- Unwanted hydrolysis or α/β-peptide bond formation: How long should the rate-limiting coupling step take?
-
Nowadays, in Solid Phase Peptide Synthesis (SPPS), being either manual, automated, continuous flow or microwave-assisted, the reaction with various coupling reagents takes place via in situ active ester formation. In this study, the formation and stability of these key active esters were investigated with time-resolved 1H NMR by using the common PyBOP/DIEA and HOBt/DIC coupling reagents for both α- and β-amino acids. Parallel to the amide bond formation, the hydrolysis of the α/β-active esters, a side reaction that is a considerable efficacy limiting factor, was studied. Based on the chemical nature/constitution of the active esters, three amino acid categories were determined: (i) the rapidly hydrolyzing ones (t 24 h) in solution. The current insight into the kinetics of this key hydrolysis side reaction serves as a guide to optimize the coupling conditions of α- and β-amino acids, thereby saving time and minimizing the amounts of reagents and amino acids to be used-all key factors of more environmentally friendly chemistry.
- Goldschmidt G?z, Viktória,Nagy, Adrienn,Farkas, Viktor,Keszei, Ern?,Perczel, András
-
p. 30720 - 30728
(2019/10/28)
-
- Synthesis method of Fmoc-Arg(Pbf)-OH
-
Belonging to the technical field of arginine protection, the invention relates to a synthesis method of Fmoc-Arg(Pbf)-OH. The synthesis method of Fmoc-Arg(Pbf)-OH includes: first performing carboxyl esterification on arginine, then introducing a Boc group to protect amino thereon, introducing a Pbf group to guanidine, removing the Boc group, conducting saponification, and finally introducing a Fmoc group to the amino. According to the method for synthesis of Fmoc-Arg(Pbf)-OH, with only 1.1 times of Pbf-Cl, Arg can react totally, compared with the prior art that unreacted arginine still exists when the dosage of Pbf-Cl is 2 times that of arginine, the dosage of Pbf-Cl in the invention is greatly reduced, also no Arg residual exists, and the Pbf-Cl is expensive, therefore the cost is greatly reduced, thus being conducive to industrial popularization and application.
- -
-
Paragraph 0071; 0094-0096; 0097-0099
(2017/08/31)
-
- Synthesis of l -octaarginine through microencapsulated palladium-catalyzed allyl ester deprotection
-
Octaarginine has been described as a molecular transporter. We report a useful synthesis of orthogonally protected l-octaarginine by using a method based on a microencapsulated palladium catalyst. Known palladium-based methods for allyl ester deprotection have been modified to facilitate purification of the unprotected intermediates. This improvement in the purification step has also been tested with a variety of allyl α-amino esters and allyl α,β-unsaturated esters.
- Pérez-López, Ana M.,González-Calderón, Dávir,Occorso, Antonio,Galindo-ángel, Javier,Domínguez-Seglar, José F.,Tamayo, Juan A.,Díaz-Gavilán, Mónica,Gómez-Vidal, José A.
-
supporting information
p. 2319 - 2322
(2015/08/06)
-
- A one-pot procedure for the preparation of N-9-fluorenylmethyloxycarbonyl- α-amino diazoketones from α-amino acids
-
The study describes a new "one-pot" route to the synthesis of N-9-fluorenylmethyloxycarbonyl (Fmoc) α-amino diazoketones. The procedure was tested on a series of commercially available free or side-chain protected α-amino acids employed as precursors. The conversion into the title compounds was achieved by masking and activating the α-amino acids with a single reagent, namely, 9-fluorenylmethyl chloroformate (Fmoc-Cl). The resulting N-protected mixed anhydrides were reacted with diazomethane to lead to the α-amino diazoketones, which were isolated by flash column chromatography in very good to excellent overall yields. The versatility of the procedure was verified on lipophilic α-amino acids and further demonstrated by the preparation of N-Fmoc-α-amino diazoketones also from α-amino acids containing side-chain masking groups, which are orthogonal to the Fmoc one. The results confirmed that tert-butyloxycarbonyl (Boc), tert-butyl (tBu), and 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl (Pbf), three acid-labile protecting groups mostly adopted in the solution and solid-phase peptide synthesis, are compatible to the adopted reaction conditions. In all cases, the formation of the corresponding C-methyl ester of the starting amino acid was not observed. Moreover, the proposed method respects the chirality of the starting α-amino acids. No racemization occurred when the procedure was applied to the synthesis of the respective N-Fmoc-protected α-amino diazoketones from l-isoleucine and l-threonine and to the preparation of a diastereomeric pair of N-Fmoc-protected dipeptidyl diazoketones.
- Siciliano, Carlo,De Marco, Rosaria,Guidi, Ludovica Evelin,Spinella, Mariagiovanna,Liguori, Angelo
-
p. 10575 - 10582
(2013/02/22)
-
