ORGANIC
LETTERS
2000
Vol. 2, No. 4
511-513
Photolabile Dendrimers Using
o-Nitrobenzyl Ether Linkages
Mario Smet,† Li-Xin Liao, Wim Dehaen,† and Dominic V. McGrath*
Department of Chemistry, The UniVersity of Arizona, Tucson, Arizona 85718
Received December 20, 1999
ABSTRACT
Benzyl aryl ether dendrimers containing photosensitive, veratryl-based o-nitrobenzyl AB linkages (bold bonds) were prepared to the third
generation and shown to undergo site-specific degradation when irradiated with ultraviolet light.
Dendritic macromolecules with a variety of functions have
been prepared by precise synthetic placement of groups
within the structural interior or periphery.1 With several
discrete structural regions within dendritic architecture,
simple incorporation of photolabile linkages into dendrimers
could provide a wide range of materials with many potential
functions including light-assisted drug delivery, polymer-
supported organic synthesis, or other applications where
selective degradation of material is necessary.2
nitrobenzyl ether moiety, well known as a versatile protecting
group in organic synthesis,3 as a readily cleavable linker for
solid-phase synthesis,4 as a masking group for “caged”
biological molecules and prodrugs,5 and as cleavable units
in host-guest6 and materials chemistry.7,8
Racemic secondary alcohol 19 was used to prepare a series
of photolabile dendrimers containing R-substituted-o-ni-
trobenzyl10 linkages. Alkylation of 1 with first-, second-, and
third-generation benzyl aryl ether dendrons in the presence
of K2CO3 in acetone yielded photolabile dendrons 2a-c.
Dendrimers 3a-c were obtained directly from 2a-c and
1,3,5-benzenetricarbonyl chloride as mixtures of two dia-
stereomers (homo- and heterochiral) in racemic form (i.e.,
RRR, SSS, RRS, RSS) in moderate yields (Scheme 1).11 The
In this paper we present the installation of photolabile
linkages proximal to the core unit of benzyl aryl ether
dendrimers. Our approach employs the photolabile o-
† Current address: Department of Chemistry, Katholieke Universiteit
Leuven, BE-3001 Heverlee, Belgium.
(1) (a) Newkome, G. R.; Moorefield, C. N.; Vo¨gtle, F. Dendritic
Molecules. Concepts, Syntheses, PerspectiVes; VCH: Cambridge, 1996. (b)
Zeng, F.; Zimmerman, S. C. Chem. ReV. 1997, 97, 1681-1712. (c) Archut,
A.; Vo¨gtle, F. Chem. Soc. ReV. 1998, 27, 233-240. (d) Matthews, O. A.;
Shipway, A. N.; Stoddart, J. F. Prog. Polym. Sci. 1998, 23, 1-56. (e) Smith,
D. K.; Diederich, F. Chem. Eur. J. 1998, 4, 1353-1361. (f) Fischer, M.;
Vo¨gtle, F. Angew. Chem. 1999, 111, 934-955; Angew. Chem., Intl. Ed.
1999, 38, 885-905.
(2) (a) Enzymatically degradable dendrimers have been prepared and
promoted as possible drug carriers: Seebach, D.; Herrmann, G. F.;
Lengweiler, U. D.; Bachmann, B. M.; Amrein, W. Angew. Chem. 1996,
108, 2969-2972; Angew. Chem., Int. Ed. Engl. 1996, 35, 2795-2797. (b)
Photolabile and thermally labile hyperbranched polyesters have been
reported by Voit, B., et al., at the 13th Biennial Carl S. Marvel Symposium,
Tucson, AZ, March 14-16, 1999.
(3) (a) Kocie′nski, P. J. Protecting Groups; Thieme: New York, 1994.
(b) Green, T. W. ProtectiVe Groups in Organic Synthesis; Wiley: New
York, 1981. (c) Pillai, V. N. R. Synthesis 1980, 1-26.
(4) (a) James, I. W. Tetrahedron 1999, 55, 4855-4946. (b) Osborn, H.
M. I.; Khan, T. H. Tetrahedron 1999, 55, 1807-1850. (c) Blackburn, C.
Biopolymers 1998, 47, 311-351.
(5) For leading references, see: Reinhard, R.; Schmidt, B. F. J. Org.
Chem. 1998, 63, 2434-2441.
(6) (a) Piatniski, E. L.; Deshayes, K. D. Angew. Chem. 1998, 110, 1022-
1024; Angew. Chem., Int. Ed. 1998, 37, 970-972. (b) Grell, E.; Warmuth,
R. Pure Appl. Chem. 1993, 65, 373-379. (c) Warmuth, R.; Grell, E.; Lehn,
J.-M.; Quinkert, G. HelV. Chim. Acta 1991, 74, 671-681.
(7) Folmer, B. J. B.; Cavini, E.; Sijbesma, R. P.; Meijer, E. W. Chem.
Commun. 1998, 1847-1848.
(8) Hong, S. I.; Joo, S. Y.; Kang, D. W. In Desk Reference of Functional
Polymers; Arshady, R., Ed.; American Chemical Society: Washington, DC,
1997; pp 293-310.
(9) Teague, S. J. Tetrahedron Lett. 1996, 37, 5751-5754.
(10) For leading references on R-substituted-o-nitrobenzyl linkages,
see: Holmes, C. P.; Jones, D. G. J. Org. Chem. 1995, 60, 2318-2319.
Holmes, C. P. J. Org. Chem. 1997, 62, 2370-2380.
10.1021/ol991373b CCC: $19.00 © 2000 American Chemical Society
Published on Web 01/29/2000