(R)-4-(2,2-dimethyl-1,3-dioxolan-4-yl)butyric acid | 142560-61-0

• 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: (R)-4-(2,2-dimethyl-1,3-dioxolan-4-yl)butyric acid
• 英文别名: 4-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]butanoic acid
• CAS: 142560-61-0
• 化学式: C₉H₁₆O₄
• 分子量: 188.224
• InChiKey: VSMBNPYJOPORJT-SSDOTTSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-4-(2,2-dimethyl-1,3-dioxolan-4-yl)butyric acid 在 钯 重铬酸吡啶 、 Amberlyst 15 、 4 A molecular sieve 、 potassium tert-butylate 、 氢气 作用下， 以 四氢呋喃 为溶剂， 反应 9.0h， 生成 戊基糖三乙酸酯
  参考文献：
  名称：

  5-formyl-δ—valerolactone : A useful synthon for the chiral synthesis of the vespa orientalis pheromone and the mosquito oviposition attractant pheromone

  摘要：

  A synthetic scheme starting from the reaction between the lithiated N-allyl-N-methyl-(bisdimethylamino)phosphoramide anion and the triflate derivative of (R)-(-)- or (S)-(+)-2,3-O-isopropylideneglycerol is described to prepare the key chiral synthon (R)-5- or (S)-5-formyl-delta-valerolactone that leads to the title compounds.

  DOI：

  10.1016/s0040-4039(00)74412-1
• 作为产物：
  描述：

  [(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl trifluoromethanesulfonate 在 sodium hydroxide 、 正丁基锂 、 硫酸 、 草酸 、 silver nitrate 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 3.5h， 生成 (R)-4-(2,2-dimethyl-1,3-dioxolan-4-yl)butyric acid
  参考文献：
  名称：

  5-formyl-δ—valerolactone : A useful synthon for the chiral synthesis of the vespa orientalis pheromone and the mosquito oviposition attractant pheromone

  摘要：

  A synthetic scheme starting from the reaction between the lithiated N-allyl-N-methyl-(bisdimethylamino)phosphoramide anion and the triflate derivative of (R)-(-)- or (S)-(+)-2,3-O-isopropylideneglycerol is described to prepare the key chiral synthon (R)-5- or (S)-5-formyl-delta-valerolactone that leads to the title compounds.

  DOI：

  10.1016/s0040-4039(00)74412-1

文献信息

• A New DNA Gyrase Inhibitor Subclass of the Cyclothialidine Family Based on a Bicyclic Dilactam−Lactone Scaffold. Synthesis and Antibacterial Properties
  作者：Peter Angehrn、Erwin Goetschi、Hans Gmuender、Paul Hebeisen、Michael Hennig、Bernd Kuhn、Thomas Luebbers、Peter Reindl、Fabienne Ricklin、Anne Schmitt-Hoffmann

  DOI：10.1021/jm1014023

  日期：2011.4.14

  The DNA gyrase inhibitor cyclothialidine had been shown to be a valuable lead structure for the discovery of new antibacterial classes able to overcome bacterial resistance to clinically used drugs. Bicyclic lactone derivatives containing in their 12−14-membered ring a thioamide functionality were reported previously to exhibit potent antibacterial activity against Gram-positive bacteria. Moderate

  对于发现能够克服细菌对临床使用药物的耐药性的新型抗菌剂而言，DNA回旋酶抑制剂环噻啶已被证明是有价值的先导结构。先前已报道在其12-14元环中含有硫酰胺官能团的双环内酯衍生物对革兰氏阳性细菌表现出有效的抗菌活性。然而，仅对于带有亲水性取代基的衍生物证明了中等的体内功效，发现该衍生物对药物动力学具有有利的影响，并减少了代谢降解，特别是葡萄糖醛酸化。将一个额外的酰胺单元掺入环噻啶类似物的14元单内酰胺-内酯支架中，提供了一种新的固有的极性更高的DNA促旋酶抑制剂“双内酰胺”亚类。
• Synthesis of the polyether fragment A/B-ring system of tetronomycin.
  作者：Kozo HORI、Keiichi NOMURA、Naotsuka HIKAGE、Eiichi YOSHII

  DOI：10.1248/cpb.38.1781

  日期：——

  The polyether fragment 18 of tetronomycin (1) that contains the tetrahydrofuryl and tetrahydropyranyl groups has been synthesized via a Lewis acid-catalyzed coupling of a 2-methoxytetrahydrofuran 16 with a 2-(1-trimethylsilyl-2-propen-1-yl)tetrahydropyran 15.

