6-isothiocyanatohexan-1-ol | 194154-00-2

• 分子结构分类: 有机化合物 - 有机硫化合物 - 异硫氰酸盐
• 英文名称: 6-isothiocyanatohexan-1-ol
• 英文别名: 6-Hydroxyhexyl isothiocyanate
• CAS: 194154-00-2
• 化学式: C₇H₁₃NOS
• 分子量: 159.252
• InChiKey: BVRKUIBRWFSSSE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  10
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  64.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-isothiocyanatohexan-1-ol 在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 以27%的产率得到6-isothiocyanatohexanal
  参考文献：
  名称：

  异硫氰酸盐的一氧化氮的生产活性与其极性表面积相关，而不与其亲脂性相关

  摘要：

  对具有不同作用机理的新型抗炎药的需求不断增长。我们基于辛辣香料山葵（Wasabia japonica）中发现的6-（甲基亚磺酰基）己基异硫氰酸酯（6-MITC）合成了一系列异硫氰酸酯2b - h。注意到使用小鼠巨噬细胞样细胞系J774.1对肿瘤细胞体外生长的抑制活性和一氧化氮（NO）的产生。通过Hartree-Fock / 3-21G模型优化所有异硫氰酸酯，并计算log  P值和极性表面积（PSA）值。的甲基亚磺酰基的取代（CH 3 S（O）-R）在6- MITC与甲酰基（CHO-R），甲基硫（CH 2S–R）或甲基（CH 3 –R）基团会降低母体异硫氰酸酯的活性。用甲酰基取代会导致较低的亲脂性（log  P值），而用甲硫基或甲基取代会导致较低的PSA值。异硫氰酸酯的抑制活性显示出与其PSA值更好的相关性，而不是其分配系数（log  P）值。具有较高PSA值和一定程度log P值的异硫氰酸酯 可能具有强大的生物活性。

  DOI：

  10.1016/j.ejmech.2009.08.005
• 作为产物：
  描述：

  2-(6-isothiocyanatohexyloxy)-tetrahydro-2H-pyran 在 对甲苯磺酸 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以71%的产率得到6-isothiocyanatohexan-1-ol
  参考文献：
  名称：

  异硫氰酸盐的一氧化氮的生产活性与其极性表面积相关，而不与其亲脂性相关

  摘要：

  对具有不同作用机理的新型抗炎药的需求不断增长。我们基于辛辣香料山葵（Wasabia japonica）中发现的6-（甲基亚磺酰基）己基异硫氰酸酯（6-MITC）合成了一系列异硫氰酸酯2b - h。注意到使用小鼠巨噬细胞样细胞系J774.1对肿瘤细胞体外生长的抑制活性和一氧化氮（NO）的产生。通过Hartree-Fock / 3-21G模型优化所有异硫氰酸酯，并计算log  P值和极性表面积（PSA）值。的甲基亚磺酰基的取代（CH 3 S（O）-R）在6- MITC与甲酰基（CHO-R），甲基硫（CH 2S–R）或甲基（CH 3 –R）基团会降低母体异硫氰酸酯的活性。用甲酰基取代会导致较低的亲脂性（log  P值），而用甲硫基或甲基取代会导致较低的PSA值。异硫氰酸酯的抑制活性显示出与其PSA值更好的相关性，而不是其分配系数（log  P）值。具有较高PSA值和一定程度log P值的异硫氰酸酯 可能具有强大的生物活性。

  DOI：

  10.1016/j.ejmech.2009.08.005

文献信息

• Na₂S₂O₈-mediated efficient synthesis of isothiocyanates from primary amines in water
  作者：Zhicheng Fu、Wenhao Yuan、Ning Chen、Zhanhui Yang、Jiaxi Xu

