Fast and Convenient Synthesis of Amine-Terminated Polylactide as a Macroinitiator for -Benzyloxycarbonyl-L-Lysine-N-Carboxyanhydrides

Amine-terminated poly (L-lactide) (NH2-PLLA) with various chain lengths were successfully synthesized by sequential tert-butyl-N-(3-hydroxypropyl) carbamate initiated bulk ring-opening polymerization (ROP) of L-lactide (L-LA) in the presence of Stannous(II) 2-ethylhexanoate (Sn(Oct)2) and deprotection of the N-tert-butoxycarbonyl (Boc) group at the end of the polymer chain. The polymers obtained were characterized by FT-IR, 1H NMR, and GPC method. NH2-PLLA thus prepared was used to initiate the polymerization of ω-benzyloxycarbonyl-L-lysine-N-carboxyanhydride (Lys (Z)-NCA), and the result confirmed the high nucleophilicity of the terminal amine group. This method was not only suitable for the preparation of low molecular weight NH2-PLLA, but also quite efficient in the synthesis of high molecular weight samples. 1. Introduction During the last few years, aliphatic polyesters based on hydroxyalkanoic acid, such as polylactides (PLLA), polyglycolide (PGA), poly (caprolactone) (PCL), and their copolymers have become the most important biopolymers because of their biodegradability and good biocompatibility for pharmaceutical and biomedical applications. However, the scope of further application of PLLA is limited for the lacking of highly reactive groups as triggers of chemical reaction, and the surface of PLLA is very hydrophobic [1]. Chemical modification, especially end functionalization, is an important method to expand the applications area of these polymers [2]. The end-functionalized polymers are also important intermediates which can react at the end of the chain with other molecules containing reactive groups such as acid chlorides, sulfonyl chlorides, acid anhydrides, and activated esters for the synthesis of novel polymeric materials [3, 4]. NH2-PLLA can be used to conjugate with lactose to form a new bioabsorbable material which shows high biodegradability and gives a microphase separation structure [1]. Especially, they were investigated as a macroinitiator for the ring-opening polymerization (ROP) of amino acid N-carboxyanhydrides (NCAs) to prepare a block copolymer containing polypeptide segments which showed quite different properties from other polymers [5–14]. The synthesis of NH2-PLLA was based on a method first reported by Gotsche et al. in 1995 [5]. The main idea of his point was capping the hydroxyl end group of PLLA with BOC-L-Phe which containing a protective amino group using N,N′-dicyclohexylcarbodiimide (DCC) as the condensing agent. However, conversion of the hydroxyl group into an N-protected amino acid ester with the acylation