ORGANIC
LETTERS
2
012
Vol. 14, No. 6
612–1615
First Per-6-O-tritylation of Cyclodextrins
†
Ping Zhang, Aixia Wang, Lina Cui, and Chang-Chun Ling*
1
Alberta Glycomics Centre and Department of Chemistry, University of Calgary, 2500,
University Drive NW, Calgary, Alberta T2N 1N4, Canada
Received February 14, 2012
ABSTRACT
Because of the large dimension of the trityl group and the truncated conical geometry of cyclodextrin (CD) molecules, it is unclear if there is
enough space at the narrower end of CDs to permit a per-6-O-tritylation. This work demonstrates that it is indeed possible to simultaneously install
a trityl group at the O6-position of every glucopyranosyl unit in a CD. A novel per-6-substitution method has been developed for CD chemistry.
Triphenylmethyl, or the trityl group, is a common and
important protecting group for alcohols and other func-
1
tional groups. In carbohydrate chemistry, the trityl
group’s large size and superior stability toward bases have
been extensively exploited to achieve regioselectivity in
protecting primary alcohols in the presence of more hin-
dered secondary and tertiary alcohols. In the history of
cyclodextrin (CD) chemistry, the 6-O-tritylation has been
2
,3
studied by several groups since 1969. Recently, Matt
and co-workers have designed another even bulkier
4
version of the trityl group called “super trityl” along with
some capped tritylating reagents for the O6-protection of
2e,f,4a
di-,
5
CDs. To date, a number of 6-O-mono-,
2bꢀd
Figure 1. CPK model of the trityl group in a propeller confor-
mation and a surface model to illustrate the primary rims (front)
of CDs.
(
1) Wuts, P. G. M.; Greene, T. M. Greene’s Protective Groups in
Organic Synthesis, 4th ed.; Wiley-Interscience: Hoboken, NJ, 2007.
2) (a) Cramer, F.; Mackensen, G.; Sensse, K. Chem. Ber. 1969, 102,
(
494–508. (b) Melton, L. D.; Slessor, K. N. Carbohydr. Res. 1971, 18, 29–
37. (c) Boger, J.; Brenner, D. G.; Knowles, J. R. J. Am. Chem. Soc. 1979,
101, 7630–7631. (d) Cottaz, S.; Driguez, H. Synthesis 1989, 755–758. (e)
2c,3a
tri-,
3,4b
and tetratritylated
CD derivatives have been
reported; these tritylated products have played a crucial
role in accessing different multisubstituted CD scaffolds
6
for various applications. Interestingly, despite a long
history of performing 6-O-tritylations, functionalizations
Tanimoto, T.; Tanaka, M.; Yuno, T.; Koizumi, K. Carbohydr. Res.
992, 223, 1–10. (f) Tanimoto, T.; Ikuta, A.; Koizumi, K.; Kimata, K.
J. Chromatogr., A 1998, 825, 195–199.
3) (a) Ling, C.-C.; Coleman, A. W.; Miocque, M. Carbohydr. Res.
1
(
1
2
992, 223, 287–291. (b) Ward, S.; Zhang, P.; Ling, C.-C. Carbohydr. Res.
009, 344, 808–814.
(
4) (a) Armspach, D.; Matt, D. Carbohydr. Res. 1998, 310, 129–133.
b) Poorters, L.; Armspach, D.; Matt, D. Eur. J. Org. Chem. 2003, 8,
377–1381.
5) (a) Armspach, D.; Poorters, L.; Matt, D.; Benmerad, B.;
(6) (a) Boger, J.; Knowles, J. R. J. Am. Chem. Soc. 1979, 101, 7631–
7633. (b) Coleman, A. W.; Ling, C.-C.; Miocque, M. Angew. Chem., Int.
Ed. 1992, 31, 1381–1383. (c) Coleman, A. W.; Ling, C.-C.; Miocque, M.
J. Coord. Chem. 1992, 26, 137–141. (d) Tanimoto, T.; Sakaki, T.;
Koizumi, K. Carbohydr. Res. 1995, 267, 27–38. (e) Armspach, D.; Matt,
D. Chem. Commun. 1999, 1073–1074. (f) Kreji, L.; Budinsky, M.; Kraus,
T.; Cisaova, I. Chem. Commun. 2009, 24, 3557–3559.
(
1
(
Balegroune, F.; Toupet, L. Org. Biomol. Chem. 2005, 3, 2588–2592. (b)
Gramage-Doria, R.; Rodriguez-Lucena, D.; Armspach, D.; Egloff, C.;
Jouffroy, M.; Matt, D.; Toupet, L. Chem.;Eur. J. 2011, 17, 3911–3921.
1
0.1021/ol300358u r 2012 American Chemical Society
Published on Web 03/06/2012