Wang Yuanze, Patil Pravin, Kurpiewska Katarzyna, Kalinowska-Tluscik Justyna, Dömling Alexander
University of Groningen , Department of Drug Design, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Jagiellonian University , Faculty of Chemistry, Department of Crystal Chemistry and Crystal Physics, Biocrystallography Group, Ingardena 3, 30-060 Krakow, Poland.
ACS Comb Sci. 2017 Mar 13;19(3):193-198. doi: 10.1021/acscombsci.7b00009. Epub 2017 Feb 17.
Isocyanide-based multicomponent reactions (IMCR) are by far the most versatile reactions that can construct relatively complex molecules by one-pot synthesis. More importantly, the development of post IMCR modifications significantly improves the scaffold's diversity. Here, we describe the use of N-Boc protected hydrazine together with α-amino acid derived isocyanides in the Ugi tetrazole reaction and its post cyclization under both acidic and basic conditions. The cyclization in acidic conditions was conducted in a one pot fashion, which give 7-aminotetrazolopyrazinone (6) and tetrazolotriazepinone (7) cyclic products. The post cyclization under basic condition could selectively afford Boc-protected 7-aminotetrazolopyrazinone (8) products in yield of 38-87%.
异腈基多组分反应（IMCR）是目前最为通用的反应，能够通过一锅法合成构建相对复杂的分子。更重要的是，IMCR后修饰的发展显著提高了支架的多样性。在此，我们描述了在Ugi四唑反应中使用N-Boc保护的肼与α-氨基酸衍生的异腈，以及在酸性和碱性条件下的环化后反应。酸性条件下的环化以一锅法进行，得到7-氨基四唑并吡嗪酮（6）和四唑并三氮杂庚三酮（7）环状产物。碱性条件下的环化后反应能够选择性地得到Boc保护的7-氨基四唑并吡嗪酮（8）产物，产率为38 - 87%。
