V. Rolland-Fulcrand et al. / Tetrahedron: Asymmetry 11 (2000) 4719–4724
4723
3
.5. (S)-i-Triazolylalanine 3b synthesis
R)-N-Acetyl-b-triazolylalanine 4b precipitated and (S)-b-triazolylalanine 3b was soluble at
(
−
1
pH 4 and 0°C in a 0.2N HCl solution. The concentration of products was around 50 g l .
The separation of both products was carried out by simple filtration. The (S)-b-triazolylala-
nine solution was concentrated under reduced pressure. The (R)-N-acetyl-b-triazolylalanine 4b
precipitated again and this procedure was repeated until one spot appeared by TLC or one
1
peak in chiral chromatography. [h] =−25 (c=10 H O); mp=233–234°C. H NMR (D O): l
D
2
2
ppm 4.25 (t, 1H, J=4.30 Hz); 4.8 (d, 2H, CH , J=4.25 Hz); 8.12 (s, 1H); 8.45 (s, 1H). ESI:
2
+
[
M+H] =157. Anal. calcd for C H N O , 1.5 H O, C, 32.8; H, 6.0; N, 30.6; found: C, 33.06;
5
8
4
2
2
H, 5.6; N, 31.0.
+
The purity of (S)-b-triazolylalanine was checked by chiral HPLC on Crown Pack CR
column optimized conditions: wavelengh=200 nm; flow=0.2 ml min ; pH=1.7 (HClO /
−
1
4
milliQ H O); elution at 0°C.
2
Retention time
(R)-N-Ac-b-Triazolylalanine 1b
(S)-b-Triazolylalanine 3b
(R)-b-Triazolylalanine 5b
7.0 min
5.0 min
6.0 min
3
.6. (S)-7-Azaindolylalanine 3c
The Michael addition was slower than with pyrazole a or triazole b and during the addition
the aminoester intermediate appears clearly on TLC [R =0.35 in ethyl acetate/diethyl ether
f
(
1/1)]. The reaction was stopped after 48 h at 60°C with the disappearance of the methyl-2-
acetamidoacrylate followed by TLC in ethyl acetate (R =0.85). The solvent was evaporated
f
under reduced pressure and the residue was chromatographed on silica gel in ethyl acetate/
diethyl ether (1/1) as eluent. The (RS)-N-acetylazaindolylalanine methyl ester (15%) and (RS)-
1
N-Ac-7-azaindolylalanine 1c (78%) were characterized by H NMR. The enzymatic hydrolysis
of 1c by Aspergillus sp. acylase was quantitative and the (S)-amino acid was easily obtained in
+
3
7% yield. [h] =−10 [c=10 H O/HCl (3N)]; ESI: [M+H] =206. Anal. calcd for C H N O ,
D
2
10 11
1
3
2
C, 58.5; H, 5.4; N, 20.5; found: C, 57.9; H, 5.2; N, 21.0; mp=278–280°C. H NMR
DMSO-d ) l ppm: 3.75 (dd, 1H, J=6.5 Hz and 3.25 Hz); 4.4 (dd, 1H, J=13.8 Hz and 6.5
(
6
Hz); 4.85 (dd, 1H, J=13.8 Hz and 3.25 Hz); 6.5 (d, 1H, J=3.4 Hz); 7.15 (dd, 1H, J=7.9 Hz
and 4.7 Hz); 7.6 (d, 1H, J=3.25 Hz); 8 (d, 1H, J=7.9 Hz); 8.3 (d, 1H, J=3.25); the purity of
+
(
S)-7-azaindolylalanine was checked by chiral HPLC on Crown Pack CR column optimized
−
1
conditions: wavelengh=200 nm; flow=0.5 ml min ; pH=2 (HClO /milliQ H O); elution at
4
2
0
°C.
Retention time
15 min
9.9 min
(R)-N-Ac-b-Azaindolylalanine 4c
(S)-b-Azaindolylalanine 3c
(R)-b-Azaindolylalanine 5c
12 min