  DOI：10.1039/c8gc02261e

  日期：——

  We have developed two green, practical, and efficient procedures, including a one-pot one, to synthesize isothiocyanates from amines and carbon disulfide via desulfurization with sodium persulfate. Water is used as the solvent. Basic conditions are necessary for good chemoselectivity for isothiocyanates. Structurally diverse linear and branched alkyl amines and aryl amines are readily converted to isothiocyanates

  我们已经开发了两种绿色，实用且有效的方法，包括一锅法，可通过胺和二硫化碳通过胺合成异硫氰酸酯。用过硫酸钠脱硫。使用水作为溶剂。为了使异硫氰酸酯具有良好的化学选择性，必须具备碱性条件。通过两种方法，结构令人满意的直链和支链烷基胺和芳基胺很容易以令人满意的产率转化为异硫氰酸酯。卤素，苄基CH键，甲硫基，硝基，酯，烯基，富电子或不足的（杂）芳基，乙炔基，甚至酚和醇羟基均被很好地耐受。在水中一锅法也可用于从手性胺制备手性异硫氰酸酯，以及用游离氨基修饰生物活性结构。在大规模制备中，开发了独立于柱色谱法的简单实用的纯化方法。
• Direct, Microwave-Assisted Synthesis of Isothiocyanates
  作者：Łukasz Janczewski、Anna Gajda、Tadeusz Gajda

  DOI：10.1002/ejoc.201900105

  日期：2019.4.16

  Application of microwave technique allowed to accomplish novel, general and “greener” one‐pot protocol for the synthesis of isothiocyanates from amines. Reactions are easily scalable and take place without racemization of chiral amines. Decomposition of the intermediate dithiocarbamates into isothiocyanates proceeds without any additional desulfurating agent under these conditions.

  微波技术的应用允许完成从胺类合成异硫氰酸酯的新颖，通用，“绿色”的一锅操作规程。反应易于扩展并且在不消旋手性胺的情况下进行。在这些条件下，中间体二硫代氨基甲酸酯可分解为异硫氰酸酯，而无需任何其他脱硫剂。
• Functional biopolymer modification reagents and uses thereof
  申请人：Schwartz A. David

  公开号：US20050203289A1

  公开（公告）日：2005-09-15

  Hydrazino, oxyamino and carbonyl-based reagents and methods for incorporation into oligonucleotides during their solid phase synthesis are provided. Modified oligonucleotides are provided that incorporate the reagents provided herien. Immobilized oligonucleotides and oligonucleotide conjugates that contain covalent hydrazone or oxime linkages are provided. Methods for preparation of surface bound oligonucleotides are provided. Methods for the preparation of oligonucleotide conjugates are also provided.

  提供了基于肼基、氧胺基和羰基试剂的方法，用于在固相合成寡核苷酸过程中将其合并。提供了修改的寡核苷酸，其中包含此处提供的试剂。提供了包含共价肼酮或肟键合的固定化寡核苷酸和寡核苷酸共轭物。提供了制备表面固定化寡核苷酸的方法。还提供了制备寡核苷酸共轭物的方法。
• Isothiocyanates (ITCs) 1-(Isothiocyanatomethyl)-4-phenylbenzene and 1-Isothiocyanato-3,5-bis(trifluoromethyl)benzene—Aldehyde Dehydrogenase (ALDH) Inhibitors, Decreases Cisplatin Tolerance and Migratory Ability of NSCLC
  作者：Jolanta Kryczka、Jakub Kryczka、Łukasz Janczewski、Anna Gajda、Andrzej Frączyk、Joanna Boncela、Beata Kolesińska、Ewa Brzeziańska-Lasota

