Molecules 2005, 10
1027
Reduction of 9 with magnesium and methanol gave the saturated nitrile, which was further
reduced with DIBAL to give aldehyde 10 (Figure 7). The remaining two carbons were attached to 10
by Grignard and Wittig reactions, respectively, to give 1 as a stereoisomeric mixture. The mixture
could be separated by preparative GC, and a fraction with a retention time of 54.3 min showed an
NMR spectrum identical with that of the natural product. The pheromone must be a stereoisomer of 1.
But how about the stereochemistry of that isomer?
Figure 8
Comparison of the Characteristic Spectral Data between Natural
Product and Its Diastereoisomers
Table 1. Characteristic 1H NMR data (δ/ppm)
1
7
5
4
13
1R*,4S*,5S*2a) 1R*,4R*,5S*3) 1R*,4S*,5R*4)
natural1)
1R*,4R*,5R*
no
4.61 (d)
4.82 (br.s)
5.31 (m)
4.62 (s)
4.83 (s)
5.32 (m)
4.72 (s)
4.83 (t)
5.33 (br.t)
4.60 (br.s)
4.75 (br.s)
5.25 (m)
13-Ha
13-Hb
7-H
data
available
natural1): [α]D = +37.1 (c = 12, hexane)
1R,4S,5S : [α]D25 = –39.6 (c = 0.3, hexane)2b)
1) S. Tebayashi, N. Hirai, S. Matsuyama, T. Suzuki, H. Nakakita, T. Nemoto, H. Nakanishi,
J. Stored Prod. Res. 1998, 34, 99.
2a) W. Oppolzer, F. Zutterman, K. Bättig, Helv. Chim. Acta, 1983, 66, 522.
2b) D. Solas, J. Wolinsky, J. Org. Chem., 1983, 48, 670.
3) S. Kurosawa, M. Bando, K. Mori, Eur. J. Org. Chem., 2001, 4395.
4) B. Tomita, T. Isono, Y. Hirose, Tetrahedron Lett., 1970, 1371.
At this stage Dr. Tashiro surveyed the literature through SciFinder, and collected the NMR data of
the stereoisomers of acoradiene (Figure 8). This table shows the chemical shift values of the olefinic
protons of the acoradiene stereoisomers. Although the (1R,4R,5R)-isomer was unknown, the data of
other three stereoisomers could be compared with those of the pheromone. The δ-values of the natural
pheromone were in good accord with those of (1R,4S,5S)-isomer. In 1983 Wolinsky had reported the
specific rotation of that isomer to be –39.6, while that of the natural pheromone was +37.1. The natural
pheromone therefore must be (1S,4R,5R)-isomer. This conclusion has to be proven by a synthesis.
Figure 9
Retrosynthetic Analysis
T. Tashiro, S. Kurosawa, K. Mori, Biosci. Biotechnol. Biochem. 2004, 68, 663.
O
O
(1S,4R,5R)-1
A
B
O
O
O
O
O
O
O
CO2Me
O
O
C
E
(S)-(–)-Pulegone [(S)-2]
D
cf. D. Solas, J. Wolinsky, J. Org. Chem., 1983, 48, 670.