Diisopropylethylamine eliminates dipeptide formation during the acylation of amino acids using benzoyl chloride and some alkyl chloroformates

Abstract

Acylation of amino acids using benzoyl chloride in aqueous alkali leads to benzoylamino acids containing one percent of benzoyldipeptide. Use of diisopropylethylamine instead of sodium hydroxide as base eliminates the side reaction responsible for the contaminant. Ethoxycarbonylamino acids are advantageously prepared in the same manner using ethyl chloroformate or diethyl dicarbonate. The latter gives rise to some N-substituted dipeptide when used in aqueous alkali. The method is unsatisfactory for the benzyloxycarbonylation of amino acids. Use of 9-fluorenylmethyl chloroformate and diisopropylethylamine gives the pure derivative of leucine in moderate yield.

4-[4-[(2-Hydroxybenzoyl)amino]phenyl]butyric Acid as a Novel Oral Delivery Agent for Recombinant Human Growth Hormone

“…Synthetic Procedures. The compounds listed in Table were prepared by standard techniques − in either aqueous or organic solvents. In general, aqueous reaction conditions included the dissolution of a non-α-amino acid in aqueous sodium hydroxide followed by the addition of the appropriate acid chloride.…”

Microsphere Formation in a Series of Derivatized .alpha.-Amino Acids: Properties, Molecular Modeling, and Oral Delivery of Salmon Calcitonin

“…All of the compounds that were prepared in our laboratory have been reported previously. [21][22][23][24][25][26][27][28][29][30][31][32] Microsphere Formation. In order to investigate the role of structure in molecular self-assembly, we examined the microsphere-forming abilities of each derivatized amino acid individually using a light microscope at both 10-and 100-fold magnification as described in the Experimental Section of this paper.…”

“…The results reveal, in contrast to the previously described series of compounds, that acylated phenylalanines having a calculated log P >-2.0 do not necessarily form spheres. Thus, AT-methylphenylalanine ( 19), iV,iV-dimethylphenylalanine (20), IV-acetylphenylalanine amide (21 j, iV-formylphenylalanine (22), and IV-acetylphenylalanine (23) did not form micro- °Microspheres were examined using a light microscope at 10and 100-fold magnification. Ratings of 0-2 were given a "no" designation, and ratings of 3-5 were given a "yes" designation.…”

α‐N‐Protected dipeptide acids: a simple and efficient synthesis via the easily accessible mixed anhydride method using free amino acids in DMSO and tetrabutylammonium hydroxide

“…N ‐Ethoxycarbonyl‐ l ‐phenylglycine ( 1Eb ) and N ‐ethoxycarbonyl‐ dl ‐phenylglycine ( rac‐1Eb ) were prepared by reported procedure . All solvents and reagents were purchased from Aldrich Chemical Company and used without further purification.…”