Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via A. Moro 2, 53100 Siena, Italy.
Dipartimento di Chimica "Ugo Schiff" (DICUS), Università degli Studi di Firenze, Via della Lastruccia 13, 50019 Sesto Fiorentino, Italy.
Molecules. 2022 Jul 25;27(15):4762. doi: 10.3390/molecules27154762.
A general method for the synthesis of pyrrolizidine derivatives using an intramolecular hydroaminomethylation protocol (HAM) under microwave (MW) dielectric heating is reported. Starting from a 3,4-bis(benzyloxy)-2-[(benzyloxy)methyl]-5-vinylpyrrolidine, MW-assisted intramolecular HAM in the presence of gaseous H and CO gave the natural alkaloid hyacinthacine A protected as benzyl ether. The same approach gave a lentiginosine analogue starting from the corresponding vinyl -hydroxypyrrolidine. The nature of the reaction products and the yields were strongly influenced by the relative stereochemistry of the starting pyrrolidines, as well as by the catalyst/ligand employed. The use of ethanol as a solvent provides environmentally friendly conditions, while the ligand/catalyst system can be recovered by separating the alkaloid product with an SCX column and recycling the ethanolic solution. HAM worked up to three times with the recycled catalyst solution without any significant impact on yield.
本文报道了一种在微波（MW）介电加热条件下，通过分子内羟胺甲基化（HAM）反应合成吡咯里西啶衍生物的通用方法。以 3,4-双（苄氧基）-2-[(苄氧基)甲基]-5-乙烯基吡咯烷为起始原料，在 H 和 CO 的存在下，MW 辅助的分子内 HAM 反应得到了天然生物碱海葱定 A 的苄醚保护产物。从相应的乙烯基-羟吡咯烷出发，采用相同的方法得到了一个莱替丁醇类似物。反应产物的性质和产率强烈受到起始吡咯烷的相对立体化学以及所使用的催化剂/配体的影响。使用乙醇作为溶剂可以提供环境友好的条件，而通过 SCX 柱分离生物碱产物并回收乙醇溶液，可以回收配体/催化剂体系。HAM 可以与回收的催化剂溶液重复使用三次，而对产率没有任何显著影响。
