Biomimetic Peptide Catalytic Bond‐Forming Utilizing a Mild Brønsted Acid

Abstract

Since the global peptide drug market demand has been predicted to increase, highly efficient and inexpensive mass scale peptides are required. However, the production process raises questions about the cost of energy input, scaleup production, raw materials, and solvents treatment. This paper introduces 2 methods for the 2-4 mer oligopeptides bond formation for batch reaction utilizing 50-100 mol% of a mild Brønsted acid under the mild condition. One of the methods has been capably adapted to flow synthesis at room temperature using organic solvents with boiling points below 100 °C. The method applies the tert-butoxycarbonyl amino methoxy group, forming the desired dipeptide without solvent at mild temperatures. Furthermore, the conversion of the carboxylic acid leaving the group to phenyl ester promotes peptide bond formation, and the reaction were applied to di, tri, and tetrapeptide bond formation in excellent yield without notable racemization at ambient temperature (up to > 99 % yield and 99 : 1 dr). Finally, this study proposes this new production method to overcome the limited scale-up production by reaction device scale: liquid phase biomimetic catalytic peptide flow synthesis utilizing a mild Brønsted acid.

Design and Synthesis of d-Ala-d-Ala Silica Gel for a Binding Mode-Based Physicochemical Screening Method

“…Immobilization of d -Ala- d -Ala derivative 4 and NH-silica gel 3 progressed via N -alkylation. d -Ala- d -Ala derivative 4 would be obtained by amidation with bromo acetic acid ( 5 ) from known compound 6 . Our synthesis commenced with amidation of 6 with 5 using the peptide coupling condition (Scheme ).…”

An Unusual Acceleration of Amination Reactivity by the Proximal Ester Groups in Catechol Diesters: An Efficient Way for Peptide Synthesis

“…In 1981, Vellaccio and Kemp pointed out that the basicity of the oxygen was decreased when the benzene ring was substituted with a nitro group and made it less effective at anchimeric assistance . Our group has reported an intermolecular Brønsted acid assistance peptide bond formation strategy recently . Therefore, we cannot rule out the possibility of the intermolecular Brønsted acid catalysis (path II-b).…”

“…20 Our group has reported an intermolecular Brønsted acid assistance peptide bond formation strategy recently. 41 Therefore, we cannot rule out the possibility of the intermolecular Brønsted acid catalysis (path II-b). We believed that the path IIa and path II-b both existed in the reaction.…”

A practical approach for oligopeptide synthesis via synergistic photoredox, cobaloxime and organophosphorus triple catalysis

“…3 The increasing requirements of reducing carbon emissions and the immensely growing demand in the pharmaceutical industry have propelled the development of sustainable methods for peptide synthesis with higher efficiency and selectivity. 4–7 In this regard, Yamamoto and coworkers demonstrated the combination of HSi[OCH(CF 3 ) 2 ] 3 and N -( tert -butyldimethylsilyl)- N -methyltrifluoroacetamide (MTBSTFA) for the one-pot formation of dipeptides via an intriguing disilyl intermediate as the reactive intermediate (Scheme 1A, path a). 6 Tangible success has also been obtained with electrophilic ynamides and allenones via the formation of vinyl ester intermediates as active esters (Scheme 1A, path b and c, respectively).…”