Tetrahedron Letters
Enantioselective biomimetic transamination of
a-keto acids catalyzed by
H4-naphthalene-derived axially chiral biaryl pyridoxamines
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Chengkang Hou, Guoqing Zhao , Dongfang Xu, Baoguo Zhao
The Education Ministry Key Lab of Resource Chemistry and Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Asymmetric biomimetic transamination is a highly attractive method for synthesis of chemically and bio-
logically important chiral amino acids and chiral amines. Development of chiral pyridoxamines/pyridox-
als is the key for the reaction. New axially chiral biaryl pyridoxamines based on H4-naphathene skeleton
have been developed. The pyridoxamines display good enantioselectivity and high catalytic activity in
Received 27 November 2017
Revised 26 January 2018
Accepted 29 January 2018
Available online 9 February 2018
asymmetric biomimetic transamination of
a-keto acids, affording various optically active unnatural
amino acids in 61–98% yields with up to 91% ee’s.
Keywords:
Ó 2018 Elsevier Ltd. All rights reserved.
Biomimetic catalysis
Biomimetic transamination
Chiral pyridoxal pyridoxamine
Enzyme mimicking
Amino acid
Chiral
a
-amino acids are one type of the most important
catalytic activity and the best enantioselectivity in asymmetric
transamination of
-keto acids among the catalysts developed.15c
The axially chiral biaryl skeleton probably accounts for its good
catalytic performance. In order to pursue more efficient catalysts
for asymmetric biomimetic transamination, we developed new
molecules.1,2 They not only serve as basic building units of proteins
but also are widely present in various biologically active molecules
such as natural product Vancomycin,3 antiasmatic drug FK-888,4
and antitumor drug Abarelix5 (Scheme 1).1 In biological systems,
a
enzymatic transamination of
thesize various chiral
-amino acids.6 The reaction is catalyzed by
the coenzyme pyridoxal/pyridoxamine phosphates, i.e. vitamin B6
(Scheme 2).6,7 Pyridoxamine phosphate (PMP) condenses with
a
-keto acids is the main way to syn-
axially chiral biaryl pyridoxamines
hydrogenated naphthalene moiety (Scheme 3) and also
investigated 4-catalyzed asymmetric transamination of
acids. Herein, we report our studies on this project.
4
containing partially
a
a-keto
a
-
keto acid 1 to form a ketimine intermediate, which then undergoes
asymmetric 1,3-H shift and subsequent hydrolysis to give chiral
amino acid 2 and generate pyridoxal phosphate (PLP). The catalyst
pyridoxal is re-converted back to pyridoxamine (PMP) by amine
source 20 via a reverse transamination process, completing a cat-
alytic cycle. Mimicking the biological process with chiral pyridox-
als/pyridoxamines8–14 as the catalyst provides an attractive
strategy for the synthesis of chiral amino acids. The pyridoxal/pyri-
doxamine catalyst plays a crucial role in asymmetric biomimetic
transamination in terms of activity and enantioselectivity.
Recently, we have developed several chiral pyridoxal/pyridoxam-
ine catalysts and also have realized the corresponding catalytic
asymmetric biomimetic transamination for the first time.15 It has
been found that chiral pyridoxamine 3 displays the highest
The synthesis of chiral pyridoxamines 4 started with Pd-cat-
alyzed Suzuki coupling of pyridyl bromide 5 and H4-naphthyl
boronic acid 6 to give dialdehyde 7 in 31% yield, building the skele-
ton of the catalyst (Scheme 4). Selective formation of imine with
(S)-tert-butanesulfinamide followed by reduction with NaBH4
formed a pair of chromatographically separable diastereomers (R,
S)-8 and (S,S)-8. The absolute configurations of the diastereomers
were determined by X-ray analysis of the oxime derivative [(S,S)-
9-oxime] of compound (S,S)-9,16 which was obtained from (S,S)-8
by oxidation with MnO2 and subsequent condensation with
hydroxylamine (Fig. 1). Compound (R,S)-8 then underwent oxida-
tion with MnO2, reductive amination, and deprotection to give
the desired chiral pyridoxamines 4a-e as HCl salts.
By using 5 mol% of chiral pyridoxamine 4a as the catalyst and
2,2-diphenylglycine (11)17–19 as the amine source, transamination
of
a-keto acid 1a was optimized (Table 1). The transamination in
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Corresponding authors.
ethanol and water (8:2) displayed the highest enantioselectivity
(Table 1, entry 2 vs 1 and 3–10). A certain amount of water seems
(B. Zhao).
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