Scheme 2 Reagents and conditions: i, K2CO3, CO2 (800 psi), 200 °C, 4 h; ii, BBr3, CH2Cl2, 278 °C to room temp. (72%, two steps); iii, 1-nitrohepta-
4,6-diene (5 equiv.), BTIB, THF (86%); iv, K2CO3, Me3OBF4, CH2Cl2 (100%); v, Ac2O, pyridine; vi, p-ClC6H4NCO, Et3N, C6H6, room temp., 36 h; vii,
NaOH, H2O–THF (84%, three steps); viii, H2, Pd/C, H3BO3, MeOH–THF–H2O (100%).
is facile and can be effected at any convenient stage; in fact, the
conversion 7 ? 19 has already been achieved in 60% yield. The
benzindanone 14 offers possibilities for modification into the C/
D non-aromatic analogues (e.g. 2, 3 and 4). Many obvious
problems remain before any of these antibiotics can be
synthesised, but we regard this short and flexible route to the
pentacyclic system15 as an important first step on the way to
members of the viridin family.
We thank the Natural Sciences and Engineering Research
Council of Canada for support of this work.
Notes and references
1 For a recent review, see J. R. Hanson, Nat. Prod. Rep., 1995, 12, 381.
2 M. M. Blight and J. F. Grove, J. Chem. Soc., Perkin Trans. 1, 1986,
1317.
3 T. J. Pecher, H-P. Weber and S. Kis, J. Chem. Soc., Chem. Commun.,
1972, 1061.
4 T. Okada, L. Sakuma, Y. Fukui, O. Hazeki and M. Ui, J. Biol. Chem.
1994, 269, 3563.
5 S. Sato, M. Nakada and M. Shibasaki, Tetrahedron Lett., 1996, 37,
6141.
6 S. Honzawa, T. Mizutani and M. Shibasaki, Tetrahedron Lett., 1999, 40,
311; C. A. Broka and B. Ruhland, J. Org. Chem., 1992, 57, 4888.
7 R. Carlini, K. Higgs, C. Older, S. Randhawa and R. Rodrigo, J. Org.
Chem., 1997, 62, 2330.
8 O. Baine, G. F. Adamson, J. W. Barton, J. L. Fitch, D. R. Swayampati
and H. Jeskey, J. Org. Chem., 1954, 19, 510. We thank Warren Wallace
for laboratory assistance with the preparation of 9.
9 The acid 9 had been previously prepared by the CuSO4 catalysed
reaction of 3-bromo-5-methylsalicyclic acid with NaOH: D. D. Weller
and E. P. Stirchak, J. Org. Chem., 1983, 48, 4873. We were unable to
obtain good yields of 9 by this method in spite of several attempts.
10 Prepared from 1-iodohepta-4,6-diene and silver nitrite in 68% yield; see
E. Vedejs, T. H. Eberlein and R. G. Wilde, J. Org. Chem., 1988, 53,
2220 for the synthesis of the iodide.
11 R. Carlini, C-L. Fang, D. Herrington, K. Higgs, R. Rodrigo and N.
Taylor, Aust. J. Chem., 1997, 50, 271.
12 A.P. Kozikowski and C-S. Li, J. Org. Chem., 1987, 52, 3541 and
pertinent references therein.
13 D. P. Curran, J. Am. Chem. Soc., 1983, 105, 5826.
Scheme 3 Reactions and conditions: i, BTIB, THF (path A: 33%, path B:
31%); ii, TsOH, C6H6, 45 °C, 4 h (50%); iii, Cl2CHCHCl2, reflux, 48 h
(65%); iv, p-chloranil, xylenes, reflux, 36 h (60%).
14 R. Carlini, K. Higgs, R. Rodrigo and N. Taylor, Chem. Commun., 1998,
65.
15 Selected data for 7: dH(500 MHz, CDCl3) 1.51 (s, Me), 2.18 (dd, J 17.8,
The nine-step sequence described above is not only the first
3.1, H-1a), 2.67 (m, H-15), 2.74 (dd, J 17.8, 2.3, H-1b), 3.67 (m, H-16),
synthesis of the ring system of viridin, but it also makes 7
4.00 (app dt, J 10.3, 2.6, H-4), 4.06 (dd, J 10.7, 8.1, H-20a), 4.87 (dd,
available in sufficient quantity (19% overall, Scheme 3) to
J 9.8, 8.1, H-20b), 5.74 (app s, H-2, H-3), 7.55 (d, J 8.1, H-11), 7.89 (d,
enable a comprehensive investigation for installation of the
oxygen substituents in ring A, by derivatisation of the C2–C3
alkene, to be undertaken. Dehydrogenation of the dihydrofuran
J 8.1, H-12). Full details will be published later.
Communication 9/05731E
1948
Chem. Commun., 1999, 1947–1948