Lebedinskiy Konstantin, Jindřich Jindřich
Department of Organic Chemistry, Faculty of Science, Charles University, Hlavova 8, CZ-128 43 Prague, Czech Republic.
ACS Omega. 2023 Jul 27;8(31):28268-28276. doi: 10.1021/acsomega.3c01950. eCollection 2023 Aug 8.
A series of 6-monohalo (Cl, Br, and I) β-cyclodextrin derivatives with various types of methylations were synthesized via a diazotization/nucleophilic displacement reaction from the corresponding methylated cyclodextrin amines. All four starting compounds (6-amino-6-deoxy derivatives of native β-CD, per-6--methyl-, per-2,3--methyl-, and per-2,3,6--methyl-β-CD) were found to have different reactivities under the same reaction conditions. Unsubstituted and fully per-O-methylated cyclodextrin amines undergo fast transformation, giving lower yields of the monohalogenated product. The selectively methylated cyclodextrin amines react remarkably slower and provide almost complete conversion into the desired monohalogenated compound. A pure product was, in several cases, successfully isolated with simple purification techniques (extraction and precipitation), allowing large-scale preparations. This new method opens the way for preparing poorly investigated monofunctionalized selectively methylated cyclodextrins.
通过重氮化/亲核取代反应，从相应的甲基化环糊精胺合成了一系列具有不同甲基化类型的6-单卤代（Cl、Br和I）β-环糊精衍生物。发现所有四种起始化合物（天然β-环糊精的6-氨基-6-脱氧衍生物、全-6-甲基-、全-2,3-甲基-和全-2,3,6-甲基-β-环糊精）在相同反应条件下具有不同的反应活性。未取代的和全-O-甲基化的环糊精胺发生快速转化，单卤代产物的产率较低。选择性甲基化的环糊精胺反应明显较慢，几乎完全转化为所需的单卤代化合物。在几种情况下，通过简单的纯化技术（萃取和沉淀）成功分离出纯产物，从而实现大规模制备。这种新方法为制备研究较少的单官能化选择性甲基化环糊精开辟了道路。
