawing group and R3 is an alkylene group carrying a leaving group (LG), such as LG-CH2- forming (I) where X is an electron withdrawing group and LG is a leaving group; optionally in the presence of an antioxidant, so as to form a polyunsaturated ketone compound.

  制备多不饱和硫醇的方法包括：（1）在式R2-SO2Hal的化合物存在下，将多不饱和醇与R2为C1-20烃基的化合物（如C1-10烷基）反应，形成多不饱和磺酰酯；（2）通过与式为-SC(=O)R4的阴离子反应，将多不饱和磺酰酯转化为多不饱和硫酯；（3）在抗氧化剂的存在下，将多不饱和硫酯转化为多不饱和硫醇，例如使用金属碳酸盐；（4）将所述多不饱和硫醇与化合物(LG)R3COX反应，其中X是一个电子吸引基团，R3是携带一个离去基团（LG）的烷基链，如LG-CH2-，形成(I)，其中X是一个电子吸引基团，LG是一个离去基团；在抗氧化剂的存在下，形成多不饱和酮化合物。
• PROCESS FOR THE PREPARATION OF A POLYUNSATURATED KETONE COMPOUND
  申请人：AVEXXIN AS

  公开号：US20160159737A1

  公开（公告）日：2016-06-09

  The invention relates to the manufacture of certain polyunsaturated compounds employing a particular application of the Mitsonobu reaction in the presence of at least one anti-oxidant. We have found a method of making a pharmaceutically-acceptable polyunsaturated ester or thioester compound directly, which can ultimately be converted to the advantageous ketone compounds, in which unwanted oxidation and cis/trans isomerization are substantially reduced or eliminated using particular Mitsonobu chemistry.

  本发明涉及利用Mitsonobu反应的特定应用来制造某些多不饱和化合物，其中至少存在一种抗氧化剂。我们发现了一种直接制造药用多不饱和酯或硫酯化合物的方法，最终可以转化为有利的酮化合物，其中使用特定的Mitsonobu化学方法，可以大大减少或消除不必要的氧化和顺反异构化。
• Process for the preparation of a polyunsaturated ketone compound
  申请人：Avexxin AS

  公开号：US10093618B2

  公开（公告）日：2018-10-09

  The invention relates to the manufacture of certain polyunsaturated compounds employing a particular application of the Mitsonobu reaction in the presence of at least one anti-oxidant. We have found a method of making a pharmaceutically-acceptable polyunsaturated ester or thioester compound directly, which can ultimately be converted to the advantageous ketone compounds, in which unwanted oxidation and cis/trans isomerization are substantially reduced or eliminated using particular Mitsonobu chemistry.

  本发明涉及在至少一种抗氧化剂存在的情况下，采用特定的 Mitsonobu 反应制造某些多不饱和化合物。我们发现了一种直接制造药学上可接受的多不饱和酯或硫酯化合物的方法，这种化合物最终可转化为有利的酮化合物，在这种方法中，利用特殊的 Mitsonobu 化学反应可大大减少或消除不需要的氧化和顺式/反式异构化。
• USE OF POLYUNSATURATED KETONES FOR THE TREATMENT OF PSORIASIS
  申请人：Johansen Berit

  公开号：US20100152293A1

  公开（公告）日：2010-06-17

  Psoriasis is a common, chronic, inflammatory skin disorder. This invention provides the use of a compound of formula (I) R—CO—X) (Wherein R is a C 16-24 unsaturated hydrocarbon group optionally interrupted by α, β, γ, or δ to the carbonyl group by a heteroatom or group of heteroatoms selected from S, O, N, SO, SO 2 said hydrocarbon group comprising at least 5 non-conjugated double bonds; and X is an electron withdrawing group) in the manufacture of a medicament for the treatment of psoriasis.
• US8524776B2
  申请人：——

  公开号：US8524776B2

  公开（公告）日：2013-09-03