P. Schell et al. / Tetrahedron Letters 42 (2001) 3811–3814
3813
MeO2C
R1O
R2O
MeO2C
a
O
R1O
O
R1O
R2O
MeO2C
O
+
R2O
29: R1 = R2 = H
29: R1 = R2 = H
30: R1 = R2 = H
3: R1 = H, R2 = Bn
15: R1 = PMB, R2 = Bn
3: R1 = H, R2 = Bn
15: R1 = PMB, R2 = Bn
31: R1 = H, R2 = Bn
32: R1 = PMB, R2 = Bn
Scheme 5. (a) NaOMe, MeOH, rt, 80%.
Scheme 6. (a) TBSCl, imidazole, CH2Cl2, 85%; (b) Ac2O, pyridine, 86%; (c) i. DMDO, acetone, 0°C, ii. 4-pentenol, ZnCl2,
CH2Cl2, 25–30%.
Thiem7 prompted us to investigate if
glycals could serve as key intermediates for the prepara-
tion of -iduronic acid building blocks. Exploitation of
D-glucuronic acid
Acknowledgements
L
This work was supported by grants from the National
Institutes of Health (1RO1HL64799). Financial support
from the DAAD (German Academic Exchange Service)
for a postdoctoral fellowship for P.S. and FOMEC for
a postdoctoral fellowship for H.A.O. is gratefully
acknowledged. Funding for the MIT-DCIF Inova 501
was provided by NSF (Award c CHE-9808061) and
for an INOVA 501 by NSF (DBI-9729592).
such an epimerization strategy would allow ready
access to these otherwise cumbersome to prepare differ-
entially protected synthons. Treatment of protected gly-
cals 3 and 15 with concentrated solutions of sodium
methoxide7 resulted in complete degradation of the
starting glycals. Lower concentrations of base and
shorter reaction times resulted in 1:1 mixtures of 3/31
and 15/32, respectively (80% yield in both cases,
Scheme 5). Silica column chromatography readily facil-
itated the separation of the mixtures to provide pure
References
L
-iduronic acid glycals 31 and 32.
1. Bernfield, M.; Gotte, M.; Park, P. W.; Reizes, O.;
Fitzgerald, M. L.; Lincecum, J.; Zako, M. Annu. Rev.
Biochem. 1999, 86, 729–777.
In order to access differentially protected
L-iduronic
acid building blocks, the conversion of -iduronic acid
L
glycals 32 and 33 to n-pentenyl glycosides was investi-
gated. Transformation of 32 and 33 into the corre-
sponding n-pentenyl glycosides under the conditions for
2. van Boeckel, C. A. A.; Petitou, M. Angew. Chem., Int.
Ed. Engl. 1993, 12, 1671–1690.
3. (a) Lubineau, A.; Gavard, O.; Alais, J.; Bonnaffe, D.
Tetrahedron Lett. 2000, 41, 307–311; (b) Ojeda, R.; de
Paz, J. L.; Martin-Lomas, M.; Lassaletta, J. M. Synlett
1999, 8, 1316–1318; (c) Hinou, H.; Kurosawa, H.; Mat-
suoka, K.; Terunuma, D.; Kuzuhara, H. Tetrahedron
Lett. 1999, 40, 1501–1504; (d) Rochepeau-Jobron, L.;
Jacquinet, J.-C. Carbohydr. Res. 1997, 303, 395–406 and
references cited therein; (e) Medakovic, D. Carbohydr.
Res. 1994, 253, 299–300 and references cited therein; (f)
Jacquinet, J.-C.; Petitou, M.; Duchaussoy, P.; Lederman,
I.; Choay, J.; Torri, G.; Sinay, P. Carbohydr. Res. 1984,
130, 221–241; (g) Czuk, R.; Hoenig, H.; Nimpf, J.; Weid-
mann, H. Tetrahedron Lett. 1980, 21, 2135–2136.
4. Seeberger, P. H.; Bilodeau, M. T.; Danishefsky, S. J.
Aldrichim. Acta 1997, 30, 75–92.
D
-glucuronic acid glycals resulted in a mixture of the
desired -iduronic acid glycosides (34 and 36) and
-glucuronic acid derivatives (35 and 37) with a prefer-
ence for the latter. Reaction of 4-O-acetate protected
glycal 38 furnished preferentially -iduronic acid n-pen-
L
L
L
tenyl glycoside 39. The steric and electronic features of
the O-4 protecting group strongly influence the confor-
mation of the glycals and thus reactions involving such
species. The epoxides derived from
cals are less stable than those derived from
curonic acid glycals leading to lower yields and
anomeric mixtures in the preparation of n-pentenyl
glycosides (Scheme 6).
L
-iduronic acid gly-
-glu-
D
In summary, we have disclosed different synthetic
routes to differentially protected
5. Gordon, D. M.; Danishefsky, S. J. Carbohydr. Res. 1990,
206, 361–366.
D-glucuronic acid gly-
cals that may serve as intermediates en route to a
variety of natural products. The conversion of these
glycals into thioethyl and n-pentenyl glycoside donors
has also been demonstrated.
6. Ichikawa, S.; Shuto, S.; Matsuda, A. J. Am. Chem. Soc.
1999, 121, 10270–10280.
7. Thiem, J.; Ossowski, P. J. Carbohydr. Chem. 1984, 3,
287–313.