  通过路易斯酸催化2-甲氧基四氢呋喃16与2-(1-三甲基硅烷基-2-丙烯-1-基)四氢吡喃15的偶联反应，合成了含有四氢呋喃基和四氢吡喃基的聚醚片段18。
• Mono or bicyclic DNA gyrase inhibitors
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0675122A2

  公开（公告）日：1995-10-04

  The present invention relates to mono- or bicyclic compounds of the general formula wherein X1is -S- or -SO-; R1is hydrogen, halogen or lower alkyl, optionally substituted by halogen ; R2is hydrogen, hydroxy, amino, lower alkylamino, di-lower alkylamino, optionally substituted lower alkoxy or a group -OP; OPis an easily hydrolyzable group; R3is hydrogen, hydroxy, lower alkyl, halogen or a group -OP; R4is halogen, hydroxy or a group -OP; R5is hydrogen, cyano, optionally substituted esterified carboxy or optionally substituted amidated (thio)carboxy, optionally substituted alkyl, optionally substituted alkenyl or optionally substituted heterocyclyl; R6is -NR7-A, -N=B or optionally substituted heterocyclyl, in which R7 is hydrogen or lower alkyl, A is optionally substituted iminoyl, optionally substituted (thio)acyl, optionally substituted esterified carboxy, optionally substituted amidated (thio)carboxy or optionally substituted heterocyclyl and B is optionally substituted alkylidene; R0is cyano, optionally substituted esterified carboxy or optionally substituted heterocyclyl, or wherein R0 and R6taken together represent a group         -CO-O-Q-X2-N(R7)-, wherein R7is as above, and X2is (thio)carbonyl or heterocyclyl; Qis -CH(R8)- or -CH(R8)-W-; R8is hydrogen or optionally substituted lower alkyl, and Wis optionally substituted mono-, di-, tri-, tetra- or pentamethylene, provided that when W is monomethylene X2 is other than (thio)carbonyl, and pharmaceutically acceptable salts of the mono- or bicyclic compounds of formula I carrying an acidic and/or basic substituent. These compounds of formula I as well as their pharmaceutically acceptable salts inhibit DNA gyrase activity in bacteria and possess antibiotic, especially antibacterial activity against microorganisms and can be used in the control or prevention of infectious diseases.

  本发明涉及通式如下的单环或双环化合物 其中 X1是-S-或-SO-； R1是氢、卤素或低级烷基，任选被卤素取代； R2 是氢、羟基、氨基、低级烷基氨基、二低级烷基氨基、任选被取代的低级烷氧基或基团 -OP； OP 是易水解基团； R3 是氢、羟基、低级烷基、卤素或基团 -OP R4 是卤素、羟基或基团 -OP R5是氢、氰基、任选取代的酯化羧基或任选取代的酰胺化（硫代）羧基、任选取代的烷基、任选取代的烯基或任选取代的杂环基； R6是-NR7-A、-N=B或任选取代的杂环基，其中R7是氢或低级烷基，A是任选取代的亚氨基酰基、任选取代的（硫代）酰基、任选取代的酯化羧基、任选取代的酰胺化（硫代）羧基或任选取代的杂环基，B是任选取代的亚烷基； R0 是氰基、任选取代的酯化羧基或任选取代的杂环基，或其中 R0 和 R6 合在一起代表一个基团 -CO-O-Q-X2-N(R7)-、 其中 R7 如上，以及 X2 是（硫代）羰基或杂环基； Q是-CH(R8)-或-CH(R8)-W-； R8 是氢或任选取代的低级烷基，以及 Wis 任选取代的一亚甲基、二亚甲基、三亚甲基、四亚甲基或五亚甲基，但当 W 为一亚甲基时，X2 不是（硫代）羰基、 和 带有酸性和/或碱性取代基的式 I 单环或双环化合物的药学上可接受的盐。 这些式 I 化合物及其药学上可接受的盐类可抑制细菌中 DNA 回旋酶的活性，并具有抗生素活性，特别是对微生物的抗菌活性，可用于控制或预防传染性疾病。
• Total synthesis of tetronomycin
  作者：Kozo Hori、Naotsuka Hikage、Atsushi Inagaki、Shuho Mori、Keiichi Nomura、Eiichi Yoshii

