L-谷氨酸苄酯与L-丙氨酸共聚物合成研究
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摘要
聚氨基酸是一种低毒、生物降解性和生物相容性好、容易被机体吸收、代谢的生物降解高分子，它的应用非常广泛，如在医学领域中用于药物控释、人造皮肤等方面。
以L-谷氨酸和L-丙氨酸为基本原料，研究两种氨基酸的共聚反应体系。通过L-谷氨酸与苯甲醇反应以苄酯的形式保护γ位上的羧基，生成L-谷氨酸γ-苄酯。在0℃将浓硫酸干燥的光气分别通入L-谷氨酸γ-苄酯和L-丙氨酸的四氢呋喃悬浮乳液中，5h后停止通入光气，缓慢升温至30℃合成得到L-谷氨酸γ-苄酯-N-羧基-环内酸酐(BLG-NCA)和L-丙氨酸-N-羧基-环内酸酐(Ala-NCA)，通过红外证明了反应产物为NCAs。另外，还尝试了用三光气(三氯二甲基碳酸酯)代替光气，简化了反应工艺条件，大大缩减了反应所需的时间。
以三乙胺作为引发剂引发开环聚合制备了BLG—NCA和Ala—NCA共聚物。由固体~(13)C核磁确定共聚物的结构特征。两种单体的竞聚率的测定是通过将共聚物放入过量的盐酸(HCl)中静置过夜经酸性脱酯除去苄基。所得产物经过滤，真空干燥后溶于氢氧化钠溶液中(溶剂为体积比1：1的丙酮和水混合物)，利用旋转蒸发仪蒸干溶液。最后将烘干的产物溶于吡啶中，用PH计测定羧基含量，得到共聚物的组成比，再利用Keien-T(?)d(?)s作图法和最小二乘法计算两种单体的竞聚率。结果表明，BLG-NCA的竞聚率r_1=1.134，Ala-NCA的竞聚率r_2=2.098。
在溶解性方面，L-丙氨酸链节的存在增加的共聚物的难溶性。实验发现BLG—NCA和Ala—NCA共聚物在二氯乙酸中溶解速度较聚L-丙氨酸快，但是除聚L-谷氨酸γ-苄酯外，两者都不能溶解在四氢呋喃中。
聚L-丙氨酸和BLG—NCA和Ala—NCA共聚物的主链都由酰胺键连接而成，通过实验发现BLG—NCA和Ala—NCA共聚物的紫外和微生物降解的程度均比聚L-丙氨酸要大。这可能是共聚物的侧基体积较聚L-丙氨酸大的多，破坏的分子链的规整排列，使溶剂分子容易进入聚合物内部，增加了聚合物与微生物接触机会，同时紫外对共聚物侧基上的酯键也有降解作用。
Poly(amino acids) are a kind of biodegradable polymer materials with low toxicity, excellent biocompatibility, biodegradability and bioabsorbability in vivo. They are very widely used, especially in pharmaceutical and biomedical areas such as drug delivery systems and tissue engineering.
Reaction of copolymerization based on L-glutamic acid and L-alanine was systematically studied. The γ-carboxyl was protected by L-glutamic acid reacted with benzyl alcohol, which could produce the γ-benzyl ester of L-glutamic acid. The excess of gaseous phosgene passed into the suspensions of L-alanine and the γ-benzyl ester of L-glutamic acid respectively at 0℃ and then heated to 30℃ slowly. The N-carboxyanhydride of γ-benzyl ester of L-glutamic acid and N-carboxyanhydride of L-alanine was synthesized, and the IR spectrums show that reactantive products are γ-benzyl ester of L-glutamic acid, L-carboxyanhydride of γ-benzyl ester of L-glutamic acid and N-carboxyanhydride of L-alanine. In addition, the attempt to use trichloromethyl instead of phosgene simplifed experiment apparatus and shortened reaction time to a great extent.
