5-(3-Iodopropoxy)-2-nitrobenzyl alcohol

[185994-27-8]  · C10H12INO4  · (MW 337.11)

(reagent used as a photolabile linker for solid-phase synthesis)

Physical Data: mp 57-59 °C.

Solubility: CH2Cl2, most organic solvents.

Form Supplied in: yellow powder.

Handling, Storage, and Precautions: prevent excess exposure to light and store at 4 °C.

Preparation of Linker

The linker 5-(3-iodopropoxy)-2-nitrobenzyl alcohol (1) is conveniently prepared1 from commercially available 5-hydroxy-2-nitrobenzaldehyde by reaction with 1,3-diiodopropane in the presence of Cs2CO3. The carbonyl functionality of the resultant benzyl ether was then directly reduced to the benzylic alcohol with NaBH4 to give 1 in an overall yield of 92% (1).

Oligosaccharide Synthesis

Photolabile groups have served as linkers for the solid-phase synthesis of oligosaccharides.2-4 Compound 1 has been used as a photocleavable linkage in the synthesis of the heptasaccharide phytoalexin elicitor (HPE) (2).1

Glycosidation of linker 1 with appropriately protected monosaccharide unit 3 gave exclusively b-glycoside 4 in high yield. Attachment of 4, via nucleophilic displacement of the iodide in 4, to hydroxy-functionalized polystyrene resin gave resin-bound monosaccharide 5 (2)

Initial cleavage studies indicated irradiation5,6 of resin 5in THF at 25 °C afforded the released, protected monosaccharide fragment 6 in high yield (95%), signifying the feasibility of using 1 as a linker orthogonal to the other protecting groups on the sugar moiety (3).

This allowed oligosaccharide synthesis, such as the construction of HPE (2), by the iterative addition of monosaccharide fragments. This repetitive procedure involves the sequential selective deprotection of a hydroxy function on the sugar unit attached to the resin followed by glycosidation with a second monosaccharide component. Finally, light-mediated cleavage from the resin followed by global deprotection allowed the isolation of the desired heptasaccharide (as a mixture of a and b anomers).1

Related Reagents.

3-Amino-3-(2-nitrophenyl)propionic acid [5678-48-8];7 3-amino-3-(2-nitrophenyl)-2,2-dimethylpropionic acid;8 4-[4-(1-(9H-fluoren-9-ylmethoxycarbonylamino)-ethyl)-2-methoxy-5-nitrophenoxy]butyric acid [162827-98-7];9 4-[4-(1-hydroxyethyl)-2-methoxy-5-nitrophenoxy)]butyric acid [175281-76-2].10

1. Nicolaou, K. C.; Winssinger, N.; Pastor, J.; DeRoose, F., J. Am. Chem. Soc. 1997, 119, 449.
2. Nicolaou, K. C.; Watanabe, N.; Li, J.; Pastor, J.; Winssinger, N., Angew. Chem. Int. Ed. 1998, 37, 1559.
3. Rodebaugh, R.; Joshi, S.; Fraser-Reid, B.; Geyson, H. M., J. Org. Chem. 1997, 62, 5660.
4. Zehavi, U.; Amit, B.; Patchornik, A., J. Org. Chem. 1972, 37, 2281.
5. Pillai, V. N. R., Synthesis 1980, 1.
6. Patchornik, A.; Amit, B.; Woodward, R. B.; J. Am. Chem. Soc. 1970, 92, 6333.
7. Brown, B. B.; Wagner, D. S.; Geysen, H. M., Molecular Diversity 1995, 1, 4.
8. Sternson, S. M.; Schreiber, S. L., Tetrahedron Lett. 1998, 39, 7451.
9. Holmes, C. P.; Jones, D. G., J. Org. Chem. 1995, 60, 2318.
10. Whitehouse, D. L.; Savinov, S. N.; Austin, D. J., Tetrahedron Lett. 1997, 38, 7851.

Mark Bradley & Stifun Mittoo

University of Southampton, Southampton, UK

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.