重氮三环十一烷骨架的合成：金（I）催化的Conia-ene型5-环化反应及逐步取代基组装以构建富含sp的化合物库。

Synthesis of the diazatricycloundecane scaffold gold(I)-catalysed Conia-ene-type 5- cyclization and stepwise substituent assembly for the construction of an sp-rich compound library.

作者信息

Doi Tomoya, Umedera Kohei, Miura Kazuki, Morita Taiki, Nakamura Hiroyuki

机构信息

School of Life Science and Technology, Tokyo Institute of Technology, 4259 Nagatsuta-cho Midori-ku, Yokohama, 226-8503, Japan.

Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, 4259 Nagatsuta-cho Midori-ku, Yokohama, 226-8503, Japan.

出版信息

Org Biomol Chem. 2023 Nov 8;21(43):8716-8726. doi: 10.1039/d3ob01534c.

DOI:10.1039/d3ob01534c

PMID:37869769

Abstract

The bridged diazatricycloundecane sp-rich scaffold was synthesised the gold(I)-catalysed Conia-ene reaction. The electron-donating property of the siloxymethyl group on alkyne 1 enabled 6- cyclization, whereas the ethoxy carbonyl group on alkyne 4 led to 5- cyclization with complete regioselectivity in the Conia-ene reaction. The resulting bridged diazatricycloundecane scaffold 5 allowed the construction of a library of sp-rich compounds. Among the compounds synthesised, compounds 6e and 6f inhibited the hypoxia inducible factor 1 (HIF-1) downstream signaling pathway without affecting HIF-1α mRNA expression.

摘要

通过金（I）催化的科尼亚-烯反应合成了桥连二氮杂三环十一烷富sp骨架。炔烃1上的硅氧基甲基的给电子性质使得能够进行6-环化，而炔烃4上的乙氧基羰基在科尼亚-烯反应中导致5-环化并具有完全的区域选择性。所得的桥连二氮杂三环十一烷骨架5使得能够构建富sp化合物库。在合成的化合物中，化合物6e和6f抑制缺氧诱导因子1（HIF-1）下游信号通路，而不影响HIF-1α mRNA表达。