Lactic 9-carboxyanhydride

Poly(amino acids) are insoluble in common solvents, are difficult to fabricate due to high melting point, and absorb a significant amount of water when their acid content reaches over 50 mol%. To solve these problems, polyesters derived from amino acids and lactic acids [e.g., poly (lactic acid-co-lysine) PLAL] are developed. The PLAL system is further modified by reaction with lysine A-carboxyanhydride derivatives. Another modification of poly(amino acids) includes poly(iminocarbon-ates), which are derived from the polymerization of desaminotyrosyl tyrosine alkyl esters. These polymers are easily processable and can be used as support materials for cell growth due to a high tissue compatibility. Mechanical properties of tyrosine-derived poly(carbonates) are in between those of poly(orthoesters) and poly(lactic acid) or poly(gly-colic acid). The rate of degradation of poly(iminocarbonates) is similar to that of poly (lactic acid). 

Analogous to amino acids, a-hydroxy acids form cyclic anhydrides when treated with phosgene. However, a much more efficient reagent for this transformation with lactic acid is trichloromethyl chloroformate. By this method, L-lactic acid O-carboxyanhydride (3) is prepared as a crystalline solid in 46% yield [2]. Although 3 has found application in polymer chemistry, its use in asymmetric synthesis has been limited. Reaction of 3 with 4-bromo-benzaldehyde methylthio(thiocarbonyl)hydrazone in the presence of TFA gives a mixture of 4 (25%) and 5 (56%), which is separable by column chromatography [3]. 

Zileuton, a potent and selective inhibitor of 5-lipoxygenase, can be prepared in optically active form on a laboratory scale using lactic acid as the chiral source [91] (Scheme 38). The key intermediate, A-carboxyanhydride 268 is formed in 6 steps from 123, and has an optical purity greater than 98%. 

At this point, some alternative methods are worthy of mention for the synthesis of polydepsipeptides. The copolymerization of lactones and amino acid carboxy-anhydrides using stannous octanoate as catalyst affords random polydepsipeptides, and is an attractive way to prepare polymers with pendant functional groups [42]. In addition, the ROP of amino acid N-carboxyanhydrides and lactic acid anhydrosulfite affords polymers the structure of which may be either random or blocky-like , depending on the catalyst/initiator system used [43, 44). 

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