Copolymer of N-carboxyanhydride of γ-benzyl ester of L-glutamic acid and N-carboxyanhydride of L-alanine was prepared in the way of ring-opening in nitrobenzene with triethylamine as initiator at 40℃ and the structural characteristics of copolymer were illuminated through solid state ~(13)C NMR. The intrinsic viscosities of the copolymers were measured in dichloroacetic acid at 30℃ with an Ubblohd capillary viscometer. The copolymers were reacted with hydrochloric acid(0.2 M) for removing benzyl ,filtered and dried under vacuum after being filtered. The obtained copolymers which didn't contained benzyl were dissolved in sodium hydroxide solution (V_(acetone) :V_(water) =1:1) by heating. Superfluous hydrochloric acid(0.2 M) was added into the above solution and dried in the help of rotary evaporator and the obtained polymers were dissolved again in pyridine. The mole ratios of two units in
以L-谷氨酸和L-丙氨酸为基本原料，研究两种氨基酸的共聚反应体系。通过L-谷氨酸与苯甲醇反应以苄酯的形式保护γ位上的羧基，生成L-谷氨酸γ-苄酯。在0℃将浓硫酸干燥的光气分别通入L-谷氨酸γ-苄酯和L-丙氨酸的四氢呋喃悬浮乳液中，5h后停止通入光气，缓慢升温至30℃合成得到L-谷氨酸γ-苄酯-N-羧基-环内酸酐(BLG-NCA)和L-丙氨酸-N-羧基-环内酸酐(Ala-NCA)，通过红外证明了反应产物为NCAs。另外，还尝试了用三光气(三氯二甲基碳酸酯)代替光气，简化了反应工艺条件，大大缩减了反应所需的时间。
以三乙胺作为引发剂引发开环聚合制备了BLG—NCA和Ala—NCA共聚物。由固体~(13)C核磁确定共聚物的结构特征。两种单体的竞聚率的测定是通过将共聚物放入过量的盐酸(HCl)中静置过夜经酸性脱酯除去苄基。所得产物经过滤，真空干燥后溶于氢氧化钠溶液中(溶剂为体积比1：1的丙酮和水混合物)，利用旋转蒸发仪蒸干溶液。最后将烘干的产物溶于吡啶中，用PH计测定羧基含量，得到共聚物的组成比，再利用Keien-T(?)d(?)s作图法和最小二乘法计算两种单体的竞聚率。结果表明，BLG-NCA的竞聚率r_1=1.134，Ala-NCA的竞聚率r_2=2.098。
在溶解性方面，L-丙氨酸链节的存在增加的共聚物的难溶性。实验发现BLG—NCA和Ala—NCA共聚物在二氯乙酸中溶解速度较聚L-丙氨酸快，但是除聚L-谷氨酸γ-苄酯外，两者都不能溶解在四氢呋喃中。
聚L-丙氨酸和BLG—NCA和Ala—NCA共聚物的主链都由酰胺键连接而成，通过实验发现BLG—NCA和Ala—NCA共聚物的紫外和微生物降解的程度均比聚L-丙氨酸要大。这可能是共聚物的侧基体积较聚L-丙氨酸大的多，破坏的分子链的规整排列，使溶剂分子容易进入聚合物内部，增加了聚合物与微生物接触机会，同时紫外对共聚物侧基上的酯键也有降解作用。
Poly(amino acids) are a kind of biodegradable polymer materials with low toxicity, excellent biocompatibility, biodegradability and bioabsorbability in vivo. They are very widely used, especially in pharmaceutical and biomedical areas such as drug delivery systems and tissue engineering.
Reaction of copolymerization based on L-glutamic acid and L-alanine was systematically studied. The γ-carboxyl was protected by L-glutamic acid reacted with benzyl alcohol, which could produce the γ-benzyl ester of L-glutamic acid. The excess of gaseous phosgene passed into the suspensions of L-alanine and the γ-benzyl ester of L-glutamic acid respectively at 0℃ and then heated to 30℃ slowly. The N-carboxyanhydride of γ-benzyl ester of L-glutamic acid and N-carboxyanhydride of L-alanine was synthesized, and the IR spectrums show that reactantive products are γ-benzyl ester of L-glutamic acid, L-carboxyanhydride of γ-benzyl ester of L-glutamic acid and N-carboxyanhydride of L-alanine. In addition, the attempt to use trichloromethyl instead of phosgene simplifed experiment apparatus and shortened reaction time to a great extent.
Copolymer of N-carboxyanhydride of γ-benzyl ester of L-glutamic acid and N-carboxyanhydride of L-alanine was prepared in the way of ring-opening in nitrobenzene with triethylamine as initiator at 40℃ and the structural characteristics of copolymer were illuminated through solid state ~(13)C NMR. The intrinsic viscosities of the copolymers were measured in dichloroacetic acid at 30℃ with an Ubblohd capillary viscometer. The copolymers were reacted with hydrochloric acid(0.2 M) for removing benzyl ,filtered and dried under vacuum after being filtered. The obtained copolymers which didn't contained benzyl were dissolved in sodium hydroxide solution (V_(acetone) :V_(water) =1:1) by heating. Superfluous hydrochloric acid(0.2 M) was added into the above solution and dried in the help of rotary evaporator and the obtained polymers were dissolved again in pyridine. The mole ratios of two units in
引文
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