3-Acetyloxy-2-cyano-2-(alkylaminocarbamoyl)propyl groups as biodegradable protecting groups of nucleoside 5´-mono-phosphates.
3-Acetyloxy-2-cyano-2-(alkylaminocarbamoyl)propyl groups as biodegradable protecting groups of nucleoside 5´-mono-phosphates.
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DOI：
10.3390/molecules16010552
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发表时间：
2011-01-14
期刊：
影响因子：
--
通讯作者：
Lönnberg H
中科院分区：
文献类型：
--
作者：
Ora M;Mäntyvaara A;Lönnberg H
制备了胸苷5 ′-双[3-乙酰氧基-2-氰基-2-（2-苯乙基氨基甲酰基）丙基]磷酸盐（1），并通过HPLC跟踪了猪肝羧酸酯酶（HLE）在pH 7.5和37 °C下对磷酸盐保护基的去除。第一个可检测的中间体是单脱乙酰化三酯14的（RP）-和（SP）-非对映异构体，其随后同时进行逆羟醛缩合成二酯4和酶催化水解成完全脱乙酰化三酯15。前一种途径占主导地位，占14种总分解的90%。二酯4进行酶促脱乙酰化比三酯低700倍，但最终得到胸苷5 ′-单磷酸作为所需的主要产物。为了阐明脱保护后释放的亲电2-氰基-N-（2-苯乙基）丙烯酰胺副产物17的潜在毒性，还研究了谷胱甘肽（GSH）存在下1的水解。
Thymidine 5´-bis[3-acetyloxy-2-cyano-2-(2-phenylethylcarbamoyl)propyl]phosphate (1) has been prepared and the removal of phosphate protecting groups by hog liver carboxyesterase (HLE) at pH 7.5 and 37 °C has been followed by HPLC. The first detectable intermediates are the (RP)- and (SP)-diastereomers of the monodeacetylated triester 14, which subsequently undergo concurrent retro-aldol condensation to diester 4 and enzyme-catalyzed hydrolysis to the fully deacetylated triester 15. The former pathway predominates, representing 90% of the overall breakdown of 14. The diester 4 undergoes the enzymatic deacetylation 700 times less readily than the triester, but gives finally thymidine 5´-monophosphate as the desired main product. To elucidate the potential toxicity of the electrophilic 2-cyano-N-(2-phenylethyl)acrylamideby-product 17 released upon the deprotection, the hydrolysis of 1 has also been studied in the presence of glutathione (GSH).
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影响因子：
2.7
作者：
Padmanabhan, S;Coughlin, JE;Iyer, RP
通讯作者：
Iyer, RP
DOI：
10.1039/b101754n
发表时间：
2001-01-01
期刊：
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2
影响因子：
--
作者：
Ora, M;Mäki, E;Lönnberg, H
通讯作者：
Lönnberg, H
影响因子：
--
作者：
Arimilli, MN;Kim, CU;Bischofberger, N
通讯作者：
Bischofberger, N
影响因子：
7.3
作者：
Choi, JR;Cho, DG;Kim, YZ
通讯作者：
Kim, YZ
影响因子：
3.6
作者：
Ora, Mikko;Taherpour, Sharmin;Lonnberg, Harri
通讯作者：
Lonnberg, Harri