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Acylated poly-L-lysine derivatives have been used as drug carriers. Acylation was necessary to avoid both toxicity and nonspecific binding to mammalian cells caused by the polycationic properties. (a) Nègre, E.; Monsigny, M.; Mayer, R. Tetrahedron 1993, 49, 6991. (b) Gonsho, A.; Irie, K.; Susaki, H.; Iwasawa, H. Biol. Pharm. Bull. 1994, 17, 275.
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In this paper, poly-L-lysine derivatives are designated as L, poly-D/L-lysine derivatives are designated as D/L, and poly-D-lysine derivatives are designated as D. Polymer identification numbers without an extension do not specify the configuration.
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87
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0345197111
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n = 1.2) with chloroacetic acid anhydride in DMF/ 2,6-lutidine gave an impure material. A clean product was obtained when the hydrobromide was transformed into the DMF-soluble tosylate prior to the acylation (for the transformation of polylysine hydrobromide into its tosylate, see ref 23a).
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88
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note
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L-8 and all other polymers described are also soluble in DMF and DMSO.
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Quantitative carbohydrate incorporation was also achieved when the sodium thiolate of 11 was used, which was prepared from 11 by treatment with 1 equiv of sodium methanolate.
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This method has been described earlier in a patent. (a) Thoma, G.; Duthaler, R. O.; Ernst, B.; Magnani, J. L.; Patton, J. T. PCT Int. Appl., WO 97/19105, 1997. A similar procedure has recently been published. (b) Blixt, O.; Norberg, T. J. Carbohydr. Chem. 1997, 16, 143.
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0344766607
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note
-
Compound 10 (5:1 α/β-mixture) was obtained from the corresponding tetraacetate by saponification using sodium methanolate in methanol. The reaction mixture was neutralized with Dowex 50Wx8 ion-exchange resin.
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