(4R,5R)-1,3-dibenzyl-5-(mercaptomethyl)imidazolidin-2-one-4-carboxylic acid | 112878-95-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (4R,5R)-1,3-dibenzyl-5-(mercaptomethyl)imidazolidin-2-one-4-carboxylic acid
• 英文别名: (4R,5R)-1,3-dibenzyl-5-mercaptomethyl-2-oxothiazolidine-4-carboxylic acid；(4R,5R)-1,3-dibenzyl-2-oxo-5-(mercaptomethyl)-imidazolidin-4-carboxylic acid；(4R,5R)-1,3-dibenzyl-2-oxo-5-(mercaptomethyl)imidazolidin-4-carboxylic acid；(4R,5R)-1,3-dibenzyl-2-oxo-5-mercaptomethylimidazolidine-4-carboxylic acid；(4R,5R)-1,3-dibenzyl-2-oxo-5-(sulfanylmethyl)imidazolidine-4-carboxylic acid
• CAS: 112878-95-2
• 化学式: C₁₉H₂₀N₂O₃S
• 分子量: 356.445
• InChiKey: HJZIBQKDKBSYQR-DLBZAZTESA-N

物化性质

• 熔点：
  159-160 °C
• 沸点：
  605.8±55.0 °C(Predicted)
• 密度：
  1.313±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  61.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4R,5R)-1,3-dibenzyl-5-(mercaptomethyl)imidazolidin-2-one-4-carboxylic acid 在 palladium dihydroxide 吡啶 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 氯仿 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 7.0h， 生成 5-[(3aR,6aS)-1,3-Dibenzyl-2-oxo-hexahydro-thieno[3,4-d]imidazol-(6E)-ylidene]-pentanoic acid ethyl ester
  参考文献：
  名称：

  2-Thiazolidinone: a novel thiol protective surrogate of complete atom efficiency, a practical synthesis of (+)-biotin

  摘要：

  2-Thiazolidinone derivatives were shown to be novel protective surrogates of a thiol group in L-cysteine derivatives. After elaboration at the C-4 substituent, the thiol group was completely liberated by simple heating in DMF whose atom efficiency is 100%. A practical synthesis of (+)-biotin was accomplished by the use of the strategy employing 4-functionalized 2-thiazolidinone derivatives as the intermediates, allowing a synthesis of (+)-biotin in 10 steps and in 31%, overall yield. Short steps, high yield, and ease of operation of the present approach Would permit the hitherto most efficient access to (+)-biotin. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2003.09.202
• 作为产物：
  描述：

  benzylamino-2-[(2R,4R)-3-phenoxycarbonyl-2-phenylthiazolidin-4-yl]acetonitrile 在 盐酸 、 双氧水 、 potassium carbonate 、 溶剂黄146 、 锌 作用下， 以 溶剂黄146 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.0h， 生成 (4R,5R)-1,3-dibenzyl-5-(mercaptomethyl)imidazolidin-2-one-4-carboxylic acid
  参考文献：
  名称：

  通过 Strecker 反应轻松合成 (+)-生物素的关键中间体

  摘要：

  (2R,4R)-2-phenyl-3-phenoxycarbonylthiazolidine-4-carbaldehyde (4b)（由 L-半胱氨酸容易制备）与苄胺和三甲基甲硅烷基氰化物的 Strecker 反应立体选择性地提供 α-氨基腈 5b（顺反, 2:1)。5b 的酰胺化和随后的环化得到双环化合物 6，它在用锌粉还原、水解和随后的环化后，提供硫内酯 2，它是 (+)-生物素 (1) 的关键中间体。

  DOI：

  10.1055/s-2003-42399

文献信息

• A Practical Synthesis of (+)-Biotin fromL-Cysteine
  作者：Masahiko Seki、Masanori Hatsuda、Yoshikazu Mori、Shin-ichi Yoshida、Shin-ichi Yamada、Toshiaki Shimizu

  DOI：10.1002/chem.200400733

  日期：2004.12.3

  which is readily derived from L-cysteine through cyclization and elaboration of the carboxy group, was subjected to the Strecker reaction, which, via sodium bisulfite adduct 16, afforded alpha-amino nitrile 5 with high diastereoselectivity (syn/anti=11:1) and in high yield. Amide 6, derived from 5, was converted to thiolactone 8, a key intermediate in the synthesis of (+)-biotin (1), by a novel S,N-carbonyl

  易于通过环化和羧基化衍生自L-半胱氨酸的α-氨基醛4经受Strecker反应，该反应通过亚硫酸氢钠加合物16得到具有高非对映选择性的α-氨基腈5（syn /反= 11：1），且收率很高。通过新的S，N-羰基迁移和环化反应，将5衍生的酰胺6转化为硫代内酯8，这是合成（+）-生物素（1）的关键中间体。在非均相Pd / C催化剂的存在下，8与具有酯基的锌试剂21的福山偶联反应使4-羧基丁基链的有效安装提供了9。化合物9进行了氢化，保护基团去除后可分10步提供1种，L-半胱氨酸的总收率为34％。
• An efficient and practical procedure for Strecker reaction: a highly diastereoselective synthesis of a key intermediate for (+)-biotin
  作者：Masahiko Seki、Masanori Hatsuda、Shin-ichi Yoshida

  DOI：10.1016/j.tetlet.2004.07.034

  日期：2004.8

  aqueous solution of 6 was treated with benzylamine followed by easy-handling NaCN to effect the Strecker reaction to afford α-amino nitrile 3 with high diastereoselectivity and in high yield (syn/anti = 11:1, 95% assay yield). Both the compounds syn-3 and anti-3 were converted to a key intermediate 4 for (+)-biotin through S,N-carbonyl migration in high yields.

