7686
G. Mehta, K. Islam / Tetrahedron Letters 45 (2004) 7683–7687
1685; (j) Graham, A. E.; McKerrecher, D.; Davies, D. H.;
Taylor, R. J. K. Tetrahedron Lett. 1996, 37, 7445; (k)
Kamikubu, T.; Hiroya, K.; Ogasawara, K. Tetrahedron
Lett. 1996, 37, 499; (l) Liu, Z.; Li, H.; Chen, S. Huaxue
Xuebao 1997, 55, 611; (m) Johnson, C. R.; Miller, M. W.
J. Org. Chem. 1997, 62, 1582; (n) Yoshida, N.; Konno, H.;
Kamikubu, T.; Takahashi, M.; Ogasawara, K. Tetrahe-
dron: Asymmetry 1999, 10, 3849; (o) Barros, M. T.;
Maycock, C. D.; Ventura, M. R. Tetrahedron 1999, 55,
3233; (p) Barros, M. T.; Maycock, C. D.; Ventura, M. R.
Chem. Eur. J. 2000, 6, 3991; (q) Shimizu, H.; Okamura,
H.; Yamashita, N.; Iwagawa, T.; Nakatani, M. Tetrahe-
dron Lett. 2001, 42, 8649; (r) Genski, T.; Taylor, R. J. K.
Tetrahedron Lett. 2002, 43, 3573; (s) Tachihara, T.;
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M. Tetrahedron 2003, 59, 10159.
to solidify and was transformed into a single dimeric
product (ꢀ)-8 through a stereospecific intermolecular
Diels–Alder reaction.13 The spectral data for (ꢀ)-8 were
identical with that of the natural product but had a rota-
tion ([a]D ꢀ147, c 1.0, MeOH) opposite in sign to that of
the natural product (lit.3 [a]D +149.8, c 1.0, MeOH).7
Thus, the first synthesis of the antipode of the biologi-
cally potent natural product panepophenanthrin has
been achieved and its biological activity profile is being
evaluated.
In short, we have devised a simple enzyme mediated
strategy to access chiral building blocks for the synthesis
of a range of biologically active epoxyquinone natural
products from readily available starting materials. This
versatile approach has resulted in the short syntheses
of natural products (ꢀ)-phyllostine, (+)-epoxydon, (+)-epi-
epoxydon and (ꢀ)-panepophenanthrin.
3. Sekizawa, R.; Ikeno, S.; Nakamura, H.; Naganawa, H.;
Matsui, S.; Iinuma, H.; Takeuchi, T. J. Nat. Prod. 2002,
65, 1491.
4. (a) Lei, X.; Johnson, R. P.; Porco, J. A., Jr. Angew. Chem.,
Int. Ed. 2003, 42, 3913; (b) Moses, J. E.; Commeiras, L.;
Baldwin, J. E.; Adlington, R. M. Org. Lett. 2003, 5, 2987;
(c) Mehta, G.; Ramesh, S. S. Tetrahedron Lett. 2004, 45,
1985.
5. (a) Mehta, G.; Islam, K. Tetrahedron Lett. 2003, 44, 3569;
(b) Mehta, G.; Islam, K. Org. Lett. 2004, 6, 807; (c)
Mehta, G.; Pan, S. C. Org. Lett. 2004, 6, 811; (d) Mehta,
G.; Islam, K. Tetrahedron Lett. 2004, 45, 3611; (e) Mehta,
G.; Roy, S. Org. Lett. 2004, 6, 2389.
Acknowledgements
K.I. thanks CSIR, India for the award of a research fel-
lowship. This work was supported by the Chemical Biol-
ogy Unit of JNCASR at the Indian Institute of Science,
Bangalore. The lipase used in this study was a gift from
Dr. Y. Hirose of Amano Pharmaceutical Co. Ltd.,
Japan.
6. Cookson, R. C.; Crundwell, E.; Hill, R. R.; Hudec, J. J.
Chem. Soc. 1964, 9, 3062.
7. All new compounds were fully characterised on the basis
1
of IR, H NMR, 13C NMR, mass data. Spectral data of
References and notes
24
selected compounds: (ꢀ)-13: ½aꢂ : ꢀ19.1 (c 1.15, CHCl3);
1. (+)-Epoformin: (a) Yamamoto, I.; Mizuta, E.; Henmi, T.;
Yamano, T.; Yamatodani, S. J. Takeda Res. Lab. 1973,
32, 532; Scott, A. I.; Zamir, L.; Phillips, G. T.; Yalpani,
M. Bioorg. Chem. 1973, 2, 124; (+)-epiepoformin: (b)
Nagasawa, H.; Suzuki, A.; Tamura, S. Agr. Biol. Chem.
1978, 42, 1303; (ꢀ)-Theobroxide: (c) Nakamori, K.;
Matsuura, H.; Yoshihara, T.; Ichihara, A.; Koda, Y.
Phytochemistry 1994, 35, 835; Yoshihara, T.; Ohmori, F.;
Nakamori, K.; Amanuma, M.; Tsutsumi, T.; Ichihara, A.;
Matsuura, H. J. Plant Growth Reg. 2000, 19, 457; (ꢀ)-
phyllostine: (d) Sakamura, S.; Ito, J.; Sakai, R. Agr. Biol.
Chem. 1970, 34, 153; Sakamura, S.; Ito, J.; Sakai, R. Agr.
Biol. Chem. 1971, 35, 105; Kerr, K. A. Acta Crys. 1986,
C42, 887; (+)-epoxidon: (e) Close, A.; Mauli, R.; Sigg, H.
