53784-84-2Relevant articles and documents
Mechanistic Understanding of a Robust and Scalable Synthesis of Per(6-deoxy-6-halo)cyclodextrins, Versatile Intermediates for Cyclodextrin Modification
Zultanski, Susan L.,Kuhl, Nadine,Zhong, Wendy,Cohen, Ryan D.,Reibarkh, Mikhail,Jurica, Jon,Kim, Jungchul,Weisel, Lauren,Ekkati, Anil R.,Klapars, Artis,Gauthier, Donald R.,McCabe Dunn, Jamie M.
supporting information, p. 597 - 607 (2020/10/12)
Cyclodextrin (CD) perfunctionalization reactions are challenging to study because they proceed through a number of regioisomeric intermediates, thus warranting creative approaches to understanding the reaction mechanism. Particularly useful perfunctionalization targets are per(6-deoxy-6-halo)cyclodextrins. Their standard synthesis entails selective SN2 halogenation at their primary alcohols using a Vilsmeier reagent, but this requires a strongly basic quench to unmask the Vilsmeier-capped secondary alcohols. Herein we present an alternative and simple acidic hydrolytic quench that utilizes existing HX in the end-of-reaction solution and requires only the addition of water. We performed a detailed mechanistic investigation of the new quench, and a central feature was the use of proton sponge to develop an 1H NMR titration method for HX in organic solvent. This method was used to both quantify and remove HX in the prequenched reaction solution. The HX-free prequenched solution enabled us to (1) identify sensitive intermediates during the quench, (2) quantify all of the reaction byproducts, and (3) determine that HX is critical for hydrolysis. We then studied the halogenation reaction, wherein the new acidic quench facilitated high-throughput experimentation, using mass spectrometry as well as Design of Experiments with automated reaction profiling. Through this, we were able to establish robustness and understand the complex effects of Vilsmeier equivalents and temperature on the reaction outcome.
PROCESS FOR MAKING SUGAMMADEX
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Page/Page column 11; 12; 13, (2019/01/16)
The invention deals with a novel process for making intermediates of the pharmaceutically useful product Sugammadex of formula (1).
PROCESSES FOR THE PREPARATION OF SUGAMMADEX
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Page/Page column 23; 24, (2019/12/28)
The present invention provides processes for the preparation of sugammadex: (I) In one aspect, there is provided a process for the preparation of sugammadex from 8-per-deoxy-8-bromo-γ-cyclodextrin and 3-mercaptopropionic acid. In another aspect, there is provided an alternative process for the preparation of sugammadex from 8-per-deoxy-8-bromo-γ-cyclodextrin and disodium 3-mercaptopropionate. In another aspect, there is provided a process for the preparation of 8-per-deoxy-8-bromo-γ-cyclodextrin, which may be used in the production of sugammadex. In one such aspect, there is provided a process for the preparation of 8-per-deoxy-8-bromo-γ-cyclodextrin from γ-cyclodextrin and a brominating agent. In another such aspect, there is provided a process for the preparation of 8-per-deoxy-8-bromo-γ-cyclodextrin comprising, inter alia, reacting γ-cyclodextrin with an electrophilic brominating agent, a deoxygenating agent, and an acid in the presence of an organic solvent.
