59th Annual Report on Research 2014

Thiazolidine chemistry is a commonly used reaction used in biological systems because the reaction requires the presence of both cysteine (a common amino acid) and an aldehyde or ketone. The cysteine residue contains multiple functionalities that be employed to prepare unique materials. We have developed a synthetic route to access three different functional points of the cysteine residue. Futhermore, protected cysteine molecules have been successfully ligated onto polymerizable monomers and have been shown to be easily deprotected in the presence of an acid source.

Scheme 1 Synthesis of protected cysteine.

The synthesis of 1 was simple and efficient. L-cysteine HCl does not appear soluble in acetone, but when refluxed at 80 °C, the solution eventually becomes homogeneous and 1 precipitates out. Various protecting groups were employed with a wide range of synthetic conditions. Ultimately, a mixed anhydride method was employed. The synthesis of 2 was confirmed directly via ¹H NMR after it was recrystallized from methanol and water.

Next, the carboxylic acid functional group was coupling with various amines. Scheme 2 depicts coupling with benzyl amine which was conducted as a control experiment. Other amines, such as allyl amine and propargyl amine have employed to allow for thiol-ene/yne chemistry, furfuryl amine to allow for Diels-Alder chemistry and 4-vinyl benzyl amine for polymerizable monomers, Figure 1.

Scheme 2. Carboxylic acid coupling of protected cysteine.

Figure 1.  Functional protected cysteine compounds prepared.

Protected cysteine residues were incorporated into polymeric resins by the direct polymerization of compound 4, as well as the post-polymerization modification of poly(styrene-co-4-vinyl benzyl azide), Scheme 3.

Scheme 3. Incorporation of protected cysteine into polymeric systems

Future work involves the modification of other resin systems. Additionally compounds 6 and 7 will be utilized as cores for the preparation of miko-arm star polymers via thiol-ene/yne coupling.

In total, four undergraduate students have completed research from support of this award and resulted in two oral presentations given by undergraduate students at the National American Chemical Society meetings.