Environmentally Benign CO2-Based Copolymers: Degradable Polycarbonates Derived from Dihydroxybutyric Acid and Their Platinum-Polymer Conjugates

(S)-3,4-Dihydroxybutyric acid ((S)-3,4-DHBA), an endogenous straight chain fatty acid, is a normal human urinary metabolite and can be obtained as a valuable chiral biomass for synthesizing statin-class drugs. Hence, its epoxide derivatives should serve as promising monomers for producing biocompatible polymers via alternating copolymerization with carbon dioxide. In this report, we demonstrate the production of poly(tertbutyl 3,4-dihydroxybutanoate carbonate) from racemic-tert-butyl 3,4-epoxybutanoate (rac-Bu-t 3,4-EB) and CO2 using bifunctional cobalt(III) salen catalysts. The copolymer exhibited greater than 99% carbonate linkages, 100% head-to-tail regioselectivity, and a glass-transition temperature (T-g) of 37 degrees C. By way of comparison, the similarly derived polycarbonate from the sterically less congested monomer, methyl 3,4-epoxybutanoate, displayed 91.8% head-to-tail content and a lower Tg of 18 degrees C. The tert-butyl protecting group of the pendant carboxylate group was removed using trifluoroacetic acid to afford poly(3,4-dihydroxybutyric acid carbonate). Depolymerization of poly(tert-butyl 3,4-dihydroxybutanoate carbonate) in the presence of strong base results in a stepwise unzipping of the polymer chain to yield the corresponding cyclic carbonate. Furthermore, the full degradation of the acetyl-capped poly(potassium 3,4-dihydroxybutyrate carbonate) resulted in formation of the biomasses, beta-hydroxy-gamma-butyrolacetone and 3,4-dihydroxybutyrate, in water (pH = 8) at 37 degrees C. In addition, water-soluble platinum polymer conjugates were synthesized with platinum loading of 21.3-29.5%, suggesting poly(3,4-dihydroxybutyric acid carbonate) and related derivatives may serve as platinum drug delivery carriers.