3-iodopropionaldehyde ethylene acetal | 58135-25-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氧戊环
• 英文名称: 3-iodopropionaldehyde ethylene acetal
• 英文别名: 2-(3-iodopropyl)-1,3-dioxolane；2-(3-iodopropyl)[1,3]dioxolane；ethylene ketal 4-iodobutanal；2-(3-iodo-propyl)-[1,3]dioxolane；2-<3-Iod-propyl>-1,3-dioxolan
• CAS: 58135-25-4
• 化学式: C₆H₁₁IO₂
• 分子量: 242.057
• InChiKey: SOWHPUBSACYGKJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  9
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-iodopropionaldehyde ethylene acetal 在 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 24.0h， 以90%的产率得到4-碘丁醛
  参考文献：
  名称：

  Polymer conjugates of the highly potent cytostatic drug 2-pyrrolinodoxorubicin

  摘要：

  This paper describes the synthesis and biological evaluation of a conjugate of the highly cytotoxic drug 2-pyrrolinodoxorubicin (p-DOX) with an N-(2-hydroxypropyl)methacrylamide copolymer (PHPMA) as a water-soluble biocompatible polymer carrier, utilizing the advantageous concept of polymer-drug conjugates. The conjugate of p-DOX with HPMA copolymer (PHPMA/p-DOX) was prepared by reacting the PHPMA/DOX conjugate, where the DOX was bound via a hydrazone bond, with 4-iodobutyraldehyde. The hydrazone bond between the polymer and drug is susceptible to pH-controlled hydrolysis, enabling prolonged stability in circulation and fast p-DOX release under conditions mimicking the intracellular environment. The in vitro cytostatic activity of free p-DOX was in accordance with literature, whereas its PHPMA conjugate exhibited a 1.3- to 5-fold lower cytotoxicity, depending on the cancer cell line, when compared to the free p-DOX. This is in qualitative agreement with the data obtained for DOX and its HPMA copolymer conjugates. On mice bearing T-cell EL4 lymphoma, no tumor suppression was observed from the free p-DOX at a subtoxic dose of 0.1 mg/kg, whereas the PHPMA/p-DOX conjugate significantly inhibited the initial tumor growth at approximately equitoxic doses of 0.4 and 0.8 mg p-DOX eq/kg. However, moderately elevated doses of the p-DOX equivalent in the conjugate caused toxic effects, making accurate dosage setting essential. (C) 2010 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ejps.2010.11.006
• 作为产物：
  描述：

  2-(3-溴丙基)-1,3-二氧戊环 在 lithium iodide 作用下， 以 四氢呋喃 为溶剂， 以68%的产率得到3-iodopropionaldehyde ethylene acetal
  参考文献：
  名称：

  Asymmetric synthesis and structural assignment of (−)-α-conhydrine

  摘要：

  The first asymmetric synthesis of the conium alkaloid (-)-alpha-conhydrine is reported. Starting from a protected glycol aldehyde hydrazone as chiral precusor, a short route based on our alpha-alkylation/1,2-addition methodology has been developed. After cleavage of the auxiliary and simultaneous deprotection, the concluding ring closure is accomplished under reductive amination conditions. The title compound is obtained in moderate overall yield and in excellent diastereo- and enantiomeric excess (d.e., e.e. >96%). Single-crystal X-ray crystallography as well as H-1 NMR NOE experiments confirm the expected relative and absolute (2R,7S)-configuration of the product. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(02)00066-6
• 作为试剂：
  描述：

  二异丙胺 、 、 正丁基锂 、 N-(2-hydroxy-1-methyl-2-phenylethyl)-N-methyl-alpha-aminoacetamide monohydrate 、 氯化锂 、 四氢呋喃 在 氮气 、 3-iodopropionaldehyde ethylene acetal 、 四氢呋喃 、 水 、 Tetrahydrofuran hexane 、 盐酸 、 二氯甲烷 作用下， 以 hexanes 为溶剂， 反应 28.0h， 以to afford [αS-[αR*(1S*,2S*)]]-α-amino-N-(2-hydroxy-1-methyl-2-phenylethyl)-N-methyl-1,3-dioxolane-2-pentanamide as an oil (60 g)的产率得到alpha-Amino-N-(2-hydroxy-1-methyl-2-phenylethyl)-N-methyl-1, 3-dioxolane-2-pentanamide
  参考文献：
  名称：

  Preparation of (S)-2-amino-6,6-dimethoxyhexanoic acid methyl ester via novel dioxolanes

  摘要：

  该公式中的甘氨酰胺与二氧兰反应，其中L是离去基团，例如碘、溴、烷基磺酰氧或芳基磺酰氧，得到公式的二氧兰。将公式III的二氧兰在水回流条件下处理，然后用二甲氧基乙醇与甲酸甲酯交换二氧兰缩醛，并引入甲酯基，得到(S)-2-氨基-6,6-二甲氧基己酸甲酯，该中间体是制备双重抑制剂[4S-[4&agr;(R*),7&agr;,10a&bgr;]]-八氢-4-[(2-巯基-1-氧代-3-苯基丙基)-氨基]-5-氧代-7H-吡啶[2,1-b][1,3]噻吩-7-羧酸的中间体。还公开了(S)-2-氨基-6,6-二甲氧基己酸甲酯的储存稳定盐。

  公开号：

  US06329542B1

文献信息

• Preparation of (S)-2-amino-6, 6-dimethoxyhexanoic acid methyl ester via
  申请人：Bristol-Myers Squibb Co.

