Department of Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10-14, 55128, Mainz, Germany.
Chemistry. 2022 Sep 6;28(50):e202201523. doi: 10.1002/chem.202201523. Epub 2022 Jul 13.
Amaryllidaceae alkaloids appeal to organic chemists with their attractive structures and their impressive antitumor and acetylcholinesterase inhibitory properties. We demonstrate a highly versatile access to this family of natural products. A general protocol with high yields in a sustainable electro-organic key transformation on a metal-free anode to spirodienones facilitates functionalization to the alkaloids. The biomimetic syntheses start with the readily available, inexpensive biogenic starting materials methyl gallate, O-methyl tyramine, and vanillin derivatives. Through known dynamic resolutions, this technology provides access to both enantiomeric series of (epi-)martidine, (epi-)crinine, siculine, and galantamine, clinically prescribed for the treatment of Alzheimer's disease.
石蒜科生物碱以其诱人的结构和显著的抗肿瘤及乙酰胆碱酯酶抑制活性引起了有机化学家的关注。我们展示了一种对这类天然产物具有广泛适用性的合成方法。在无金属阳极的可持续电有机关键转化中，一种高产的通用方案可以得到螺二烯酮，从而实现生物碱的功能化。仿生合成从易得、廉价的生物起始原料没食子酸甲酯、O-甲基酪胺和香草醛衍生物开始。通过已知的动态拆分，该技术可获得（表）马替丁、（表）血根碱、西库林和加兰他敏的两个对映体系列，这些化合物被临床用于治疗阿尔茨海默病。
