Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 4407–4409
Preparation of 2,3-diaminopropionate from ring opening
of aziridine-2-carboxylate
b
b
c
Yongeun Kim,a Hyun-Joon Ha,a,b, Kyusung Han, Seung Whan Ko, Hoseop Yun,
*
Hyo Jae Yoon,d Min Sung Kimd and Won Koo Leeb,d,
*
aDepartment of Chemistry, Hankuk University of Foreign Studies, Yongin 449-791, Korea
bImagene Co. Ltd, Biotechnology Incubating Center, Seoul National University, Seoul 151-742, South Korea
cDepartment of Molecular Science and Technology, Ajou University, Suwon 442-749, South Korea
dDepartment of Chemistry, Sogang University, Seoul 121-742, South Korea
Received 26 February 2005; revised 6 April 2005; accepted 11 April 2005
Available online 10 May 2005
Abstract—Ring opening reaction of an enantiomerically pure aziridine-2-carboxylate with an azide nucleophile under aqueous
acidic media proceeded efficiently and stereoselectively to give 3-amino-2-azidopropionate which is converted to orthogonally
protected 2,3-diaminopropionate.
Ó 2005 Elsevier Ltd. All rights reserved.
The importance of enantiopure 2,3-diaminopropionate
can be found as a fragment of various biologically
important molecules such as roxifiban,1 cyclotheon-
amide2 and many potential drug candidates.3 An easy
access of 2,3-diaminopropionate or its synthetic precur-
sor would therefore promote the drug discovery pro-
gram. Additional utility of 2,3-diaminopropionate was
found recently as a probe to investigate the structure
of peptide and proteins.4 Thereby its large scale prepara-
tion is absolutely necessary to carry out the solid phase
peptide synthesis cooperating 2,3-diaminopropionate as
one of unnatural amino acids. Up to now only one syn-
thetic method is available starting from aspartic acid via
Curtius rearrangement as the core reaction including
many tedious protection and deprotection steps.2,5
Herein we would like to report a simple and efficient
method forthe synthesis of enantiopuer 2,3-diamino-
propionate from the regioselective ring opening reaction
of a commercially available chiral aziridine-2-carboxyl-
ate in high yield.
Since we reported the production of aziridine-2-carbox-
ylic acid (ꢀ)-menthol esterin industiral scale, we have
been interested in the preparation of diverse nitrogen
containing chiral molecules.6 Methods we developed
include manipulation of carboxylate group, ring expan-
sion and ring opening reaction with many different
nucleophiles such as oxygen, nitrogen, sulfur and
halides.6 Even though many examples of ring opening
reaction of activated aziridine by azide nucleophiles
were reported,7 it was not possible to produce 2,3-di-
aminopropionate by direct ring opening reaction of
aziridine-2-carboxylate with benzyl substituent on the
nitrogen due to its inertness towards external nucleo-
philes. In this report we would like to describe the
first direct ring opening reaction of N-benzylaziridine-
2-carboxylate with azide as a nitrogen nucleophile
underacidic aqueous media to give 3-amino-2-
azidopropionate.
Chiral [10(R)-a-methylbenzyl]aziridine-2(R)-carboxylate
(ꢀ)-menthol ester 1a was reacted in 50% aqueous
ethanol at pH 4.0, adjusted by addition of sulfuric acid,
with sodium azide in the presence of 10 mol% of
AlCl3Æ6H2O as a catalyst to yield the ring opening pro-
duct 2-azido-3-[10(R)-a-methylbenzylamino]-propionate
2a in 95% yield (Scheme 1).
Keywords: Ring opening; Azide; Aziridine-2-carboxylate; 2,3-Diamino-
propionate.
*
Corresponding authors. Tel.: +82 31 3304369 (H.-J.H); tel.: +82 1
sogang.ac.kr
The ring opening product 2a was then reacted with
methyl oxalyl chloride followed by catalytic hydrogenation
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.04.039