  公开号：US06166227A1

  公开（公告）日：2000-12-26

  The glycinamide of the formula (I) ##STR1## is reacted with the dioxolane of the formula (II) ##STR2## wherein L is a leaving group such as iodo, bromo, alkylsulfonyloxy, or arylsulfonyloxy to give the dioxolane of the formula (III) ##STR3## Treatment of (III) gives the dioxolane pentanoic acid IV ##STR4## which can be converted to (S)-2-amino-6,6-dimethoxyhexanoic acid, methyl ester.

  将式(I)的甘氨酰胺与式(II)的二氧兰反应，其中L是离去基团，如碘、溴、烷基磺酰氧或芳基磺酰氧，得到式(III)的二氧兰。处理(III)得到二氧兰戊酸IV，可以转化为(S)-2-氨基-6,6-二甲氧基己酸甲酯。
• Preparation of (s)-2-amino-6,6-dimethoxyhexanoic acid methyl ester via novel dioxolanes
  申请人：Bristol-Myers Squibb Co.

  公开号：US06248882B1

  公开（公告）日：2001-06-19

  The glycinamide of the formula is reacted with the dioxolane of the formula wherein L is a leaving group such as iodo, bromo, alkylsulfonyloxy, or arylsulfonyloxy to give the dioxolane of the formula Treating the dioxolane of formula III under aqueous refluxing conditions followed by exchanging the dioxolane acetal with a dimethoxy acetal and introduction of the methyl ester gives (S)-2-amino-6,6-dimethoxyhexanoic acid, methyl ester which is an intermediate in the preparation of the dual inhibitor [4S-[4&agr;(R*),7&agr;, 10a&bgr;]]-)octahydro-4-[(2-mercapto-1-oxo-3-phenylpropy)-amino]-5-oxo-7H-pyrido[2,1-b][1,3]thiazepine-7-carboxylic acid. Also disclosed are storage stable salts of (S)-2-amino-6,6-dimethoxyhexanoic acid, methyl ester.

  该公式中的甘氨酰胺与二氧兰反应，其中L是离去基团，例如碘、溴、烷基磺酰氧或芳基磺酰氧，得到公式的二氧兰。在水回流条件下处理公式III的二氧兰，然后用二甲氧基乙醇交换二氧兰缩醛，并引入甲酯基，得到(S)-2-氨基-6,6-二甲氧基己酸甲酯，这是制备双重抑制剂[4S-[4&agr;(R*),7&agr;,10a&bgr;]]-)八氢-4-[(2-巯基-1-氧代-3-苯基丙基)-氨基]-5-氧代-7H-吡啶[2,1-b][1,3]噻吩-7-羧酸的中间体。此外，还披露了(S)-2-氨基-6,6-二甲氧基己酸甲酯的储存稳定盐。
• Asymmetric Total Synthesis of Twin Bufogargarizins A and B
  作者：Li-Ping Zhong、Rui Feng、Jing-Jing Wang、Chuang-Chuang Li

  DOI：10.1021/jacs.2c13494

  日期：2023.2.1

  The first and asymmetric total synthesis of bufogargarizins A and B, two unusual and highly oxygenated twin steroids with rearranged A/B rings, was achieved. The synthetically challenging [7–5–6–5] tetracyclic ring system of bufogargarizin A was efficiently constructed by the first intramolecular Ru-catalyzed [5 + 2] cycloaddition reaction of a vinyl ether cyclopropane-yne. Notably, the interesting

  bufogargarizins A 和 B 是两种不寻常且高度氧化的双类固醇，具有重排的 A/B 环，首次实现了不对称全合成。通过乙烯基醚环丙烷炔的第一个分子内 Ru 催化的 [5 + 2] 环加成反应，有效地构建了具有合成挑战性的 bufogargarizin A [7-5-6-5] 四环系统。值得注意的是，有趣的 [5-7-6-5] 蟾蜍加利津 B 四环骨架通过来自 [7-5-6-5] 四环框架的独特逆醛醇/跨环醛醇级联反应非对映选择性地重新组装。
• Asymmetric epoxidation of allylic alcohols employing 4,5-diphenyloxazole as a masked ester functionality
  作者：Lendon N. Pridgen、S.C. Shilcrat、I. Lantos

  DOI：10.1016/s0040-4039(01)81303-4

  日期：1984.1
• Thromboxane synthase inhibitors. Synthesis and pharmacological activity of (R)-, (S)-, and (.+-.)-2,2-dimethyl-6-[2-(1H-imidazol-1-yl)-1-[[(4-methoxyphenyl)methoxy]methyl]ethoxy]hexanoic acids
  作者：Paul W. Manley、David P. Tuffin、Nigel M. Allanson、Philip E. Buckle、Nagin Lad、Steve M. F. Lai、David O. Lunt、Roderick A. Porter、Patricia J. Wade

  DOI：10.1021/jm00393a022

  日期：1987.10

  A series of substituted omega-[2-(1H-imidazol-1-yl)ethoxy]alkanoic acid derivatives were synthesized and evaluated for their ability to inhibit thromboxane synthase both in vitro and in vivo. Compound 13 was identified as a potent and selective competitive inhibitor of human platelet thromboxane synthase having a Ki value of 9.6 X 10(-8) M. In collagen-treated human whole blood, 13 potentiated levels of 6-keto PGF1 alpha. Enantiospecific syntheses afforded the R and S enantiomers of 13, of which the S enantiomer 13b was the more potent. Compounds 13 and 13b were potent in vivo inhibitors of thromboxane synthase with good oral activity and duration of action.