K. Takabe et al. / Tetrahedron: Asymmetry 15 (2004) 909–912
911
O
Cl
PhSO2
18
9
OH
O
SO2Ph
a
b
OAc
OTBS
OTBS
19
PhS
PhSO2
15a
8a
O
O
O
O
d
c
OH
OMe
20
5
O
O
O
e
Variabilin 1
OH
Scheme 2. Reagents and conditions: (a) 1, MsCl, pyridine; 2, LiAlH4, ether, 0 °C; 94% (two steps); 3, TBSCl, imidazole, DMF; 97%; 4, m-CPBA.
CH2Cl2, 84%; (b) BuLi, HMPA, 5, 0 °C, 84%; (c) 1, Na, THF–2-propanol, (2:3), 76%; 2, concd HCl, MeOH, 94%; (d) 1, TPAP (tetrapropyl-
ammonium perruthenate), NMO, CH2Cl2, 68%; 2, LDA, methyl tetronate, THF, )78 °C; 3, MsCl, pyridine, 0 °C, 73% (two steps); (e) PrSLi, HMPA,
0 °C, 83%.
asymmetric esterification of 10 smoothly brought about
the desired compounds 15 in both high chemical and
high enantiomeric excesses (up to 98% ee), respectively.
References and notes
1. Faulkner, D. J. Tetrahedron Lett. 1973, 14, 3821–3822.
2. Barrow, C. J.; Blunt, J. W.; Munro, M. H. G.; Perry, N. B.
J. Nat. Prod. 1988, 51, 275–281.
3. Cimino, G.; Stefano, S. D.; Minale, L.; Fattorusso, E.
Tetrahedron 1972, 28, 333–341.
We further focused our research on the synthesis of
(18S)-variabilin 1 in light of the above outcome as
shown in Scheme 2. Initially, the mono-acetate 15a was
converted into the silyl ether 8a through a three-step
sequence, which was in turn coupled with the furanyl
side chain 9 prepared from the sulfone 18 under the
similar conditions indicated in Scheme 1, leading to the
silyl sulfone 19 in satisfactory yield. This was then
4. Cafieri, F.; Fattorusso, E.; Santacroce, C.; Minale, L.
Tetrahedron 1972, 28, 1579–1583.
5. (a) Manes, L. V.; Crews, P. J. Nat. Prod. 1986, 49, 787–
793; (b) Barrow, C. J.; Blunt, J. W.; Munro, M. H. G.;
Perry, N. B. J. Nat. Prod. 1988, 51, 1294–1298; (c) Barrow,
C. J.; Blunt, J. W.; Munro, M. H. G. J. Nat. Prod. 1989,
52, 346–359; (d) Liokas, V.; Garson, M. J.; Carver, J. A.
submitted to desulfonylation and deprotection to pro-
21
D
vide 5, ½aꢀ )5.5 (c 0.91, CHCl3),8;10 the chiral segment
ꢀ
Aust. J. Chem. 1989, 42, 1805–1811; (e) Garcıa, M. O.;
Rodrıguez, A. D. Tetrahedron 1990, 46, 1119–1124; (f)
ꢀ
of 1 in 72% (two steps) yield. Finally, a coupling reac-
tion of 5 after TPAP-induced oxidation12 to the alde-
hyde intermediate was effected with methyl tetronate in
the presence of LDA at low temperature followed by the
subsequent dehydroxylation under basic conditions and
demethylation to complete the first asymmetric synthesis
of desired (18S)-1 accompanied with its (20E)-isomer
Kernan, M. R.; Cambie, R. C. J. Nat. Prod. 1991, 54, 265–
268; (g) Ishibashi, M.; Kurosaki, M.; Mikami, Y.;
Kobayashi, J. Nat. Prod. Lett. 1993, 3, 189–192; (h)
Capon, R. J.; Dargaville, T. R.; Davis, R. Nat. Prod. Lett.
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€
€
Holler, U.; Konig, G. M.; Wright, A. D. J. Nat. Prod.
1997, 60, 832–835; (k) Martinez, A.; Duque, C.; Sato, N.;
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Mcphail, K.; D-.Coleman, M. T.; Coetzee, P. J. Nat. Prod.
1998, 61, 961–964; (m) de Epifanio, R. A.; Gabriel, R.;
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(Z/E ¼ 2.8:1, determined by 1H NMR) as a colorless oil,
21
½aꢀ )37.4 (c 0.77, CHCl3).13
D
€
2254; (n) Kehraus, S.; Konig, G. M.; Wright, A. D. J. Nat.
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3. Conclusion
6. It was not until the isolation of (18R)-1 with stereochem-
istry different to the previously reported structure was
accomplished in 1995 by Fujimoto et al.5i from a Carri-
bean sponge, Ircinia felix, that the occurrence of both
stereoisomers of 1 was demonstrated.
7. Takabe, K.; Mase, N.; Hashimoto, H.; Tsuchiya, A.;
Ohbayashi, T.; Yoda, H. Bioorg. Med. Chem. Lett. 2003,
13, 1967–1969.
In summary, this work constitutes the first synthesis of
the naturally occurring furanosesterterpene, (18S)-vari-
abilin, through lipase-catalyzed asymmetric desymmet-
rization of the 1,3-propanediol derivatives and will be
widely applicable to the synthesis of other terpeniod
natural products.
8. For recent examples of lipase-catalyzed desymmetrization
of 1,3-propanediol derivatives, see: (a) Danieli, B.; Lesma,
G.; Macecchini, S.; Passarella, D.; Silvani, A. Tetrahedron:
Asymmetry 1999, 10, 4057–4064; (b) Yokomatsu, T.; Sato,
M.; Shibuya, S. Tetrahedron: Asymmetry 1996, 7, 2743–
2754; (c) Barnett, C. J.; Wilson, T. M.; Wendel, S. R.;
Winningham, M. J.; Deeter, J. B. J. Org. Chem. 1994, 59,
7038–7045, and references cited therein; (d) Guanti, G.;
Banfi, L.; Riva, R. Tetrahedron: Asymmetry 1994, 5, 9–12;
(e) Barnett, C. J.; Wilson, T. M. Tetrahedron Lett. 1989,
Acknowledgements
We are grateful to Amano Pharmaceutical Co., Ltd. and
Meito Sangyo Co., Ltd. for a geneous gift of some
enzymes.