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38, 8053; M. Inoue, M. Sasaki and K. Tachibana, Angew. Chem., Int.
Ed., 1998, 37, 965; M. Sasaki, T. Noguchi and K. Tachibana,
Tetrahedron Lett., 1999, 40, 1337.
3 T. Oishi, Y. Nagumo and M. Hirama, Chem. Commun., 1998, 1041.
4 C. H. Marzabadi and C. D. Spilling, J. Org. Chem., 1993, 58, 3761.
5 P. Schwab. R. H. Grubbs and J. W. Ziller, J. Am. Chem. Soc., 1996, 118,
100.
6 M. Delgago and J. D. Martín, Tetrahedron Lett., 1997, 38, 6299.
7 R. Johansson and B. Samuelsson, J. Chem. Soc., Chem. Commun., 1984,
201.
8 I. Kadota, A. Ohno, Y. Matsukawa and Y. Yamamoto, Tetrahedron
Lett., 1998, 39, 6373.
9 We found that reduction of the ketal rather than the corresponding
hemiacetal using Et3SiH and BF3·OEt2 gave a remarkably higher yield
of the reduction product; 0–70% yield in the case of hemiacetal under
the same reduction conditions. Also see ref. 3.
10 D. L. Lewis, J. K. Cha and Y. Kishi, J. Am. Chem. Soc., 1982, 104,
4976.
11 The stereochemistry of 2 was unambiguously determined by 1H NMR
analysis. Selected data for 2: dH (500 MHz, CDCl3) 0.98 (9H, s,
TBDPS), 0.99 (9H, s, TBDPS), 1.55 (1H, q, J 11.4, H14ax), 1.53–1.60
(1H, m, H22), 1.62–1.69 (1H, m, H22A), 1.71–1.78 (1H, m, H21),
2.05–2.14 (1H, m, H21A), 2.29 (1H, dt, J 11.4, 4.1, H14eq), 2.31-2.38
(1H, m, H8), 2.64 (1H, ddd, J 16.0, 7.7, 3.5, H8A), 3.08–3.15 (2H, m,
H12, H13), 3.28(0) (1H, ddd, J 8.4, 7.7, 3.8, H9), 3.28(5) (1H, ddd, J
11.4, 8.9, 4.1, H15), 3.31–3.40 (2H, m, H20, H24), 3.35 (1H, dd, J 9.0,
8.4, H10), 3.48 (1H, t, J 9.0, H11), 3.62–3.70 (3H, m, H23, H25, H25A),
3.88 (1H, dq, J 8.9, 2.3, H16), 4.01 (1H, dq, J 16.0, 2.8, H5), 4.12 (1H,
dq, J 9.0, 2.3, H19), 4.29 (1H, dd, J 16.0, 5.7, H5A), 4.83 (1H, d, J 11.5,
CH2Ph), 4.89 (1H, d, J 11.5, CH2Ph), 5.64 (1H, dt, J 13.0, 2.3, H18),
5.77 (1H, dddd, J 11.8, 5.1, 3.5, 2.8, H7), 5.83 (1H, dt, J 13.0, 2.3, H17),
5.87 (1H, ddt, J 11.8, 5.7, 2.8, H6), 7.23–7.43 (17H, m, Ph), 7.52–7.56
(4H, m, Ph), 7.59–7.66 (4H, m, Ph).
reaction, the ratio became 1: 1. Although further attempts to
improve the diastereoselectivity and to epimerize 13 were
unsuccessful at this stage, we found that the epimerization could
be obtained at a later stage (vide infra). Acidic methanolysis of
the acetonide 12 followed by protection of the resulting 1,3-diol
as TBDPS ethers gave 14. Removal of the p-methoxybenzyl
group using DDQ followed by treatment with CSA in toluene at
80 °C gave the d-lactone 15. The epimeric lactone 16 was also
synthesized from 13 in an analogous manner. This lactone was
found to undergo epimerization by treatment with imidazole in
toluene under reflux to give a separable 1: 1 mixture of 15 and
16 in 80% yield, while stronger bases such as ButOK and DBU
caused only decomposition. Thus, the undesired epimer 13 was
successfully converted into 15. Treatment of the lactone 15 with
CH2NCHMgBr followed by conversion of the resultant hemi-
acetal to the corresponding methyl acetal afforded 17 as a 1: 1
mixture of anomers. Reduction of the anomeric mixture 179
10
with Et3SiH in the presence of BF3·OEt2 gave 3 as a single
isomer in 96% yield. Finally RCM reaction of 3 with Grubbs’
catalyst 9 at 40 °C in CH2Cl2 gave the ABCDE ring 2 in 93%
yield.11
In conclusion, we have demonstrated that the alkylation–
metathesis strategy is versatile for the convergent synthesis of
the pentacyclic segment 2 of 1. Further studies directed toward
the total synthesis of 1 are currently in progress in our
laboratory.
Notes and references
1 M. Murata, A. M. Legrand, Y. Ishibashi, M. Fukui and T. Yasumoto,
J. Am. Chem. Soc., 1990, 112, 4380; M. Satake, A. Morohashi, H.
Oguri, T. Oishi, M. Hirama, N. Harada and T. Yasumoto, J. Am. Chem.
Soc., 1997, 119, 11325.
2 For recent synthetic studies, see: T. Oishi, M. Shoji, K. Maeda, N.
Kumahara and M. Hirama, Synlett, 1996, 1165; T. Oishi, K. Maeda and
M. Hirama, Chem. Commun., 1997, 1289; T. Oishi, M. Shoji, N.
Kumahara and M. Hirama, Chem. Lett., 1997, 845; T. Oishi, Y. Nagumo
and M. Hirama, Synlett, 1997, 307; S. Hosokawa and M. Isobe, Synlett,
1996, 351; T. Oka, K. Fujiwara and A. Murai, Tetrahedron, 1996, 37,
Communication 9/03063H
1064
Chem. Commun., 1999, 1063–1064