P. Helv. Chim. Acta 1966, 49, 204; Sakamura, S.; Niki, H.;
Obata, Y.; Sakai, R.; Matsumoto, T. Agr. Biol. Chem.
1969, 33, 698; (+)-epiepoxidon: (f) Nagasawa, H.; Suzuki,
A.; Tamura, S. Agr. Biol. Chem. 1978, 42, 1303; Sekiguchi,
J.; Gaucher, G. M. Biochem. J. 1979, 182, 445; (+)-
harveynone: (g) Nagata, T.; Hirrota, A. Biosci. Biotechnol.
Biochem. 1992, 56, 810.
2. For the total synthesis of (ꢀ)-phyllostine, (+)-epiepoxidon
and related natural products, see: (a) Ichihara, A.; Oda,
K.; Sakamura, S. Agr. Biol. Chem. 1971, 35, 445; (b)
Ichihara, A.; Oda, K.; Sakamura, S. Tetrahedron Lett.
1972, 5105; (c) Ichihara, A.; Oda, K.; Sakamura, S. Agr.
Biol. Chem. 1974, 38, 163; (d) Ichihara, A.; Kimura, R.;
Oda, K.; Sakamura, S. Tetrahedron Lett. 1976, 4741; (e)
Ichihara, A.; Moriyasu, K.; Sakamura, S. Agr. Biol. Chem.
1978, 42, 2421; (f) Teh-Wei Chou, D.; Ganem, B. J. Am.
Chem. Soc. 1980, 102, 7987; (g) Ichihara, A.; Kimura, R.;
Oda, K.; Moriyasu, K.; Sakamura, S. Agr. Biol. Chem.
1982, 46, 1879; (h) Ichihara, A. Synthesis 1987, 9, 207; (i)
Kamikubu, T.; Ogasawara, K. Tetrahedron Lett. 1995, 36,
1H NMR (300MHz, CDCl3): dD6.22 (s, 2H), 4.62 (dt, 1H,
J = 2.7, 9.9Hz), 4.42 (d, 1H, J = 9.9Hz), 3.57 (d, 1H,
J = 9.9Hz), 3.52 (dd, 1H, J = 3, 3.9Hz), 3.26 (d, 1H,
J = 3.9Hz), 3.17 (s, 1H), 2.92 (s, 1H), 2.32 (dd, 1H,
J = 3.3, 7.2), 1.44 (d, 1H, J = 9.3Hz), 1.37 (d, 1H,
J = 9.3Hz), 0.87 (s, 9H), 0.02 (s, 6H); 13C NMR
(75MHz, CDCl3): d 206.5, 136.9, 136.5, 69.4, 66.9, 62.7,
59.9, 54.6, 49.1, 46.1, 45.9, 44.9, 25.8 (3C), 18.2, ꢀ5.5,
ꢀ5.6; HRMS (ES) m/z calcd for C18H27O4SiK[M+K]+:
24
375.1394, found: 375.1400. (+)-14: ½aꢂD +24 (c 1.95, CHCl3);
1H NMR (300MHz, CDCl3): d 6.16–6.13 (m, 1H),
5.94–5.91 (m, 1H), 5.80 (dd, 1H, J = 3.0, 7.5), 4.32 (d,
1H, J = 9.9Hz), 3.60 (d, 1H, J = 9.6Hz), 3.40 (dd, 1H,
J = 2.7, 3.9Hz), 3.26 (d, 1H, J = 3.6Hz), 3.16 (s, 1H), 2.79
(s, 1H), 2.43 (dd, 1H, J = 3.3, 7.8Hz), 2.10 (s, 3H), 1.42 (d,
1H, J = 9.3Hz), 1.34 (d, 1H, J = 9.3Hz), 0.88 (s, 9H), 0.03
(s, 6H); 13C NMR (75MHz, CDCl3): d 205.3, 169.9, 136.1,
135.9, 69.3, 66.7, 61.7, 57.2, 54.4, 46.9, 46.6, 45.7, 44.9,
25.8 (3C), 21.26, 18.2, ꢀ5.5, ꢀ5.6; HRMS (ES) m/z calcd
for C20H30O5SiK[M+K]+: 417.1500, found: 417.1492. (+)-
25
5b: ½aꢂD +250 (c 1.40, EtOH); 1H NMR (300MHz,
CD3COCD3): d 6.72–6.69 (m, 1H), 4.92 (d, 1H,
J = 7.5Hz), 4.66–4.63 (m, 1H), 4.30–4.10 (m, 3H), 3.78–
3.76 (m, 1H), 3.40 (d, 1H, J = 3.6Hz); 13C NMR (75MHz,
CD3COCD3): d 194.35, 139.30, 137.07, 63.25, 59.0, 58.79,
54.1; HRMS (ES) m/z calcd for C7H8O4Na[M+Na]+:
25
179.0320, found: 179.0314. (+)-5a: ½aꢂD +98.0 (c 1.0, EtOH);
1H NMR (300MHz, CD3COCD3):
d 6.50 (d, 1H,
J = 1.8Hz), 4.91 (d, 1H, J = 7.5Hz), 4.80–4.77 (m, 1H),
4.24–4.06 (m, 3H), 3.80 (d, 1H, J = 3.0, 6.6Hz), 3.34
(d,1H, J = 4.2Hz); 13C NMR (75MHz, CD3COCD3): d
194.5, 141.4, 135.2, 65.5, 59.1, 55.0, 54.0; HRMS (ES) m/z
calcd for C7H8O4Na[M+Na]+: 179.0320, found: 179.0310.
24
(ꢀ)-4: ½aꢂD : ꢀ108 (c 1.61, EtOH); 1H NMR (300MHz,