  DOI：10.3390/ijms23158644

  日期：——

  One of the main treatment modalities for non-small-cell lung cancer (NSCLC) is cisplatin-based chemotherapy. However, the acquisition of cisplatin resistance remains a major problem. Existing chemotherapy regimens are often ineffective against cancer cells expressing aldehyde dehydrogenase (ALDH). As such, there is an urgent need for therapies targeting ALDH-positive cancer cells. The present study compares the anticancer properties of 36 structurally diverse isothiocyanates (ITCs) against NSCLC cells with the ALDH inhibitor disulfiram (DSF). Their potential affinity to ALDH isoforms and ABC proteins was assessed using AutoDockTools, allowing for selection of three compounds presenting the strongest affinity to all tested proteins. The selected ITCs had no impact on NSCLC cell viability (at tested concentrations), but significantly decreased the cisplatin tolerance of cisplatin-resistant variant of A549 (A549CisR) and advanced (stage 4) NSCLC cell line H1581. Furthermore, long-term supplementation with ITC 1-(isothiocyanatomethyl)-4-phenylbenzene reverses the EMT phenotype and migratory potential of A549CisR to the level presented by parental A549 cells, increasing E-Cadherin expression, followed by decreased expression of ABCC1 and ALDH3A1. Our data indicates that the ALDH inhibitors DSF and ITCs are potential adjuvants of cisplatin chemotherapy.

  非小细胞肺癌（NSCLC）的主要治疗模式之一是以顺铂为基础的化疗。然而，获得顺铂耐药性仍然是一个主要问题。现有的化疗方案通常对表达醛脱氢酶（ALDH）的癌细胞无效。因此，迫切需要针对ALDH阳性癌细胞的治疗方法。本研究比较了36种结构多样的异硫氰酸酯（ITC）与ALDH抑制剂二硫化物（DSF）对NSCLC细胞的抗癌性能。使用AutoDockTools评估它们与ALDH同工酶和ABC蛋白的潜在亲和力，以选择出三种对所有测试蛋白的亲和力最强的化合物。所选的ITC对NSCLC细胞的存活率没有影响（在测试浓度下），但显著降低了顺铂耐药变异株A549CisR和晚期（第四期）NSCLC细胞系H1581的顺铂耐受性。此外，长期补充ITC 1-异硫氰酸甲基-4-苯基苯烷可逆转A549CisR的EMT表型和迁移潜力，使其达到与母细胞A549相同的水平，增加E-Cadherin表达，随后降低ABCC1和ALDH3A1的表达。我们的数据表明，ALDH抑制剂DSF和ITC是顺铂化疗的潜在辅助治疗药物。
• Multiple binding modes of isothiocyanates that inhibit macrophage migration inhibitory factor
  作者：Emma S. Spencer、Edward J. Dale、Aimée L. Gommans、Malcolm T. Rutledge、Christine T. Vo、Yoshio Nakatani、Allan B. Gamble、Robin A.J. Smith、Sigurd M. Wilbanks、Mark B. Hampton、Joel D.A. Tyndall

  DOI：10.1016/j.ejmech.2015.02.012

  日期：2015.3

  Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that has roles in the innate immune response, and also contributes to inflammatory disease. While the biological properties of MIF are closely linked to protein protein interactions, MW also has tautomerase activity. Inhibition of this activity interferes with the interaction of MIF with protein partners e.g. the CD74 receptor, and tautomerase inhibitors show promise in disease models including multiple sclerosis and colitis. Isothiocyanates inhibit MIF tautomerase activity via covalent modification of the N-terminal proline. We systematically explored variants of benzyl and phenethyl isothiocyanates, to define determinants of inhibition. In particular, substitution with hydroxyl, chloro, fluoro and trifluoro moieties at the para and meta positions were evaluated. In assays on treated cells and recombinant protein, the IC50 varied from 250 nM to >100 mu M. X-ray crystal structures of selected complexes revealed that two binding modes are accessed by some compounds, perhaps owing to strain in short linkers between the isothiocyanate and aromatic ring. The variety of binding modes confirms the existence of two subsites for inhibitors and establishes a platform for the development of potent inhibitors of MIF that only need to target one of these subsites. (C) 2015 Elsevier Masson SAS. All rights reserved.