LETTER
Preparation of Enantiopure Secosyrins 1 and 2
3341
25
20
[a]D +40.0 (c 1.0, CHCl3), lit.7a [a]D +40.2 (c 1.1,
OTBDPS
OR
OR
OTBDPS
O
OTBDPS
O
CHCl3), for 2b: [a]D +42.5 (c 0.5, CHCl3), lit.7a [a]D
+42.3 (c 0.5, CHCl3)}.
25
20
OH
HO
i
ii
O
O
In conclusion, we present herein an alternative and effi-
cient approach for the preparation of enantiopure seco-
syrins 1 and 2. This synthetic scheme uses a readily
available D-arabinose derivative as the starting material, it
involves ten easily executed steps and delivers the target-
ed natural products in overall yields higher than 20% for
both.19 Moreover, the stereoselective construction of the
1,7-dioxaspiro[4.4]nonane framework through the HWE–
IHMA strategy could be proved significantly versatile for
the synthesis of analogous systems.
BnO
BnO
OH
BnO
6 R = H
4
5
iii
7 R,R = CMe2
iv
O
O
OH
OR
H
O
O
O
O
vi
MeO2C
+
O
O
O
BnO
BnO
BnO
10
11
8 R = TBDPS
9 R = H
19:1
v
vii
References and Notes
O
O
O
O
(1) Wong, H. N. C. Eur. J. Org. Chem. 1999, 1757.
(2) (a) Smith, M. J.; Mazzola, E. P.; Sims, J. J.; Midland, S. L.;
Keen, N. T.; Burton, V.; Stayton, M. M. Tetrahedron Lett.
1993, 34, 223. (b) Midland, S. L.; Keen, N. T.; Sims, J. J.;
Midland, M. M.; Stayton, M. M.; Burton, V.; Smith, M. J.;
Mazzola, E. P.; Graham, K. J.; Clardy, J. J. Org. Chem.
1993, 58, 2940.
O
O
viii
O
O
OH
OH
+
BnO
13
OH
BnO
OH
BnO
12
14
ix
(3) (a) Keen, N. T.; Tamaki, S.; Kobayashi, D.; Gerhold, D.;
Stayton, M. M.; Shen, H.; Gold, S.; Lorang, J.; Thordal-
Christensen, H.; Dahlbeck, D.; Staskawicz, B. Mol. Plant
Microbe Interact. 1990, 3, 112. (b) Keen, N. T.; Buzzell, R.
I. Theoret. Appl. Genet. 1991, 81, 133.
O
O
x
2a
2b
O
HO
OH
(4) Midland, S. L.; Keen, N. T.; Sims, J. J. J. Org. Chem. 1995,
60, 1118.
15
(5) Selected publications: (a) Atkinson, M. M.; Midland, S. L.;
Sims, J. J.; Keen, N. T. Plant Physiol. 1996, 112, 297.
(b) Tsurushima, T.; Midland, S. L.; Zeng, C.-M.; Ji, C.;
Sims, J. J.; Keen, N. T. Phytochemistry 1996, 43, 1219.
(c) Ji, C.; Okinaka, Y.; Takeuchi, Y.; Tsurushima, T.;
Buzzell, R. I.; Sims, J. J.; Midland, S. L.; Slaymaker, D.;
Yoshikawa, M.; Yamaoka, N.; Keen, N. T. Plant Cell 1997,
9, 1425. (d) Ji, C.; Boyd, C.; Slaymaker, D.; Okinaka, Y.;
Takeuchi, Y.; Midland, S. L.; Sims, J. J.; Herman, E.; Keen,
N. T. Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 3306.
(e) Tsurushima, T.; Ji, C.; Okinaka, Y.; Takeuchi, Y.; Sims,
J. J.; Midland, S. L.; Yoshikawa, M.; Yamaoka, N.; Keen, N.
T. Dev. Plant Pathol. 1998, 13, 139. (f) Slaymaker, D. H.;
Keen, N. T. Plant Sci. 2004, 166, 387.
