M. Adamczyk, J. Fishpaugh, M. Thiruvazhi
Jun 1, 2002
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0
Influential Citations
6
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Journal
Organic Preparations and Procedures International
Abstract
Water soluble poly(ethyleneglyco1) (PEG) linkers that tether biomolecules have found widespread applications in medicinal chemistry due to their biocompatibility , amphilicity , low immunogenicity and toxicity.'-9 Short bifunctional ethyleneglycol linkers provide the desirable properties of PEG and are extremely attractive materials for bioconjugation.1°-13 We present herein a concise synthesis a series of short bifunctional linkers, the N-protected carboxyalkyl ether amines (Fig. 1). Previous efforts for the preparation of these compounds have been limited to either multi-step sequences or specific preparations that RNH k0k are not adaptable to the preparation of a variety of N-protected carboxyalkyl ether amines.I4I6 Our approach envisioned 0-alkylation of the N-protected amino alcohols la-f with an alkyl bromoacetate followed by ester hydrolysis to afford the desired compounds (Scheme 1). A lack of chemoselective deprotonation in the first step would result in a mixture of products arising from N-alkylation, O-alkylation and/or both. A brief investigation of the effects of temperature and counter-ion on the alkylation CO2H