Chiral Synthesis of Natural (+)-endo-Brevicomin with Enzymatic Reaction from l-Tartaric Acid

Full text of DOI:10.1002/bkcs.11893

Communication
DOI: 10.1002/bkcs.11893
BULLETIN OF THE
G. B. Gwon et al.
KOREAN CHEMICAL SOCIETY
Chiral Synthesis of Natural (+)-endo-Brevicomin with Enzymatic
Reaction from L-Tartaric Acid
*
Gi Baek Gwon, Hwan Gyu Jung, and Young Bae Seu
School of Life Sciences and Biotechnology, Kyungpook National University, Daegu, Republic of Korea.
*E-mail: ybseu@knu.ac.kr
Received January 23, 2019, Accepted September 28, 2019
Keywords: (+)-endo-Brevicomin, L-Tartaric acid, Enzyme reaction, Inversion chiral center, Total
synthesis
Dendroctonus brevicomis is a serious damaging pest to
pine forest of the southwestern United States, west coast of
North America and also Norway spruce.1 Use of phero-
mone is a safer way to control pest than that of insecticides.
It has several features such as being active at very low con-
centration, non-toxic, and species-specific. Accordingly,
synthesis of insect pheromones has been important.
(+)-endo-Brevicomin (1), structurally known as (1R,5S,7S)-
89% yield. Treating diol 5 with butyric anhydride in pyri-
dine provided dibutanoate 6 in a high yield (96%). Lipase
TOYOBO (LIP-301) which have been found optimizing
selective hydrolysis was applied to provide mono-hydroxy
ester 7 in 90% yield.15,16 Deprotection of acetonide in eight
was carried out under as mild conditions as 15% AcOH to
provide triol 8 in 82% yield. To protect the 1,2-hydroxy
groups of triol, 1,2-acetonide protection was conducted by
using p-TsOH in acetone in 64% yield. It appeared higher
yield in low temperature than room temperature. The free
hydroxy group of alcohol 9 was conducted mesylation with
MsCl and triethylamine as base furnished the mesylate 10
in 97% yield.
For inversion of chiral center, epoxide ring formation of
mesylate 10 using KOH in MeOH finally obtained (2S,3R)-
3,4-epoxy-1,2-O-isopropylidenebutane-1,2-diol 11 as a key
chiral building block in 90% yield. Stereochemical configu-
ration of 11 was identified from the comparison of the opti-
cal rotation value with a reported one.17
7-ethyl-5-methyl-6,8-dioxabicyclo[3.2.1]octane,
is
the
aggregation pheromone of bark beetles, D. brevicomis
(Figure 1).2 But, (−)-endo-Brevicomin significantly reduces
the response of beetles.3 Because of interesting biological
activities of brevicomins, various synthetic approaches have
been reported.1,4–10
The chiral epoxide (2S,3R)- or (2R,3S)-3,4-epoxy-1,2-O-
isoproplidenebutane-1,2-diol (11) has four carbon-skeleton
and two stereochemically defined chiral centers at C-2 and
C-3, and has been utilized as an enantiomerically enriched
synthetic starting material. A biologically active substance
such as bestatin and pheromone could be synthesized from
this C-4 synthon. Synthesis of (2S,3R)-3,4-epoxy-1,2-O-
isopropylidenebutane-1,2-diol 11 from L-ascorbic acid and
D-isoascorbic acid was reported.11 (2R,3R)-Tartaric acid (2)
is a chiral pool material of the C-4 skeleton and easy to get
in nature. Several methods of synthesis of exo-brevicomin
had been reported using L-(+)-tartaric acid 2.12,13 However,
endo-brevicomin has not been reported.14 This research
described that synthesis of (2S,3R)-3,4-epoxy-1,2-O-iso-
propylidenebutane-1,2-diol 11 via enzyme-mediated
regioselective hydrolysis and inversion of one stereogenic
center of the two chiral centers from L-tartaric acid 2. It also
described synthesis of optically selective (+)-endo-
brevicomin.
Our synthetic strategy to synthesize (+)-endo-brevicomin
1
from (2S,3R)-3,4-epoxy-1,2-O-isopropylidenebutane-
1,2-diol 11 is shown in Scheme 2. To add the carbon
frame, Grignard reaction with Li2CuCl4 of epoxide 11 with
C4H7MgBr provided alcohol 12 in 60% yield. Acetonide
was hydrolyzed in acidic condition to provide triol 13 in
97% yield. The triol 13 was converted into monotosylate
14 with p-TsCl in the presence of pyridine and
triethylamine in 61% yield. Methylation of tosylate 14 with
methylmagnesium bromide in Et2O afforded diol 15 in
70% yield. Finally, Wacker oxidation18 of diol 15
We established a route to 11 which is useful chiral inter-
mediate in nine steps from (2R,3R)-2 as shown in Scheme 1.
