Job/Unit: O43582
/KAP1
Date: 26-01-15 14:34:16
Pages: 9
Total Synthesis of Piperenol B
age at 4 °C. [α]2
CHCl
for (+)-9, –37.6 (c = 0.425, CHCl
0
= +52.91 (c = 0.425, CHCl
), +36.30 (c = 1.085,
D
3
), +16.92 (c = 1.000, MeOH) [ref.[6,7] +50 (c = 1.000, MeOH) [1] R. N. Patel, Biocatalysis in the pharmaceutical and biotechnol-
3
3
) for (–)-9]. CD: Δε237 = –12.19
ogy industries, CRC Press, Boca Raton, FL, 2008, p. 105–151.
[2] a) A. Liese, M. V. Filho, Curr. Opin. Biotechnol. 1999, 10, 595–
603; b) M. Gavrilescu, Y. Chisti, Biotechnol. Adv. 2005, 23,
471–499; c) J. Whittal, P. W. Sutton, Practical methods for bi-
ocatalysis and biotransformations 2, Wiley-VCH, Weinheim,
Germany, 2012, p. 1–5.
c = 0.1, MeOH), Δε221 = +4.36 (c = 0.1, MeOH) [ref.[ Δε237
Ͻ
and Δε215 Ͼ 0 for (+)-9; Δε237 = +21.1 (c, n.a., MeOH) and Δε221
–6.0 (c, n.a., MeOH) for (–)-9]. H NMR (400 MHz, CDCl
7.90–8.00 (m, 4 H), 7.50–7.53 (m, 2 H), 7.26–7.34 (m, 4 H), 6.13–
6,7]
(
0
=
=
1
3
): δ
6
.16 (m, 1 H), 6.04 (d, J = 9.84 Hz, 1 H), 5.70 (br. s, 1 H), 4.37–
.50 (dd, J = 9.90, J = 5.50 Hz, 2 H), 4.19 (s, 2 H), 2.70–3.27 (br.
): δ = 166.4, 166.3,
34.0, 133.3, 129.7, 129.6, 129.5, 128.5, 127.1, 71.6, 69.0, 68.8, 68.6,
7.1 ppm.
[
3] a) T. C. M. Fischer, H. G. Leisch, M. D. Mihovilovic, Monatsh.
Chem. 2010, 141, 699–707; b) M. D. Mihovilovic, H. G. Leisch,
K. Mereiter, Tetrahedron Lett. 2004, 45, 7087–7090.
4
1
2
13
m, 3 H) ppm. C NMR (100.6 MHz, CDCl
3
1
6
[
4] A. M. Reiner, G. D. Hegeman, Biochemistry 1971, 10, 2530–
2536.
[
5] a) S. E. Lewis, Chem. Commun. 2014, 50, 2821–2830; b) A. G.
Myers, D. R. Siegel, D. J. Buzard, M. G. Charest, Org. Lett.
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d) M. H. Parker, B. E. Maryanoff, A. B. Reitz, Synlett 2004,
[
(3aR,6S,7S,7aR,2ЈR)-6-Benzoyloxy-7-(3Ј,3,Ј3Ј-trifluoro-2Ј-meth-
oxy-2Ј-phenylpropanoyl)-2,2-dimethyl-7,7a-dihydrobenzo[1,3]dioxol-
a(6H)-yl]methyl Benzoate (10): N,N-Dicyclohexylcarbodiimide
DCC; 39 mg, 0.188 mmol) and DMAP (0.6 mg, 0.047 mmol) were
sequentially added to a solution of 8 (40 mg, 0.094 mmol) in dry
CH Cl (2 mL) at room temp. under N . Then a solution of (R)-
+)-α-methoxy-α-trifluoromethylphenylacetic acid [(R)-(+)-MTPA;
3
(
2095–2098; e) M. J. Palframan, G. Kociok-Köhn, S. E. Lewis,
Org. Lett. 2011, 13, 3150–3153; f) D. R. Adams, C. Aichinger,
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M. J. Palframan, G. Kociok-Köhn, S. E. Lewis, Chem. Eur. J.
2
2
2
(
3
2 2
3 mg, 0.141 mmol] in dry CH Cl (1 mL) was added dropwise and
2012, 18, 4766–4774; h) S. Pilgrim, G. Kociok-Köhn, M. D.
the resulting suspension was stirred at room temp. o/n. The reac-
tion mixture was concentrated under reduced pressure. Purification
Lloyd, S. E. Lewis, Chem. Commun. 2011, 47, 4799–4801; i)
J. A. Griffen, J. C. White, G. Kociok-Köhn, M. D. Lloyd, A.
Weels, T. C. Arnot, S. E. Lewis, Tetrahedron 2013, 69, 5989–
5997; j) D. R. Adams, J. van Kempen, J. R. Hudlický, T. Hud-
lický, Heterocycles 2014, 88, 1255–1274.
by flash chromatography on silica gel (n-hexane/Et
tom 90:10, v/v) followed by trituration of the pale-yellow oil with
n-hexane/Et O (99:1, v/v) gave 10 (35 mg, 0.055 mmol, yield: 58%)
as a colorless oil that solidified upon storage at 4 °C. H NMR
400 MHz, CDCl ): δ = 7.96 (d, J = 7.64 Hz, 2 H), 7.89 (d, J =
.64 Hz, 2 H), 7.55–7.58 (m, 2 H), 7.48 (d, J = 7.84 Hz, 2 H), 7.39–
.42 (m, 4 H), 7.17 (t, J = 7.76 Hz, 2 H), 7.04 (t, J = 7.36 Hz, 1
2
O from 100:0
2
1
[6] S. C. Taneja, S. K. Koul, P. Pushpangadan, K. L. Dhar, W. M.
