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lowed by oxidation using the SO3–pyridine complex
giving the aldehyde 18 in 95% yield. Olefination of the
aldehyde 18 with stabilized ylide Ph3PꢀCHCO2Et gave
the (E)-a,b-unsaturated ester 19 in 94% yield. The ester
function was transformed into a methyl group to fur-
nish 20 in three steps in 80% overall yield—DIBAL-H
reduction to an allylic alcohol, mesylation, followed by
reduction of the mesylate with lithium triethyl borohy-
dride. Next, desilylation of 20 gave the primary alcohol
21 in 96% yield. The hydroxyl group in 21 was oxidized
to the methyl ester 22 in three steps in 90% yield—oxi-
dation using the SO3–pyridine complex to the aldehyde,
subsequent oxidation of the aldehyde using sodium
chlorite, followed by esterification with CH2N2. Acid
treatment of the ester 22 deprotected the acetonide ring
with concomitant cyclization furnishing the targeted
prelactone 1 in 80% yield.
9. Boddien, C.; Gerber-Nolte, J.; Zeeck, A. Liebigs Ann.
Chem. 1996, 1381–1384.
10. O’Hagen, D. In The Polyketide Metabolites; O’Hagen,
D., Ed.; Ellis Horwood: New York, 1991; pp. 116–137.
11. For earlier syntheses of prelactones see Refs. 12 and 13.
12. Hanefeld, U.; Hooper, A. M.; Staunton, J. Synthesis
1999, 401–403.
13. Esumi, T.; Fukuyama, H.; Oribe, R.; Kawazoe, K.;
Iwabuchi, Y.; Irie, H.; Hatakeyama, S. Tetrahedron Lett.
1997, 38, 4823–4826.
Our synthetic prelactone C showed rotation [h]2D0 +37.8
(c 0.7, MeOH); lit.6 value: [h]2D0 +57.6 (c 0.5, MeOH).
The lower specific rotation of the final product reflects
the moderate enantiomeric excess obtained in the
Sharpless kinetic resolution step (1613), a phe-
nomenon often encountered with trisubstituted epoxy
alcohols.23 Efforts are now underway to standardize the
reaction conditions of the resolution step to improve
the enantioselectivity of the product. The spectroscopic
data of our synthetic product24,25 were identical with
those of the naturally occurring prelactone C.6
14. Chakraborty, T. K.; Dutta, S. J. Chem. Soc., Perkin
Trans. 1 1997, 1257–1259.
15. For earlier works on the application of our method in the
synthesis of natural products, see Refs. 16–18.
16. Chakraborty, T. K.; Dutta, S. Tetrahedron Lett. 1998, 39,
101–104.
17. Chakraborty, T. K.; Das, S. J. Ind. Chem. Soc. 1999,
611–616.
18. Chakraborty, T. K.; Das, S. Chem. Lett. 2000, 80–81.
19. Gao, Y.; Hanson, R. M.; Klunder, J. M.; Ko, S. Y.;
Masamune, H.; Sharpless, K. B. J. Am. Chem. Soc. 1987,
109, 5765–5780.
20. The minor isomer could be separated more easily after
the debenzylation step.
In conclusion, the synthesis demonstrates the practical
utility of the radical-mediated opening of trisubstituted
epoxy alcohols to construct an important structural
moiety consisting of 2-methyl-1,3-diol framework that
appears in various propionate-derived polyketides. The
methodology can be successfully employed in the syn-
thesis of many natural products.
21. Rychnovsky, S. D.; Rogers, B. N.; Richardson, T. I. Acc.
Chem. Res. 1998, 31, 9–17.
22. Evans, D. A.; Rieger, D. L.; Gage, J. R. Tetrahedron
Lett. 1990, 31, 7099–7102.
Acknowledgements
23. Katsuki, T.; Martin, V. S. Org. React. 1996, 48, 1–299.
24. All new compounds were characterized by IR, 1H and
13C NMR and mass spectroscopic studies.
25. Selected physical data of 1. Rf=0.5 (silica, 70% EtOAc in
petroleum ether); [h]2D0 +37.8 (c 0.7, MeOH); IR (neat):
The authors wish to thank Drs. A. C. Kunwar and M.
Vairamani for NMR and mass spectroscopic assistance,
respectively; CSIR, New Delhi for research fellowship
(S.T.) and Young Scientist Award Research Grant
(T.K.C.).
1
wmax 3400, 2925, 1730, 1225 cm−1; H NMR (400 MHz,
CDCl3): l 5.79 (ddq, J=15.2, 6.6, 1 Hz, 1H, C7-H), 5.43
(ddq, J=15.2, 8.2, 2 Hz, 1H, C6-H), 4.17 (dd, J=10.4,
8.2 Hz, 1H, C5-H), 3.74 (ddd, J=8, 7, 5.8 Hz, 1H,
C3-H), 3.07 (br s, 1H, OH), 2.87 (dd, J=17, 5.8 Hz, 1H,
C2-H), 2.46 (dd, J=17, 8 Hz, 1H, C2-H%), 1.77 (dd,
J=6.6, 2 Hz, 3H, C8-H3), 1.64 (ddq, J=10.4, 7, 6.8 Hz,
1H, C4-H), 1.02 (d, J=6.8 Hz, 3H, C4-CH3); 13C NMR
(125 MHz, CDCl3): l 170.34, 132.41, 127.61, 84.11,
69.53, 41.49, 39.08, 17.62, 13.66; MS (EI): m/z 153 [M++
H−H2O].
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