A kind of preparation method of amino protecting group

Abstract

The invention discloses a preparation method of an amino protecting group, which belongs to the field of organic synthesis. The synthesis method specifically includes the following steps: (1) chloromethylating 4-nitrophenol to obtain 2-chloromethyl-4-nitrophenol; (2) adhering 2-chloromethyl-4-nitrophenol to Nitriding gives 2‑azidomethyl‑4‑nitrophenol; (3) 2‑azidomethyl‑4‑nitrophenol reacts with triphosgene to obtain a protecting group (NRT). The protection group of the invention has good stability, high yield and simple removal.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis and relates to a preparation method of an amino protecting group. Background technique [0002] Amino protecting groups are widely used in organic synthesis, especially play an important role in the synthesis of polypeptides. Commonly used amino protecting groups are mainly divided into three categories: alkoxycarbonyl amino protecting groups, acyl amino protecting groups, alkyl Amino-like protecting group. [0003] Alkoxycarbonyl amino protecting groups mainly include benzyloxycarbonyl (Cbz), tert-butoxycarbonyl (Boc), Wat methoxycarbonyl (Fmoc), allyloxycarbonyl (Alloc), trimethylsilylethoxycarbonyl (Teoc) , A (or B) oxycarbonyl group, although these protective groups are widely used, but there are also defects. It is difficult to remove benzyloxycarbonyl (Cbz), such as when it is removed with strong acid or Lewis acid, it will produce benzyl carbocation , if there is a carbocation-c...

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Problems solved by technology

[0003] Alkoxycarbonyl amino protecting groups mainly include benzyloxycarbonyl (Cbz), tert-butoxycarbonyl (Boc), Wat methoxycarbonyl (Fmoc), allyloxycarbonyl (Alloc), trimethylsilylethoxycarbonyl (Teoc) , A (or B) oxycarbonyl group, although these protective groups are widely used, but there are also defects. It is difficult to remove benzyloxycarbonyl (Cbz), such as when it is removed with strong acid or Lewis acid, it will produce benzyl carbocation , if there is a carbocation-capturing group in the molecule, the corresponding by-product will be obtained; tert-butoxycarbonyl (Boc) is stable to alkali, but sensitive to acid, which limits its application to a certain extent; Wat methoxycarbonyl The main advantage of (Fmoc) is that it is stable to acid, but it is too sensitive to alkali, and there are many reaction by-products

[0004] The acyl-type amino protecting group includes phthaloyl (Pht). Compared with general acyl amino acids, Pht-amino acids are not easy to racemize when they are attached to peptides, but they are unstable to alkalis; another example is p-toluenesulfonyl (Tos), It is one of the most stable amino protecting groups, but difficult to remove

[0005] Alkyl amino protecting groups include trityl (Trt), which was used in polypeptide synthesis in the 1950s and was also used to protect various amino groups, but it is very sensitive to acids; benzyl (Bn) is widely used and is Also one of the most stable amino protecting groups, but difficult to remove

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