  DOI：10.1021/jo00036a026

  日期：1992.5

  The first total synthesis of (+)-tetronomycin (1), a novel tetronic acid ionophore antibiotic, has been achieved through the synthesis and assemblage of the four cyclic segments 4, 5, 7, and 8. Construction of the C5-C-13 cyclohexyl portion 5 involves as the key step either a Beckmann fragmentation of the bicyclic ketone oxime 45 or an L-Selectride-mediated reductive annulation of the nona-2,7-dienoate 53. The C-14-C28 polyether fragment 6 was constructed by a BF3-catalyzed coupling reaction of the C-14-C22 allylsilane 7 and the C23-C28 tetrahydrofuran 8 which were derived, respectively, from L-ascorbic acid or (R)-3-hydroxyisobutyrate and L-rhamnal. The union of 5 and 6 by an aldol condensation, followed by photoisomerization of the derived diastereomeric alpha,beta-unsaturated esters, provided (Z)-61, which was converted to the aldehyde 63. Subsequent acylation of the tetronate 4 with 63 via an aldol reaction-oxidation sequence afforded the protected tetronomycin 64. Final deprotection provided synthetic tetronomycin, which was characterized as its sodium salt.
• New Antibacterial Agents Derived from the DNA Gyrase Inhibitor Cyclothialidine
  作者：Peter Angehrn、Stefan Buchmann、Christoph Funk、Erwin Goetschi、Hans Gmuender、Paul Hebeisen、Dirk Kostrewa、Helmut Link、Thomas Luebbers、Raffaello Masciadri、Joergen Nielsen、Peter Reindl、Fabienne Ricklin、Anne Schmitt-Hoffmann、Frank-Peter Theil

  DOI：10.1021/jm0310232

  日期：2004.3.1

  Cyclothialidine (1, Ro 09-1437) is a potent DNA gyrase inhibitor that was isolated from Streptomyces filipinensis NR0484 and is a member of a new family of natural products. It acts by competitively inhibiting the ATPase activity exerted by the B subunit of DNA gyrase but barely exhibits any growth inhibitory activity against intact bacterial cells, presumably due to insufficient permeation of the cytoplasmic membrane. To explore the antibacterial potential of 1, we developed a flexible synthetic route allowing for the systematic modification of its structure. From a first set of analogues, structure-activity relationships (SAR) were established for different substitution patterns, and the 14-hydroxylated, bicyclic core (X) of 1 seemed to be the structural prerequisite for DNA gyrase inhibitory activity. The variation of the lactone ring size, however, revealed that activity can be found among 11- to 16-membered lactones, and even seco-analogues were shown to maintain some enzyme inhibitory properties, thereby reducing the minimal structural requirements to a rather simple, hydroxylated benzyl sulfide (XI). On the basis of these "minimal structures" a modification program afforded a number of inhibitors that showed in vitro activity against Gram-positive bacteria. The best activities were displayed by 14-membered lactones, and representatives of this subclass exhibit excellent and broad in vitro antibacterial activity against Gram-positive pathogens, including Staphylococcus aureus, Streptococcus pyogenes, and Enterococcus faecalis, and overcome resistance against clinically used drugs. By improving the pharmacokinetic properties of the most active compounds (94, 97), in particular by lowering their lipophilic properties, we were able to identify congeners of cyclothialidine (1) that showed efficacy in vivo.