Castillo-Garcia Antonio A, Haupenthal Jörg, Hirsch Anna K H, Barta Katalin
Institute of Chemistry, University of Graz Heinrichstrasse 28/II A-8010 Graz Austria
Stratingh Institute for Chemistry, University of Groningen Nijenborgh 4, 9747 AG Groningen The Netherlands.
RSC Sustain. 2025 Jul 2. doi: 10.1039/d5su00151j.
Reductive catalytic fractionation (RCF) has emerged as a centrally important method in modern biorefining, delivering well-defined aromatic platform chemicals from lignin with high selectivity. To establish attractive future biorefinery schemes, urgent attention needs to be devoted to the development of sustainable catalytic methods for the downstream conversion of these aromatic platform chemicals. In this regard, the efficient production of structurally complex, biologically active amines with high atom and step economy represents an attractive goal. Herein, we describe the development of novel catalytic pathways for converting prominent lignin-derived guaiacols that originated during RCF processing into different series of six-membered N-heterocycles, applying hydrogen borrowing amination and C-N cross coupling as key catalytic steps. Specifically, 4-propanol guaiacol (1G) was converted into 1,2,3,4-tetrahydroquinolines 1Gd, whereas the formation of benzomorpholines 2-3Gd from 4-propyl guaiacol (2G) and 4-ethyl guaiacol (3G) was achieved. The biological activity of the developed compound libraries was evaluated in terms of anticancer activity using human HepG2 cells, which displayed promising activity in several examples.
还原催化分馏（RCF）已成为现代生物精炼中一项至关重要的核心方法，能够从木质素中以高选择性产出结构明确的芳香族平台化学品。为构建具有吸引力的未来生物精炼方案，迫切需要关注用于这些芳香族平台化学品下游转化的可持续催化方法的开发。在这方面，以高原子经济性和步骤经济性高效生产结构复杂的生物活性胺是一个具有吸引力的目标。在此，我们描述了新型催化途径的开发，该途径将RCF过程中产生的主要木质素衍生愈创木酚转化为不同系列的六元氮杂环，采用氢转移胺化和C-N交叉偶联作为关键催化步骤。具体而言，4-丙醇愈创木酚（1G）被转化为1,2,3,4-四氢喹啉1Gd，而由4-丙基愈创木酚（2G）和4-乙基愈创木酚（3G）形成苯并吗啉2-3Gd得以实现。使用人肝癌细胞系HepG2对所开发化合物库的生物活性进行了抗癌活性方面的评估，在多个实例中显示出了有前景 的活性。
