由糠醛合成双环N,O-缩醛支架及其功能化

Synthesis and functionalization of bicyclic N,O-acetal scaffolds from furfural.

作者信息

van der Pijl Ferdi, van Delft Floris L, Rutjes Floris P J T

机构信息

Radboud University Nijmegen, Institute for Molecules and Materials, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.

出版信息

Bioorg Med Chem. 2015 Jun 1;23(11):2721-9. doi: 10.1016/j.bmc.2014.12.045. Epub 2014 Dec 29.

DOI:10.1016/j.bmc.2014.12.045

PMID:25596167

Abstract

We have synthesized biologically relevant 6-aza-8-oxa[3.2.1]bicyclooctane scaffolds in a five-step procedure starting from furfural. Besides showing that these scaffolds are amenable to decoration via standard functional group interconversions, we also describe investigations for further functionalization via Lewis acid-mediated N,O-acetal opening, followed by nucleophilic trapping of the resulting intermediate cation. By using different nucleophiles, we have successfully prepared a modest library of 2,6-trans-disubstituted pyrans in good yields and in a highly diastereoselective manner.

摘要

我们从糠醛出发，通过五步反应合成了具有生物学相关性的6-氮杂-8-氧杂[3.2.1]双环辛烷骨架。除了表明这些骨架可通过标准官能团转化进行修饰外，我们还描述了通过路易斯酸介导的N,O-缩醛开环，随后对所得中间体阳离子进行亲核捕获以进一步官能化的研究。通过使用不同的亲核试剂，我们成功地以良好的产率和高非对映选择性制备了一个适度的2,6-反式二取代吡喃文库。