methyl (3RS)-3-<(tert-butyldimethylsilyl)oxy>-6-(dimethoxyphosphinyl)-5-oxohexanoate | 144149-66-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: methyl (3RS)-3-<(tert-butyldimethylsilyl)oxy>-6-(dimethoxyphosphinyl)-5-oxohexanoate
• 英文别名: methyl 3-[(tert-butyldimethylsilyl)oxy]-6-(dimethoxyphosphoryl)-5-oxohexanoate；(R)-6-(Dimethoxyphosphinyl)-3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-5-oxo-hexanoic acid,methyl ester；methyl 3-[(tert-butyldimethylsilyl)oxy]-6-(dimethoxyphosphinyl)-5-oxohexanoate；methyl 3-[(t-butyldimethylsilyl)oxy]-6-(dimethoxyphosphinyl)-5-oxohexanoate；3-tert-butyldimethylsilanyloxy-6-dimethoxyphosphoryl-5-oxo-hexanoic methyl ester；methyl 3-[tert-butyl(dimethyl)silyl]oxy-6-dimethoxyphosphoryl-5-oxohexanoate
• CAS: 144149-66-6
• 化学式: C₁₅H₃₁O₇PSi
• 分子量: 382.466
• InChiKey: BDQQGXBWOLQHBU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.39
• 重原子数：
  24
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  88.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl (3RS)-3-<(tert-butyldimethylsilyl)oxy>-6-(dimethoxyphosphinyl)-5-oxohexanoate 在 氢氟酸 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 lithium chloride 作用下， 以 乙腈 为溶剂， 反应 11.0h， 生成 (E)-7-[2-(4-Fluoro-phenyl)-7-(4-isopropyl-benzyl)-4,5,6,7-tetrahydro-2H-indazol-3-yl]-3-hydroxy-5-oxo-hept-6-enoic acid methyl ester
  参考文献：
  名称：

  HMG-CoA reductase inhibitors: design, synthesis, and biological activity of tetrahydroindazole-substituted 3,5-dihydroxy-6-heptenoic acid sodium salts

  摘要：

  Compounds comprising a series of 7-[2-(4-fluorophenyl)-4,5,6,7-tetrahydro-2H-indazol-3-yl]-3,5-dihydroxy-6-heptenoic acid sodium salts (18) were synthesized and tested for their ability to inhibit HMG-CoA reductase in a partially purified enzyme preparation and cholesterol biosynthesis from acetate in cultured HEP-G2 cells. Changing the size of the saturated ring of the tetrahydroindazole nucleus did not improve potency, but incorporation of substituents at the 7-position resulted in up to 1700-fold improvement in inhibitory potency. Structure-activity studies revealed that the most potent compounds possess a substituted benzyl group at the 7-position, with a preference for steric bulk at the para position of the benzene ring. The most potent enzyme inhibitor (18t, IC50 = 3.0 nM) is approximately 3-fold more potent than lovastatin sodium salt (2). The most potent cholesterol biosynthesis inhibitor in HEP-G2 cells (18q, IC50 = 0.078 muM) is slightly less potent than 2 (sodium salt). Molecular modeling studies suggested that, when compared to the parent compound (18b) lacking the appropriate 7-substituent, 18t overlaps better with 2 and literature inhibitors 5 and 6 in a hydrophobic binding region adjacent to the enzyme active site.

  DOI：

  10.1021/jm00075a024
• 作为产物：
  描述：

  3-叔丁基二甲硅氧基戊二酸酐 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 9.0h， 生成 methyl (3RS)-3-<(tert-butyldimethylsilyl)oxy>-6-(dimethoxyphosphinyl)-5-oxohexanoate
  参考文献：
  名称：

  Chemoselective Synthesis of β-Ketophosphonates Using Lithiated α-(Trimethylsilyl)methylphosphonate

  摘要：

  A highly chemoselective synthesis of beta-ketophosphonates from pentafluorophenyl esters and lithiated methyl alpha-(trimethylsilyl)methylphosphonate has been developed. This mild lithiated phosphonate reagent allows the synthesis of functionalized beta-ketophosphonates in the presence of unactivated esters with high yields. This method has been compared with the standard lithiated methylphosphonate reagent.

  DOI：

  10.1021/acs.joc.5b00039

文献信息

• [EN] PROCESS AND INTERMEDIATES FOR THE SELECTIVE SYNTHESIS OF FLUVASTATIN<br/>[FR] PROCÉDÉ ET INTERMÉDIAIRES POUR LA SYNTHÈSE SÉLECTIVE DE LA FLUVASTATINE
  申请人：ZHEJIANG HISUN PHARMACEUTICAL

  公开号：WO2006021326A1

  公开（公告）日：2006-03-02

  The invention relates to process for the selective preparation of 3-hydroxy-6-dialkoxyphosphoryl-5-oxo-hexanoic acid esters, comprising a first step, in which a methylphosphonic acid dialkylester is treated with a base, and a second step, in which the product of the primary reaction is reacted with an optionally 3-protected 3-hydroxy-1,5-pentanoic diacid ester.

