secondary and the primary monobenzoates 23 and 24 after
hydrolytic work-up, presumably through the 1,3-dioxolenium
intermediate 22. The mixture without separation was then
stirred in CHCl3 containing TsOH to converge to the single
primary monobenzoate 24, which was desilylated to give the
triol 25, mp 208–209, [a]3D0 –70.3 (c 0.92, THF). Benzoylation
of 25 using 1 equiv. of BzCl allowed regioselective monoacyla-
tion at the desired position to give the single dibenzoate 26, mp
254–256 °C, [a]3D1 294.4 (c 0.59, THF), along with a minor
amount of the separable regioisomer. The observed preferential
generation of 26 may be due to the steric hindrance of the
primary benzoate functionality, which shields the exo-hydroxy
functionality considerably. The bromo ether linkage of 26 was
then cleaved reductively to yield the triol 27, mp 169–170 °C,
[a]2D8 –64.5 (c 0.54, CHCl3). As above, on sequential per-O-
silylation, thermolysis and desilylation, 27 afforded the cyclo-
hexene dibenzoate having the structure 2 which was proposed
as (–)-epizeylenol, mp 154–155 °C, [a]2D7 2139.1 (c 0.22,
CHCl3), but its physical and spectroscopic data were not
identical with those reported for the natural product, mp
206–207 °C.4 It was also confirmed that the secondary benzoyl
functionality of 2 was not rearranged during these transforma-
tion reactions as it afforded the corresponding 6-keto derivative,
mp 230–232 °C, [a]2D9 2220.5 (c 0.12, CHCl3). Thus, the
proposed structures of (2)-epizeylenol 2 and (2)-tonkinenin A
4 were both found to be erroneous.
Scheme 2 Reagents and conditions: i, BzCl, pyridine, DMAP (cat.) (90%);
ii, MCPBA, CH2Cl2, room temp. (91%); iii, BF3·OEt2, toluene, –20 °C; iv,
TsOH, CHCl3, ~ 30 °C; v, HF, MeCN, THF, ~ 30 °C (83%, 3 steps); vi,
BzCl (1 equiv.), pyridine, DMAP (cat.) (52%); vii, Zn, NH4Cl, aq. THF,
reflux (77%); viii, TMSCN, DMF, 80 °C; ix, Ph2O, reflux, 25 min; x, HF,
MeCN, ~ 30 °C (76%, 3 steps).
15 with zinc in aqueous THF containing NH4Cl to give the triol
16, mp 166–168 °C, [a]2D9 255.4 (c 0.66, CHCl3), having four
contiguous oxygen functionalities on the cyclohexane moiety.
Having introduced the requisite functionalities, the triol 16
was pertrimethylsilylated using TMSCl13 in DMF to give the
silyl ether 17 which was heated in refluxing Ph2O for 15 min to
give (–)-zeylenol 1, mp 129–130 °C, [a]2D3 2140.5 (c 1.02,
CHCl3) [lit.,3 mp 144–145 °C, [a]D25 2116.3 (c 0.915, CHCl3)],
after desilylation of the crude product.
(+)-Pipoxide 5 was obtained from (–)-zeylenol 1 under
Mitsunobu conditions.14 Thus, on treatment with DEAD and
PPh3 in THF, 1 afforded (+)-pipoxide 5, mp 129 °C, [a]2D8 +55.2
(c 0.78, CHCl3) [lit.,7 mp 152 °C, [a]D23 +53 (c 0.02, CHCl3)],
stereoselectively.
We thank the Takeda Science Foundation for financial
support.
Notes and references
† Satisfactory analytical (combustion and/or high resolution mass) and
spectroscopic (IR, 1H and 13C NMR, MS) data was obtained for isolable
new compounds.
1 A pertinent review, see: V. S. Parmar, O. D. Tyagi, A. Malhotra, S. K.
Singh, K. S. Bisht and R. Jain, Nat. Prod. Rep., 1994, 15, 219.
2 C. Thebtaranonth and Y. Thebtaranonth, Acc. Chem. Res., 1986, 19,
84.
3 S. D. Jolad, J. J. Hoffmann, K. H. Schram, J. R. Cole, M. S. Tempesta
and R. B. Bates, J. Org. Chem., 1981, 46, 4267.
In order to obtain (–)-uvarigranol G 3, which was proposed as
the C-6 epimer of (–)-zeylenol 1, we attempted its synthesis
from 1 by sequential allylic oxidation and stereoselective
reduction. Thus, we first treated 1 with MnO2 in a mixture of
CH2Cl2 and EtOAc to give the enone 19. To our surprise, the
physical and spectroscopic data of the enone 19, mp 158–160
°C, [a]2D7 226.0 (c 0.89, MeOH), obtained quantitatively, were
found to be identical with those of (–)-tonkinenin A, mp
158–159 °C,6 [a]D24 221.6 (c 1.71, MeOH),6 which was
proposed as 4.6 Thus, we were able to accomplish the first
synthesis of this natural product unexpectedly and have revised
its structure as 19. As expected, reduction of 19 with NaBH4/
4 S. D. Jolad, J. J. Hoffmann, J. R. Cole, M. S. Tempesta and R. B. Bates,
Phytochemistry, 1984, 23, 935.
5 X.-P. Pan, R.-Y. Chen and D.-Q. Yu, Phytochemistry, 1998, 47,
1063.
6 W.-M, Zhao, G.-W. Qin, R.-Z. Yang, T.-Y. Jiang. W.-X. Li, L. Scott and
J. K. Snyder, Tetrahedron, 1996, 52, 12 373.
7 G. W. Holbert, B. Ganem, D. V. Engen, J. Clardy, L. Borsub, K.
Chantrapromma, C. Sadavongvivad and Y. Thebtaranonth, Tetrahedron
Lett., 1979, 715.
8 G. R. Schulte and B. Ganem, Tetrahedron Lett., 1982, 23, 4299.
9 K. Ogasawara, Pure Appl. Chem., 1994, 66, 2119.
10 K. Hiroya, Y. Kurihara and K. Ogasawara, Angew. Chem., Int. Ed.
Engl., 1995, 34, 2287.
11 H. Konno and K. Ogasawara, Synthesis, 1999, 1135.
12 K. Hiroya and K. Ogasawara, Chem. Commun., 1998, 2033.
13 K. Mai and G. Patil, J. Org. Chem., 1986, 51, 3545.
14 O. Mitsunobu, Synthesis, 1981, 1; D. L. Hughes, Org. React., 1992, 42,
335; D. L. Hughes, Org. Prep. Proced. Int., 1996, 28, 127.
15 A. L. Gemal and J. L. Luche, J. Am. Chem. Soc., 1981, 103, 5454.
16 M. Prystas. H. Gustafsson and F. Sorm, Collect. Czech. Chem.
Commun., 1971, 36, 1487.
15
CeCl3 allowed diastereoselective reduction of the enone
carbonyl to give (–)-uvarigranol G 3, mp 62–64 °C, [a]2D9 245.8
(c 0.73, CHCl3) [lit.,5: mp 67–69 °C, [a]1D6 244 (c 0.08,
CHCl3)].
To obtain (–)-epizeylenol 2, which was proposed as the C-1
epimer of (–)-zeylenol 1, the primary alcohol 12 was benzoy-
lated to give 20, which was converted into the epoxide 21,
diastereoselectively, from the convex-face (Scheme 2). On
exposure to BF3·OEt216 in toluene, 21 afforded a mixture of the
Communication 9/05631I
2198
Chem. Commun., 1999, 2197–2198