22839-16-3Relevant articles and documents
Solvent-freeN-Boc deprotection byex situgeneration of hydrogen chloride gas
De Borggraeve, Wim M.,Gilles, Philippe,Van Mileghem, Seger,Verschueren, Rik H.
supporting information, p. 5782 - 5787 (2021/07/12)
An efficient, scalable and sustainable method for the quantitative deprotection of thetert-butyl carbamate (N-Boc) protecting group is described, using down to near-stoichiometric amounts of hydrogen chloride gas in solvent-free conditions. We demonstrate theex situgeneration of hydrogen chloride gas from sodium chloride and sulfuric acid in a two-chamber reactor, introducing a straightforward method for controlled and stoichiometric release of HCl gas. The solvent-free conditions allow deprotection of a wide variety ofN-Boc derivatives to obtain the hydrochloride salts in quantitative yields. The procedure obviates the need for any work-up or purification steps providing an uncomplicated green alternative to standard methods. Due to the solvent-free, anhydrous conditions, this method shows high tolerance towards acid sensitive functional groups and furnishes expanded functional group orthogonality.
Amino acid benzyl ester hydrochloride salt preparation method
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Paragraph 0047-0049, (2018/03/13)
The present invention discloses a preparation method for amino acid benzyl ester hydrochloride. The method comprises: by taking a metal chloride as a catalyst, in a suitable solvent, firstly generating amino acid hydrochloride by amino acid and hydrogen chloride; and then, esterifying the amino acid hydrochloride with benzyl alcohol at a reflux temperature, wherein water generated is removed by azeotrope; promoting esterification reaction; after the reaction is completed, filtering a thermal reaction liquid to remove the catalyst; removing a low-boiling-point substance (solvent) under low pressure; and performing post-treatment processes such as recrystallization and the like, thereby obtaining the object product, namely amino acid benzyl ester hydrochloride. Recrystallized mother liquor is recycled for more than 5 times. The method has advantages of relatively low raw material cost, relatively high conversion rate, relatively simple post-treatment, no use of chlorinating agents such as thionyl chloride and the like, less three waste emission, and the like, and is suitable for industrial production.
Substrate Fragmentation for the Design of M. tuberculosis CYP121 Inhibitors
Kavanagh, Madeline E.,Gray, Janine L.,Gilbert, Sophie H.,Coyne, Anthony G.,McLean, Kirsty J.,Davis, Holly J.,Munro, Andrew W.,Abell, Chris
supporting information, p. 1924 - 1935 (2016/10/06)
The cyclo-dipeptide substrates of the essential M. tuberculosis (Mtb) enzyme CYP121 were deconstructed into their component fragments and screened against the enzyme. A number of hits were identified, one of which exhibited an unexpected inhibitor-like binding mode. The inhibitory pharmacophore was elucidated, and fragment binding affinity was rapidly improved by synthetic elaboration guided by the structures of CYP121 substrates. The resulting inhibitors have low micromolar affinity, good predicted physicochemical properties and selectivity for CYP121 over other Mtb P450s. Spectroscopic characterisation of the inhibitors′ binding mode provides insight into the effect of weak nitrogen-donor ligands on the P450 heme, an improved understanding of factors governing CYP121–ligand recognition and speculation into the biological role of the enzyme for Mtb.