  这项发明涉及一种选择性制备3-羟基-6-二烷氧基磷酰基-5-氧代己酸酯的方法，包括第一步，在该步骤中，甲基膦酸二烷基酯与碱反应，以及第二步，在该步骤中，初级反应产物与可选的3-保护的3-羟基-1,5-戊二酸酯发生反应。
• Process for preparing a keto-phosphonate intermediate useful in
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US04804770A1

  公开（公告）日：1989-02-14

  A process is provided for preparing the keto-phosphonate ##STR1## in enantiomerically homogeneous form, by reacting the anhydride ##STR2## with S-.alpha.-methylbenzylamine to effect diastereoselective opening of the anhydride to give a mixture of amides ##STR3## separating the amides, for example, by frictional crystallization, and converting the desired amide IVA (which is obtained in high yield from the anhydride) to enantiomerically homogeneous ketophosphonate in high yield and on a large scale. The so-formed ketophosphonate is useful in the synthesis of compactin as well as 7-substituted-(3,5-dihydroxy)-hept-6-enoic and -heptanoic acid HMG-CoA reductase inhibitors.

  提供了一种制备酮磷酸酯##STR1##的过程，以对映异构体均一形式存在，通过将酐##STR2##与S-.alpha.-甲基苄胺反应，实现选择性开环酐生成一种酰胺混合物##STR3##，通过分离酰胺，例如通过摩擦结晶，将从酐中高产率获得的所需酰胺 IVA 转化为对映异构体均一的酮磷酸酯，产率高且规模大。这样形成的酮磷酸酯在紧凑素合成中以及7-取代-(3,5-二羟基)-庚-6-烯酸和-庚酸 HMG-CoA 还原酶抑制剂的合成中具有用途。
• Preparation of 3-oxy-5-oxo-6-heptenoic acid derivatives
  申请人：Ube Industries, Ltd.

  公开号：US05677455A1

  公开（公告）日：1997-10-14

  Methyl (3R,6E)-3-\x9b(tert-butyldimethylsilyl)oxy!-7-\x9b2\',6\'-diisopropyl-4\'-(4"-fluor ophenyl)-5'-(methoxymethyl)pyridin-3'-yl!-5-oxy-6-heptenoate or other 3-oxy-5-oxo-6-heptenoic acid derivative is prepared by the reaction of an aromatic aldehyde and an oxyglutaric acid derivative in an aliphatic alcohol containing a small amount of water in the presence of an alkali metal carbonate or hydrogen carbonate.

  (3R,6E)-3-叔丁基二甲基硅基氧基-7-2'，6'-二异丙基-4'-(4"-氟苯基)-5'-(甲氧甲基)吡啶-3'-基-5-氧基-6-庚烯酸酯或其他3-氧基-5-氧代-6-庚烯酸衍生物可通过芳香醛和羟基戊二酸衍生物在含少量水的脂肪醇中，在碱金属碳酸盐或氢碳酸盐存在下反应制备。
• Novel piperidine derivative
  申请人：Ban Hitoshi

  公开号：US20070078120A1

  公开（公告）日：2007-04-05

  The invention provides a compound of the following formula (1): wherein m, n, and p are independently an integer of 0-4, provided 3≦m+n≦8; X is nitrogen atom or a group of the formula: C—R 15 ; Y is a substituted or unsubstituted aromatic group, etc.; R 15 , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are hydrogen atom, a substituted or unsubstituted alkyl group, etc.; and Z is hydrogen atom, cyano group, etc., or a prodrug thereof, or a pharmaceutically acceptable salt thereof, which exhibits an action for enhancing LDL receptor expression, and is useful as a medicament for treating hyperlipidemia, atherosclerosis, etc.

  本发明提供了以下式(1)的化合物：其中m，n和p分别是0-4的整数，满足3≦m+n≦8；X是氮原子或式：C—R15的基团；Y是取代或未取代的芳香基团等；R15，R1，R2，R3，R4，R5，R6和R7是氢原子，取代或未取代的烷基等；Z是氢原子，氰基等，或其前药，或其药学上可接受的盐，具有增强LDL受体表达的作用，并且可用作治疗高脂血症，动脉粥样硬化等药物。
• EP1679069
  申请人：——

  公开号：——

  公开（公告）日：——