  用亚硫酸氢钠水溶液处理相应的β-氨基醇5并通过Moffatt氧化制得的α-氨基醛2，可将其干净地转化为水溶性亚硫酸氢盐加合物6 [> 99％转化率，89％收率（两步） ）]。用苄胺处理6的水溶液，然后用易处理的NaCN进行Strecker反应，以高非对映选择性和高收率（合成/抗 = 11：1，测定收率95％）提供α-氨基腈3。化合物syn - 3和anti - 3都被转化为关键中间体。4为（+） -生物素通过小号，Ñ以高收率羰迁移。
• Intermediate for biotin and process for producing the same
  申请人：Seki Masahiko

  公开号：US20050038260A1

  公开（公告）日：2005-02-17

  The present invention is to provide a process for preparing a synthetic intermediate of biotin which is industrially advantageous, and discloses a process for preparing a compound represented by the formula (I): wherein R 1 and R 2 may be the same or different from each other, and each represents hydrogen atom, a benzyl group which may have a substituent(s) on the benzene ring, a benzhydryl group which may have a substituent(s) on the benzen ring, or a trityl group which may have a substituent(s) on the benzene ring, R 3 represents cyano group, carboxyl group, an alkoxycarbonyl group, an alkylthiocarbonyl group, or a carbamoyl group which may have a substituent, or a salt thereof which comprises subjecting a compound represented by the formula (II-a): wherein the symbols have the same meanings as defined above, or a salt thereof to ring transformation.

  本发明提供了一种制备生物素合成中间体的工业优势过程，并披露了一种制备由式(I)表示的化合物的过程：其中R1和R2可以相同也可以不同，分别代表氢原子、苯甲基，苯环上可能带有取代基的苯甲基，苯环上可能带有取代基的苯基甲基，或苯环上可能带有取代基的三苯甲基；R3代表氰基、羧基、烷氧基羰基、烷基硫酰基、或可能带有取代基的氨基甲酰基，或其盐；该过程包括将式(II-a)表示的化合物：其中符号具有上述定义的相同含义，或其盐进行环转化。
• Biotin intermediate and process for preparing the same
  申请人：Seki Masahiko

  公开号：US20080119655A1

  公开（公告）日：2008-05-22

  The present invention is to provide a process for preparing a synthetic intermediate of biotin which is industrially advantageous, and discloses a process for preparing a compound represented by the formula (I): 1 wherein R 1 and R 2 may be the same or different from each other, and each represents hydrogen atom, a benzyl group which may have a substituent(s) on the benzene ring, a benzhydryl group which may have a substituent(s) on the benzen ring, or a trityl group which may have a substituent(s) on the benzene ring, R 3 represents cyano group, carboxyl group, an alkoxycarbonyl group, an alkylthiocarbonyl group, or a carbamoyl group which may have a substituent, or a salt thereof which comprises subjecting a compound represented by the formula (II-a): 2 wherein the symbols have the same meanings as defined above, or a salt thereof to ring transformation.

  本发明提供了一种制备生物素合成中间体的工业优势过程，并揭示了一种制备由式(I)表示的化合物的过程：其中R1和R2可以相同也可以不同，分别表示氢原子，苯基（苯环上可能有取代基），苯基甲基（苯环上可能有取代基），或三苯甲基（苯环上可能有取代基）；R3表示氰基，羧基，烷氧基羰基，烷基硫氧基羰基或氨基甲酰基（可能带有取代基），或其盐，该过程包括将式(II-a)表示的化合物：其中符号具有上述定义的相同含义，或其盐进行环转化。
• Novel practical stereoselective synthesis of a bicyclic hydantoino-thiolactone as the key intermediate for production of (+)-biotin
  作者：Lei Shu、Zhi-Wei Yang、Ren-Xu Cao、Xiao-Xia Qiu、Feng Ni、Xiao-Xin Shi

  DOI：10.1039/d3ra04721k

  日期：——

  Bicyclic hydantoinothiolactone (1), as the key intermediate for production of (+)-biotin, has been efficiently and high-stereoselectively synthesized from the cheap starting material l-cystine via nine steps in 44% overall yield. In this new practical synthesis, there are two characteristic steps worthy of note. One step is TMSOTf-catalyzed efficient cyanation of (3S,7aR)-6-benzyl-5-oxo-3-phenyltetrahydro-1H

  双环乙内酰硫代内酯 (1) 作为生产 (+)-生物素的关键中间体，以廉价的起始原料 L-胱氨酸为原料，经过九步高效、高立体选择性合成，总产率为 44%。在这个新的实用合成中，有两个特征步骤值得注意。第一步是TMSOTf催化(3S,7aR)-6-苄基-5-氧代-3-苯基四氢-1H,3H-咪唑并[1,5-c]噻唑-7-乙酸酯的高效氰化，另一步是DBU 催化双环乙内酰硫内酯的反式异构体快速异构化为顺式异构体。