Mm. Bear et al., Biosynthetic stereocopolymer of 3-methylmalic acid as hydrolyzable and biocompatible polyester for temporary therapeutic applications, POLYMER, 40(23), 1999, pp. 6521-6528
A mixture of (2S,3S) and (2S,3R)-3-methylaspartic acid, obtained by bioconv
ersion of mesaconic acid in the presence of 3-methyl-aspartase as enzymatic
catalyst, was transformed into the corresponding benzyl 3-methylmalolacton
ate stereoisomers using a multiple-step synthesis. A mixture of (3R,3R) and
(3S,4R) (80/20 (mol/mol) ratio) benzyl-3-methylmalolactonate was transform
ed by anionic ring-opening polymerization to an optically active and stereo
regular stereocopolymer constituted by 80 mol% of benzyl (3R,3S) 3-methylma
late repeating units and 20 mol% of benzyl (3S,4S) 3-methylmalate units, as
determined by H-1 NMR. The corresponding optically active poly(beta-3-meth
ylmalic acid) was obtained by catalytic hydrogenolysis of the protecting be
nzyl ester groups, in N-methylpyrrolidone as solvent. This functionalized h
ydrosoluble polyester was degraded by simple hydrolysis in a phosphate buff
er at pH 7, as shown by SEC measurements. It is worth noting that the kinet
ic profile was equivalent to the one of poly(P-malic acid). Moreover, at 37
degrees C, the hydrolysis was complete within six weeks, yielding to the c
orresponding optically active 3-methylmalic acid. In order to use this poly
meric material for temporary therapeutic applications, polymers containing
both diastereoisomers as repeating units as well as their ultimate products
of degradation were evaluated based on harmlessness towards their environm
ent. No toxicity was detected against a human cell line, HepG2. (C) 1999 El
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