Abstract
Peptide nucleic acid oligonucleotide conjugates are attracting immense interest currently because of their use in the biomedical and diagnostic field as antigene and molecular sensors. The efficient PNA synthesis methods can reduce their cost and may increase availability for their wider use. Here we described a facile synthesis of the peptide nucleic acid monomer N-(Boc-Aminoethylglycin)thymine Ethyl Ester [Ethyl 2-(N-(2-(( tert -butoxycarbonyl)amino)ethyl)-2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1( 2H )-yl)acetamido)acetate]. The monomer N-(Boc-Aeg)thymine Ethyl Ester has been prepared in a good yield (96%) by highly efficient procedure involving direct coupling of nucleobase thymine with the backbone Ethyl N-(Boc-aminoethyl)-N-(chloroacetyl)glycinate, which was prepared from the reaction of Ethyl N-[(2-Boc-amino)-ethyl]glycinate with chlroacetylchloride. The key intermediate Ethyl N-[(2-Boc-amino)-ethyl]glycinate involved in the synthesis has been prepared via a scalable and cost-effective route with a yield of (98%). The thyminyl PNA monomer was reported to be used in various synthetic applications, and our cost-effective, highly scalable method of synthesis will expand its wider use.

Graphic abstract
A new method for the synthesis of Thymine-based PNA monomer precursor N-(Boc-Aeg)thymine Ethyl Ester in gram scale with high purity is reported here. In this method, the use of expensive coupling reagents is avoided.

中文翻译：

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合成N-（Boc-氨基乙基甘氨酸）胸腺嘧啶乙酯的简便方法，用于合成PNA-寡核苷酸共轭物

摘要
肽核酸寡核苷酸偶联物由于其在生物医学和诊断领域中作为抗原和分子传感器的用途而引起了极大的兴趣。有效的PNA合成方法可以降低其成本，并可以提高其广泛使用的可用性。在这里我们描述了肽核酸单体N-（Boc-氨基乙基甘氨酸）胸腺嘧啶乙基酯[乙基2-（N-（2-（（ 叔丁氧基 羰基）氨基）乙基）-2-（5-甲基- 2,4-二氧-3,4-二氢嘧啶-1（ 2H ）-基）乙酰氨基）乙酸]。N-（Boc-Aeg）胸腺嘧啶乙基酯是通过高效方法制备的，收率很高（96％），涉及核碱基胸腺嘧啶与骨架N-（Boc-氨基乙基）-N-（氯乙酰基）的直接偶联。 N-[（2-Boc-氨基）-乙基]甘氨酸乙酯与氯乙酰氯反应制得的甘氨酸盐。合成中涉及的关键中间体N-[（2-Boc-氨基）-乙基]甘氨酸乙酯已 通过 可扩展且具有成本效益的途径制备 ，产率为（98％）。据报道，胸腺嘧啶PNA单体可用于各种合成应用，而我们具有成本效益，高度可扩展的合成方法将扩大其广泛用途。

图形摘要
本文报道了一种以克规模合成高纯度的基于胸腺嘧啶的PNA单体前体N-（Boc-Aeg）胸腺嘧啶乙基酯的新方法。在这种方法中，避免了使用昂贵的偶联剂。