氨布洛芬合成工艺的优化

对氨布洛芬的合成工艺进行了优化。以甲苯为溶剂,布洛芬经酰氯化制得布洛芬酰氯;K2CO3作缚酸剂,布洛芬酰氯与乙醇胺完成酰胺化反应合成了氨布洛芬,收率94.4%,纯度99.09%。     

氟苯尼考琥珀酸单酯的合成工艺优化

以氟苯尼考和琥珀酸酐为原料,4-二甲氨基吡啶(DMAP)催化合成了氟苯尼考琥珀酸单酯。通过正交试验确定最佳反应条件为:氟苯尼考14 mmol,n(氟苯尼考)∶n(琥珀酸酐)=1.0∶1.5,w(DMAP)=4%,于60℃反应4 h,产率88.1%。在最佳反应条件下做放大实验,氟苯尼考3 kg,产率88.9%     

醋酸乌利司他关键中间体的合成工艺

3,20-二(亚乙二氧基)-17-α-羟基-19-去甲孕甾-5(10),9(11)-二烯为合成选择性孕酮受体调节剂醋酸乌利司他(Ulipristal Acetate)的关键中间体。以环-3-(1,2-亚乙基缩醛)-雌甾-5(10), 9(11)-二烯-3,17-二酮(UPA-O)为原料,经亲核取代、亲核加成、Mislow-Evans重排、醚键断裂、烯醇式互变、缩酮保护等反应,制备该关键中间体。对合成路线中反应条件进行工艺优化,总收率74.8%。     

二烯丙基双酚A合成工艺的优化

利用正交实验法研究了二烯丙基双酚A(DABPA)Claisen重排时进行工艺优化的条件,以及对DABPA纯度和粘度的影响,同时探讨的DABPA粘度的影响因素.实验结果表明,在220~230℃,反应2h,抽真空30min DABPA产品纯度最高,可达86.33%,粘度为1 300mPa·s.     

拉罗替尼的合成工艺优化

以(R)-2-(2,5-二氟苯基)吡咯烷和5-氯-3-硝基吡唑并［1,5-a］嘧啶为起始原料,经胺化,还原,再与氯甲酸苯酯酰化,最后与(S)-3-羟基吡咯烷反应成盐后得到拉罗替尼,总收率为73.34%。其结构经¹H NMR、IR及ESI-MS 确证,并探讨了中间体和目标化合物合成工艺的影响因素。      

HDAC6选择性抑制剂WT161的合成工艺优化

本文报道了一条新的合成HDAC6选择性抑制剂WT161的路线。以辛二酸单甲酯为起始原料,经缩合、取代、还原、脱水共四步反应得到HDAC6选择性抑制剂WT161,总收率64.8%,目标产物结构均经过~1HNMR、~(13)CNMR和HRMS等确证。优化后的工艺路线原料成本低、反应条件温和、反应后处理更简单、产物收率更高,比较适合较大规模制备。     

伊马替尼的合成及其中间体工艺优化

以3-乙酰基吡啶为起始原料,经环合、缩合、还原、酰胺化等六步反应制得抗肿瘤药物伊马替尼,并对其中间体N-(2-甲基-5-硝基苯基)-4-(3-吡啶基)嘧啶-2-胺的后处理工艺进行了优化,降低了成本和操作难度,有利于工业化。     

基底细胞癌新药Sonidegib的合成工艺优化

以2-氯-5-硝基吡啶为起始原料,经氢化、偶联和酰胺缩合反应合成Sonidegib,总收率71.4%,其结构经¹H NMR和MS（ESI）确证。     

阿糖胞苷的合成工艺研究

本文报道了一条新的阿糖胞苷合成路线。以氰乙酸乙酯、尿素、原甲酸三乙酯为原料,经缩合、环化、水解和脱羧合成胞嘧啶,其与四乙酰基核糖进行Silyl反应,后水解得到胞苷,胞苷在氯化亚砜、二甲基亚砜(DMSO)作用下生成环胞苷,环胞苷水解得到产物阿糖胞苷。总收率21.35%,产物结构经¹HNMR、¹³CNMR和ESI-MS确证,HPLC纯度检测为99.8%。     

GEN-617的合成工艺优化

以便宜易得的对氟苯甲腈(2)为起始原料经亲核取代、氧化、还原得到关键中间体(5),5与咪唑并[1,2-α]吡啶-7-羧酸(6)缩合以56.4％总收率制得GEN-617.该路线原料易得、反应条件温和、操作简单,具有良好的工业化前景.     

