Elsevier

Tetrahedron

Volume 60, Issue 50, 6 December 2004, Pages 11565-11569
Tetrahedron

Synthesis of a biotinated amphiphile

https://doi.org/10.1016/j.tet.2004.09.063Get rights and content

Abstract

The synthesis of a biotinated amphiphile assembled from d-(+)-biotin, ethylene diamine as spacer, galactaric acid and 1-dodecylamine was achieved in six steps. The key step was the synthesis of a bisacetonide protected galactaric ester, the structure of which was determined by X-ray analysis. Aminolysis, spacer attachment, coupling with biotin and deprotection led to the amphiphilic galactaramide.

Introduction

The controlled self-assembly of specific amphiphilic molecules, leading to defined and stable bilayer systems and micelles, represents a challenge for fundamental research and has potential nanotechnological applications. To attain this goal a tailor-made design of amphiphilic building blocks containing encoded structural information on their potential specific supramolecular assembly is needed. In the course of our investigations in the field of artificial amphiphils and liposomes,1, 2, 3 the preparation of the biotinated amphiphilic galactaramide 8 was designed. Similar to long-chain alkylaldonamides, which form micellar fibrous aggregates,4, 5 the N-dodecylgalactaramide with its hydrophobic aliphatic dodecyl chain serves as the amphiphilic scaffold. The hydrophilic aldaric acid moiety is expected to induce specific aggregation motifs within micelles or liposomes. The biotin unit, attached by a spacer to the second carboxylic group of galactaric acid (mucic acid), should act as a transmembrane anchor in intercalation experiments into synthetic lecitin bilayer membranes2a and act as a biological marker towards streptavidin and avidin.6

Section snippets

Results and discussion

Galactaric acid (1) was transformed into dimethyl galactarate (2) with a mixture of methanol and concd sulfuric acid under reflux conditions7 in 89% yield (Scheme 1). The resulting dimethyl ester 2 was further protected as dimethyl (2,3:4,5-di-O-isopropylidene)galactarate (3) by heating in dry acetone with anhydrous ferric chloride8 obtaining a brown oil after flash chromatography on silica gel with chloroform/methanol 1:1, and methanol. This brown oil could be transformed into colourless

Conclusion

The synthesis of the biotinated glycolipid 8 was accomplished in six steps. This compound is an example of a new class of possible liposome forming substances that could be employed in the delivery of drugs in the body either by using them alone or as highly functionalized additives to conventional micelle or liposome producing amphiphiles such as phosphorglycerides. The chiral information in the sugar scaffold might be able to induce the formation of chiral assemblies such as micelles,

General

All chemicals were distilled or dried prior to use. Chromatography was performed on Cellulose MN 2100ff from Macherey-Nagel (Düren). Differential Scanning Calorimetry was done with the DSC821e, Mettler Toledo (Gießen). NMR spectra were determined with JNM EX 400, JNM GX 400, and ALPHA 500 spectrometers, JEOL (Tokyo, Japan). X-ray analysis was performed with the X-ray diffractometer Kappa CCD, Nonius (Solingen). Melting points were determined with an IA 9100, Electrothermal (Southend-on-Sea, UK)

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