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手性 TFA 保护的 α-氨基芳基-酮衍生物的合成，通过 α-氨基酸 N-羟基琥珀酰亚胺酯的 Friedel-Crafts 酰化反应。

Synthesis of Chiral TFA-Protected α-Amino Aryl-Ketone Derivatives with Friedel-Crafts Acylation of α-Amino Acid N-Hydroxysuccinimide Ester.

机构信息

Division of Applied Bioscience, Graduate School of Agriculture, Hokkaido University, Kita 9, Nishi 9, Kita-ku, Sapporo 060-8589, Japan.

出版信息

Molecules. 2017 Oct 17;22(10):1748. doi: 10.3390/molecules22101748.

DOI:10.3390/molecules22101748
PMID:29039791
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6151496/
Abstract

Chiral -protected α-amino aryl-ketones are one of the useful precursors used in the synthesis of various biologically active compounds and can be constructed via Friedel-Crafts acylation of -protected α-amino acids. One of the drawbacks of this reaction is the utilization of toxic, corrosive and moisture-sensitive acylating reagents. In peptide construction via amide bond formation, -hydroxysuccinimide ester (OSu), which has high storage stability, can react rapidly with amino components and produces fewer side reactions, including racemization. This study reports the first synthesis and utilization of -trifluoroacetyl (TFA)-protected α-amino acid-OSu as a potential acyl donor for Friedel-Crafts acylation into various arenes. The TFA-protected isoleucine derivative and its diastereomer TFA-protected -isoleucine derivative were investigated to check the retention of α-proton chirality in the Friedel-Crafts reaction. Further utilization of OSu in other branched-chain and unbranched-chain amino acids results in an adequate yield of TFA-protected α-amino aryl-ketone without loss of optical purity.

摘要

手性保护的 α-氨基芳基酮是合成各种生物活性化合物的有用前体之一，可通过保护的 α-氨基酸的 Friedel-Crafts 酰化反应构建。该反应的一个缺点是使用了有毒、腐蚀性和吸湿的酰化试剂。在通过酰胺键形成构建肽时，具有高储存稳定性的 -羟基琥珀酰亚胺酯 (OSu) 可以与氨基成分快速反应，产生较少的副反应，包括外消旋化。本研究报告了首例合成和利用 -三氟乙酰 (TFA)-保护的 α-氨基酸-OSu 作为 Friedel-Crafts 酰化进入各种芳环的潜在酰基供体。研究了 TFA 保护的异亮氨酸衍生物及其非对映异构体 TFA 保护的 -异亮氨酸衍生物，以检查 α-质子手性在 Friedel-Crafts 反应中的保留情况。在其他支链和非支链氨基酸中进一步利用 OSu，可得到足够产率的 TFA 保护的 α-氨基芳基酮，而不会损失光学纯度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09c4/6151496/e42d315c092d/molecules-22-01748-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09c4/6151496/94deab9789db/molecules-22-01748-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09c4/6151496/f13ed3a7521a/molecules-22-01748-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09c4/6151496/e42d315c092d/molecules-22-01748-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09c4/6151496/94deab9789db/molecules-22-01748-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09c4/6151496/f13ed3a7521a/molecules-22-01748-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09c4/6151496/e42d315c092d/molecules-22-01748-sch002.jpg

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本文引用的文献

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