Daniewski, W. Schilf, Phytochemistry 1991, 30, 871–874.
(
7
7
3
[7] C.-R. Zhang, S.-P. Yang, S.-G. Liao, Y. Wu, J.-M. Yue, Helv.
Chim. Acta 2006, 89, 1408–1416.
[
8] a) B. Zwaneburg, M. H. H. Nkunya, H. Weenen, N. J. Koyi, L.
Thijis, Phytochemistry 1991, 26, 2563–2565; b) N.-J. Sun, Y.-H.
Liao, S.-L. Xu, J. Dai, Y.-S. Zhen, M. Zhu, Phytochemistry
H), 6.05 (br. s, 1 H), 6.00 (br. s, 1 H), 5.92 (d, J = 10.56 Hz, 1 H),
.82 (d, J = 10.56 Hz, 1 H), 4.60 (d, J = 11.96 Hz, 1 H), 4.40 (d, J
5
=
3
1
1
6
4.32 Hz, 1 H), 3.76 (d, J = 11.96 Hz, 1 H), 3.56 (s, 3 H), 1.41 (s,
1
997, 45, 729–732; c) Y.-H. Liao, L.-Z. Xu, S.-L. Yang, J. Dai,
Y.-S. Zhen, M. Zhu, N.-J. Sun, Phytochemistry 1997, 45, 729–
32.
13
3
H), 1.32 (s, 3 H) ppm. C NMR (100.6 MHz, CDCl ): δ = 165.7,
65.6, 165.5, 133.4, 133.1, 131.9, 129.8, 129.6, 129.3, 129.2, 128.5,
28.3, 126.7, 126.3, 124.5, 121.7, 110.4, 78.7, 77.2, 73.2, 70.6, 67.5,
4.4, 55.9, 27.9, 27.3 ppm.
7
[9]
a) M. Furlan, M. J. Kato, Pure Appl. Chem. 2007, 79, 529–538;
b) J. T. Arnason, I. M. Scott, H. R. Jensen, B. J. R. Philogène,
Phytochem. Rev. 2008, 7, 65–75.
[
(3aR,6S,7S,7aR,2ЈS)-6-Benzoyloxy-7-(3Ј,3,Ј3Ј-trifluoro-2Ј-meth-
oxy-2Ј-phenylpropanoyl)-2,2-dimethyl-7,7a-dihydrobenzo[1,3]dioxol-
a(6H)-yl]methyl Benzoate (11): According to the procedure for 10
[10] J. A. Griffen, S. J. Kenwright, S. Abou-Shehada, S. Wharry,
T. S. Moody, S. E. Lewis, Org. Chem. Front. 2014, 1, 79–90.
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[
3
1995, 44, 10805–10816.
and using (S)-(–)-MTPA, compound 11 was obtained as a pale-
yellow oil (37 mg, 0.058 mmol, yield: 62%). H NMR (400 MHz,
CDCl
7
4
1
[12] G. N. Jenkins, D. W. Ribbons, D. A. Widdowson, A. M. Z. Sla-
win, D. J. Williams, J. Chem. Soc. Perkin Trans. 1 1995, 2647–
3
): δ = 7.98 (d, J = 7.64 Hz, 2 H), 7.89 (d, J = 7.64 Hz, 2 H),
.54 (q, J = 7.12 Hz, 2 H), 7.45–7.47 (m, 2 H), 7.36 (t, J = 7.64 Hz,
H), 7.19–7.21 (m, 3 H), 6.03 (br. s, 1 H), 5.93–5.96 (m, 2 H), 5.86
2655.
[
[
13] J. M. Seco, E. Quiñoá, R. Riguera, Chem. Rev. 2012, 112,
4603–4641.
(
3
m, 2 H), 4.67 (d, J = 11.84 Hz, 1 H), 4.62 (d, J = 5.4 Hz, 1 H),
14] a) J. A. Dale, D. L. Dull, H. S. Mosher, J. Org. Chem. 1969, 34,
.99 (d, J = 11.84 Hz, 1 H), 3.76 (d, J = 11.96 Hz, 1 H), 3.39 (s, 3
2543–2549; b) J. A. Dale, H. S. Mosher, J. Am. Chem. Soc.
1
3
H), 1.45 (s, 3 H), 1.39 (s, 3 H) ppm. C NMR (100.6 MHz,
CDCl ): δ = 165.9 (2ϫ), 165.8, 133.5, 133.3, 131.8, 130.0, 129.9
2ϫ), 129.7, 129.5, 128.7, 128.6, 127.6, 126.5, 120.8, 110.9, 79.4,
1
973, 95, 512–519; c) D. A. Allen, A. E. Tomaso, O. P. Priest,
3
J. Chem. Educ. 2008, 85, 698–700.
(
7
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J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J. M.
Millam, M. Klene, J. E. Knox, J. B. Cross, V. Bakken, C. Ad-
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A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Mar-
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7.4, 74.0, 71.3, 67.3, 64.9, 55.3, 28.3, 27.9 ppm.
Acknowledgments
The authors thank Prof. Robert Mach and Dr. Astrid Mach-Aigner
(
Vienna University of Technology) for access to the CD photome-
ter (Innovative Project RAKI-MINT, Vienna University of Tech-
nology), and Prof. Andrew G. Myers (Harvard University) for the
kind donation of the strain Ralstonia eutropha B9. B. C. expresses
his gratitude to the European Union (EU) for providing a travel
fellowship (Erasmus Program).
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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