First, carboxyl groups were esterified to give 3. Diethyl-L-
(+)-tartrate 3 was synthesized by acid-catalyzed esterifica-
tion of starting material L-(+)-tartaric acid 2 in EtOH in
88% yield. Acetalization of diethyl-L-(+)-tartrate 3 with
2,2-dimethoxypropane furnished protected form 4 in 88%
yield. The diester 4 was reduced to diol 5 by using LAH in
Figure 1. Structure of the (+)-endo-brevicomin 1.
Bull. Korean Chem. Soc. 2019
© 2019 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Wiley Online Library
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BULLETIN OF THE
KOREAN CHEMICAL SOCIETY
important chiral building block to synthesize biologically
active substance. Using this, we expect this simple optically
selective synthetic approach to insect pheromone to be use-
ful in insect pheromone trap industry.
Acknowledgments. This research was supported by the
Kyungpook National University Research Grant.
Supporting Information. Additional supporting informa-
tion may be found online in the Supporting Information
section at the end of the article.
Scheme
1.
Synthesis
of
(2S,3R)-3,4-epoxy-1,2-O-iso-
propylidenebutane-1,2-diol 11. (a) H2SO4, EtOH, 88%; (b) 2,-
2-dimethoxypropane, p-TsOH, benzene, 88%; (c) LAH, Et2O,
89%; (d) Pr(CO)2O, DMAP, pyridine, 96%; (e) TOYOBO lipase,
pH 6.4 phosphate buffer, 90%; (f) 15% AcOH, 82%; (g) p-TsOH,
acetone, 64%; (h) MsCl, TEA, CH2Cl2, 97%; (i) KOH, MeOH,
H2O, 90%.
References
1. K. Mori, Y.-B. Seu, Tetrahedron 1985, 41, 3429.
2. R. M. Silverstein, R. G. Brownlee, T. E. Bellas, D. L. Wood,
L. E. Browne, Science 1968, 159, 889.
3. J. P. Vité, R. F. Billings, C. W. Ware, K. Mori,
Naturwissenschaften 1985, 72, 99.
4. B. Oehlschlager, D. Johnston, Am. Chem. Soc. 1987, 52, 940.
5. R. A. Fernandes, P. Kattanguru, V. Bethi, RSC Adv. 2014, 4,
14507.
6. S.-G. Kim, T.-H. Park, B. J. Kim, Tetrahedron Lett. 2006,
47, 6369.
7. K. Mori, Biosci. Biotechnol. Biochem. 2011, 75, 976.
8. P. Pal, A. K. Shaw, Tetrahedron 2011, 67, 4036.
9. S. Singh, P. J. Guiry, J. Org. Chem. 2009, 74, 5758.
10. S. D. Burke, N. Müller, C. M. Beaudry, Org. Lett. 1999,
1, 1827.
Scheme 2. Synthesis of (+)-endo-brevicomin 1. (a) C4H7MgBr,
Li2CuCl4, THF, 60%; (b) HCl, MeOH, 97%; (c) p-TsCl, pyridine,
TEA, CH2Cl2, 61%; (d) (CH3)2CuLi, Et2O, 70%; (e) PdCl2,
CuCl2, 1,2-dimethoxyethane, 62%.
11. Y. Le Merrer, C. Gravier-Pelletier, J. Dumas, J. C. Depezay,
Tetrahedron Lett. 1990, 31, 1003.
12. K. Mori, Tetrahedron 1974, 30, 4223.
13. K. R. Prasad, P. Anbarasan, Tetrahedron Asymmetry 2005,
16, 3951.
14. L. Ann, Chem. 1988, 12, 1135.
15. Y.-B. Seu, T.-K. Lim, C.-J. Kim, S.-C. Kang, Tetrahedron
Asymmetry 1995, 6, 3009.
employing PdCl2 and CuCl2 as catalyst
in
1,2-dimethoxyethane successfully obtained (+)-endo-
25
brevicomin 1 in 62% yield, ½αꢀD = +78.8 (c = 1.0, Et2O).
The spectral data of 1 was identified from the comparison
of the optical rotation value with a reported data.5,9 For
more detailed synthesis methods to the supporting informa-
tion Appendix S1.
16. W. H. Lee, I. H. Bae, B. M. Kim, Y.-B. Seu, Bull. Kor.
Chem. Soc. 2016, 37, 1910.
In summary, we achieved a facile synthesis of (+)-endo-
brevicomin 1 in 14 steps including enzyme-mediated selec-
tive monohydrolysis, alkylation and Wacker oxidation from
L-(+)-tartaric acid 2. The epoxide 11 has been used
17. M. Pottie, J. Van der Eycken, M. Vandewalle, H. Röper, Tet-
rahedron Asymmetry 1991, 2, 329.
18. K. Machiya, I. Ichimoto, M. Kirihata, H. Ueda, Agric. Biol.
Chem. 1985, 49, 643.
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