维布妥昔单抗关键中间体的合成工艺优化

本研究对维布妥昔单抗关键中间体(1)的合成工艺进行了改进与优化。以芴甲氧羰基-L-缬氨酸琥珀酰亚胺酯(2)为起始原料,先后经酯的氨解反应、酰胺化、Fmoc脱保护、酰胺化与酯交换反应制得目标产品1,总收率11.6%,纯度99.2%,产物结构经1H NMR, 13C NMR和HRMS表征。优化后的工艺路线具有反应条件温和、可操作性强、生产过程更安全的特点。在初步放大试验中,首步投料量达百克级别,并已完成三批工艺验证,适合于工业化生产。     

Design,Synthesis, and Biological Evaluation of HDAC Degraders with CRBN E3 Ligase Ligands

Histone deacetylases (HDACs) play important roles in cell growth, cell differentiation, cell apoptosis, and many other cellular processes. The inhibition of different classes of HDACs has been shown to be closely related to the therapy of cancers and other diseases. In this study, a series of novel CRBN-recruiting HDAC PROTACs were designed and synthesized by linking hydroxamic acid and benzamide with lenalidomide, pomalidomide, and CC-220 through linkers of different lengths and types. One of these PROTACs, denoted 21a, with a new benzyl alcohol linker, exhibited comparably excellent HDAC inhibition activity on different HDAC classes, acceptable degradative activity, and even better in vitro anti-proliferative activities on the MM.1S cell line compared with SAHA. Moreover, we report for the first time the benzyl alcohol linker, which could also offer the potential to be used to develop more types of potent PROTACs for targeting more proteins of interest (POI).     

Printed Circuit Board-Based Electrolyte Regulator for Laminar Microfluidics

The trench on a printed circuit board was reconstructed to fabricate a microfluidic framework that allows low-cost production for small quantities and integration with multifunctional elements. An on-chip electrolyte regulator was thus proposed on this platform to analyze diffusion properties in laminar flow. A numerical model was developed, highlighting the interplay between the electrolyte migration and hydrodynamic properties. Solutions with dissolved sodium chloride were simulated and experimentally tested for the regulation of electrical conductivity under the guidance of the normalized Nernst-Planck equation. The diffusion mechanism and the resulting concentration field were demonstrated in detail. This approach provides a satisfactory manufacturing method and a useful tool for integrated microfluidic systems.     

Parallel Optimization of Synthetic Pathways within the Network of Organic Chemistry

Finding a needle in a haystack: The number of possible synthetic pathways leading to the desired target of a synthesis can be astronomical (10(19) within five synthetic steps). Algorithms are described that navigate through the entire known chemical-synthetic knowledge to identify optimal synthetic pathways. Examples are provided to illustrate single-target optimization and parallel optimization of syntheses leading to multiple targets.     

甲苯作为环糊精包合作用的空间调节器的研究

以芘为模拟荧光探针 ,研究了甲苯对γ -环糊精 (γ -CD) -芘 (Py)包合体系的影响。发现Py -γ -CD -甲苯形成 1∶1∶1的包合物 ,并测出该包合物的包合常数。结果表明 :甲苯的加入 ,大大增强了γ -CD内腔与Py的结合力。     

新型绿色植物生长调节剂——芸苔素内酯的研究进展*

芸苔素内酯是一种新型绿色环保植物生长调节剂,具有促进植物生长、提高植物抗逆抗病能力、改善植物生长品质等多方面功能,被视为第六类植物生长激素。概述了芸苔素内酯的研究进展,介绍了芸苔素内酯在农业生产中的应用,为推动芸苔素内酯的广泛使用提供参考。