C. Bonini et al. / Tetrahedron: Asymmetry 9 (1998) 2559–2561
2561
Scheme 2.
References
1. O’Hagan, D. Nat. Prod. Rep. 1995, 12, 1 and references cited therein.
2. Dutton, C. J.; Banks, B. J.; Cooper, C. B. Nat. Prod. Rep. 1995, 12, 165 and references cited therein.
3. See: (a) Heathcock, C. H. In Comprehensive Organic Synthesis, Trost, B. M., Fleming, I., Heathcock, C. H., Eds; Pergamon
Press: Oxford, 1991; Vol. 2, pp. 181–238. (b) Kim, M.; Williams, S. F.; Masamune, S. In Comprehensive Organic
Synthesis, Trost, B. M., Fleming, I., Heathcock, C. H., Eds; Pergamon Press: Oxford, 1991; Vol. 2, pp. 239–275. (c)
Paterson, I. Pure Appl. Chem. 1992, 64, 1821.
4. Nicholas, G. In Comprehensive Organic Synthesis, Trost, B. M., Fleming, I., Heathcock, C. H., Eds; Pergamon Press:
Oxford, 1991; Vol. 8, pp. 1–24.
5. Domon, L.; Vogeleisen, F.; Uguen, D. Tetrahedron Lett. 1996, 37, 2773.
6. Chenevert, R.; Courchesne, G. Tetrahedron: Asymmetry 1995, 6, 2093.
7. (a) Bonini, C.; Racioppi, R.; Righi, G.; Viggiani, L. J. Org. Chem. 1993, 58, 802. (b) Bonini, C.; Racioppi, R.; Righi, G.;
Rossi, L.; Viggiani, L. Tetrahedron: Asymmetry 1993, 4, 793.
8. Bonini, C.; Giugliano, A.; Racioppi, R.; Righi, G. Tetrahedron Lett. 1996, 37, 2487.
1
9. The relative stereochemistry of compounds 6a and b was later confirmed by H-NMR analysis of compound 7 which
possesses a relative syn–syn configuration: in fact the coupling constant of the protons on C-3 and C-5 with the proton
on C-4 (on the methyl group) shows the typical value of 2 Hz, which is the usual for the axial–equatorial coupling (the
corresponding axial–axial coupling for the other anti–anti stereoisomer would resonate at the value of 8–10 Hz). The
relative configuration of the two hydroxyl groups has been easily assigned by the Rychnovsky method (Rychnovsky, S.
D.; Skalitzky, D. J. Tetrahedron Lett. 1990, 31, 7) with 13C-NMR analysis of the corresponding acetonide derivatives.
10. PPL (Porcine Pancreatic Lipase) and PFL (Pseudomonas fluorescens Lipase) are commercially available from FLUKA.
11. Both the reactions were carried out, on a gram scale, in diethyl ether with a 0.06 M concentration of substrate, 0.6 M of
vinylacetate and 30 U/mg of enzyme.
12. The reaction was carried out in phosphate buffer 0.2 M at pH=7 in 2 h.
13. The ee for compounds 10 and 11 were determined by 1H-NMR (CDCl3) analysis with (−)-Eu(hfc)3 at different
concentrations, which shows clear differentiation of the CH3 signals of the isopropylidene ring.
14. Compounds 10 and 11: 1H-NMR (CDCl3): 0.91 (3H, d, J=7.03 Hz), 1.38 (3H, s), 1.3–1.4 (1H, m), 1.45 (3H, s), 1.62 (1H,
s), 1.8–2.0 (4H, m), 2.06 (3H, s), 2.3 (1H, bs), 3.77 (2H, m), 4.04 (1H, m), 4.1–4.2 (2H, m) ppm; 13C-NMR (CDCl3): 5.14,
19.70, 20.82, 29.96, 32.27, 35.38, 35.62, 61.36, 70.09, 73.07, 99.14, 170.89 ppm. Compound 10 (from PPL): [α]D=+14.4
(c 0.9, CHCl3). Compound 11 (from PFL): [α]D=−15.5 (c 0.9, CHCl3).
15. All new compounds exhibited satisfactory spectroscopic exact mass data.
16. The syn–syn prepared subunits can be found, i.e. in calyculin, a potent inhibitor of protein phosphonate (for structure and
synthesis see Hamada, Y.; Yokokawa, F.; Kabeya, M.; Hatano, K.; Kurono, Y.; Shioiri, T. Tetrahedron 1996, 52, 8297, and
references cited therein); in the immunosuppressant (−)-FK-506 (see for structure Tanaka, H.; Kuroda, A.; Marusawa, H.;
Hatanaka, H.; Kino, T.; Goto, T.; Hashimoto, M.; Taga, T. J. Am. Chem. Soc. 1987, 111, 1157); and in conagenin, a new
immunomodulator (Hatakeyama, S.; Fukuyama, H.; Mukugi, Y.; Irie, H. Tetrahedron Lett. 1996, 37, 4047).