(6) (a) Kuwahara, S.; Moriguchi, M.; Miyagawa, K.; Konno,
M.; Kodama, O. Tetrahedron Lett. 1995, 36, 3201.
(b) Kuwahara, S.; Moriguchi, M.; Miyagawa, K.; Konno,
M.; Kodama, O. Tetrahedron 1995, 51, 8809. (c) Wood, J.
L.; Jeong, S.; Salcedo, A.; Jenkins, J. J. Org. Chem. 1995,
60, 286. (d) Honda, T.; Mizutani, H.; Kanai, K. J. Org.
Chem. 1996, 61, 9374. (e) Henschke, J. P.; Rickards, R. W.
Tetrahedron Lett. 1996, 37, 3557. (f) Ishihara, J.; Sugimoto,
T.; Murai, A. Synlett 1996, 335. (g) Zeng, C.-M.; Midland,
S. L.; Keen, N. T.; Sims, J. J. J. Org. Chem. 1997, 62, 4780.
(h) Yoda, H.; Kawauchi, M.; Takabe, K.; Ken, H.
Heterocycles 1997, 45, 1895. (i) Ishihara, J.; Sugimoto, T.;
Murai, A. Tetrahedron 1997, 53, 16029. (j) Yu, P.; Wang,
Q.-G.; Mak, T. C. W.; Wong, H. N. C. Tetrahedron 1998,
54, 1783. (k) Di Florio, R.; Rizzacasa, M. A. Austr. J. Chem.
2000, 53, 327. (l) Chenevert, R.; Dasser, M. Can. J. Chem.
2000, 78, 275. (m) Chenevert, R.; Dasser, M. J. Org. Chem.
2000, 65, 4529.
Scheme 1 Reagents and conditions: i) 90% TFA in H2O, CH2Cl2,
0 °C, 87%; ii) NaBH4, MeOH, 0 °C to r.t., 99%; iii) MeC(OMe)2Me,
acetone, PTSA, r.t., 92%; iv) CrO3, pyridine, Ac2O, r.t., 98%; v)
TBAF, AcOH, THF, 0 °C, 85%; vi) (MeO)2P(O)CH2CO2Me, n-BuLi,
THF, –50 °C to 0 °C, 10: 77%, 11: 4%; vii) PTSA, MeOH, 0 °C, 95%;
viii) Et3N, CHCl3, 0 °C, 13: 14%, 14: 63%; ix) H2, Pd/C, r.t., 99%; x)
[Me(CH2)4CO]2O (for 2a) or [Me(CH2)6CO]2O (for 2b), DMAP,
THF, 0 °C to r.t., 2a: 72%, 2b: 76%.
Practically, a number of different conditions (bases, sol-
vents and temperatures) were employed to check not only
the feasibility of this ring-closure but its stereoselective
outcome as well. However, the best results were obtained
using the conditions previously reported,7a giving in pref-
erence the spiro-tetrahydrofuran system 14 along with its
diastereoisomer 13 (in a ratio of ca. 4.5:1).14b It seems that
the role of the neighboring protective group (TBS or Bn)
is not crucial for the diastereoselectivity of this reaction.
Stereochemistry of the newly formed quaternary center
was assigned comparing the spectra data of easily separa-
ble 13 and 14 with those obtained for the analogous cy-
clized intermediates.7a However, it was indisputably
assured when 14 was hydrogenolyzed to give diol 1517
{for 15: [a]D25 +75.0 (c 0.2, MeOH), lit.7c [a]D25 +75.3 (c
0.22, MeOH)}. Finally, 15 was regioselectively acylated7c
with hexanoic or octanoic anhydride to afford secosyrin
1 (2a) and secosyrin 2 (2b), respectively18 {for 2a:
Synlett 2006, No. 19, 3340–3342 © Thieme Stuttgart · New York