Molecularly defined (L)-lactic acid oligomers and polymers: Synthesis and characterization

The synthesis of (L)-lactide oligomers from dimer to 64mer via an exponential growth strategy is described. By careful selection of orthogonal protective groups, the synthesis were conducted using a t-butyldimethylsilyl (TBDMS) ether as the protective group of the hydroxyl group and benzyl (Bn) ester as the protective group of the carboxylic acid group. The yields or both the deprotection steps and coupling reactions using 1,3-dicyclohexylcarbodiimide or 1-[3-(dimethylamino)propyl]-3-ethyl carbodiimide hydrochloride were high (70-100%) and the absence of a requirement for conducting the majority of reactions under an inert atmosphere permitted a robust and efficient synthetic strategy to be developed. This allowed monodisperse dimer, tetramer, octamer, 16mer, 32mer, and 64mer materials to be prepared in gram quantities and fully characterized using mass spectrometry and size exclusion chromatography. Evaluation of the thermal and physical properties using thermogravimetric analysis, differential scanning calorimetry, and small angle X-ray scattering demonstrated a close correlation between the molecular structure of the well-defined Poly(lactide) oligomers and their physical properties. (C) 2008 Wiley Periodicals, Inc.