Chemistry Letters 2001
381
shown in Scheme 2. As a result, it was found that the physical
(IR and H NMR) and chemical constants (mp and elemental
Finally, hydrolysis of the t-butyl ester of (1'R)-29 with TFA,
accompanying deprotection of the Boc group, followed by pro-
tection once more with Boc2O gave the corresponding free acid
derivative (1'R)-37, which was then coupled with the indepene-
dently prepared precursor of (P)-33 by the BOP method to give
first the protected Fragment A-B derivative (P)-2.9
1
analysis) were completely identical, but the signs of the specific
rotation were reversed. These facts clearly indicate that the
compounds 29 and 30 as well as 27 and 28 are diastereomeric
isomers; further, 31 and 32 are enantiomer to each other.
Furthermore, in order to determine the configuration of the
2-(1-aminoethyl) group of the synthetic 29 and 30, (R)- and (S)-
configurational 2-(1-aminoethyl)pyridines 36 were synthesized,
and the CD spectra of 36 were compared with those of 29 and
30.
In conclusion, a convenient synthetic method for the main
central 2,3,6-trisubstituted pyridine skeleton of 1 has been suffi-
ciently developed.
This work was supported in part by a Grant-in-Aid for
Scientific Research Nos. 10640532 and 12640529 from the
Ministry of Education, Science, Sports, and Culture, Japan.
References and Notes
1
M. Aoki, T. Othuka, M. Yamada, Y. Ohba, H. Yoshizaki, H.
Yasuno, T. Sano, and H. Seto, J. Antibiot., 44, 582 (1992).
C. Shin, Y. Nakamura, and K. Okumura, Chem. Lett., 1993, 1405.
C. Shin, A. Ito, K. Okumura, and Y. Nakamura, Chem. Lett., 1995,
45.
2
3
4
J. P. Sanches, T. F. Mich, and G. G. Huang, J. Heterocycl. Chem.,
31, 297 (1994).
5
6
dppp = 1,3-bis(diphenylphosphino)propane.
Y. Hamada, M. Shibata, T. Sugiura, S. Kato, and T. Shioiri, J. Org.
Chem., 52, 1252 (1087).
26
7
29: Colorless syrup. [α]D –50.9°(c 0.7, CHCl3). IR 3435, 3113,
2977, 2931, 2360, 1719, 1606, 1583 cm–1. 1H NMR (CDCl3) δ =
1.43 (s, 9H, Boc), 1.46 (d, 3H, CH3CH, J = 6.3 Hz), 1.53 (s, 9H,
But), 3.63 (d, 2H, CH2SCH, J = 9.2 Hz), 5.22 (t, 1H, CHN=C, J =
9.2 Hz), 5.39 (s, 2H, PhCH2), 5.62–5.89 (m, 2H, CHNH), 7.34–7.49
(m, 5H, Ph), 8.17 (s, 1H, pyridine ring-H, J = 8.3 Hz), 8.20 (s, 1H,
thiazole ring-H), 8.34 (d, 1H, pyridine ring-H, J = 8.3 Hz).
M. Takeshita, K. Terada, N. Akutsu, S. Yoshida, and T. Sato,
Heterocycles, 26, 3051 (1987).
Asymmetric reduction of 2-acetylpyridine (33) with Baker’s
Yeast gave (S)-2-(1-hydroxyethyl)pyridine 34, which was con-
verted to (1'R)-2-[1-(N-Boc)aminoethyl]pyridine 36 via (1'R)-(1-
azidoethyl)pyridine 35. The specific rotation value of 34 thus
26
obtained was [α]D –55.5° (c 1.6, EtOH) {lit.8 [α]D –55.5° (c
8
9
1.5, EtOH)}, showing high optical purity (96% ee). Similarly,
(S)-36 was also obtained from (S)-34 via successive (R)-34 and
(S)-35, as shown in Scheme 3.
The CD spectra of optically active 29 and (R)-36 showed
strong negative Cotton effects at 373 and 270 nm, respectively,
while those of 30 and (S)-36 showed positive Cotton effects in
the same region. Therefore, it could be determined that the
absolute structure of 29 was (R,S)-configuration and identical
with that of the natural 1.
22
(P)-2: Colorless syrup. [α]D +11.1°(c 0.3, CHCl3). IR 3389,
2929, 2333, 1715, 1684, 1582, 1489, 1438 cm–1
.
1H NMR
(CDCl3) δ = 0.93 and 0.95 (each s, 9H, TPS’s But), 1.29–1.65 (m,
12H, Boc, CH3CH), 3.62–3.85 (m, 4H, thiazoline’s CH2 × 2), 3.86
(s, 3H, OMe), 3.94–4.14 (m, 2H, CH2O), 4.32–4.40 (m, 1H,
CHCH2O), 5.28–5.39 (m, 2H, thiazoline’s CH × 2), 5.40 (s, 2H,
Bn’s CH2), 5.46–5.54 (m, 1H, CONH), 5.63–5.85 (m, 2H, BocNH,
CH3CH), 7.20–7.60 (m, 15H, TPS’s Ph × 2, Bn’s Ph), 7.98–8.10
(m, 3H, thiazole ring-H × 3), 8.15–8.34 (each d, 2H, pyridine ring-
H, J = 7.5 Hz).