Efforts towards the synthesis of furan containing bioactive compounds

Abstract

Furan is a valuable subunit in pharmaceutical chemistry. However, there are still challenges in synthesizing furan-containing compounds. Two approaches have been attempted to address this issue. 1. Using enynal molecules as a carbene precursor for synthesizing functionalized furyl-pyrrolidines. A cascade approach was developed for synthesizing functionalized (2-furyl)-2-pyrrolidines, showcasing both convergence and remarkable stereoselectivity. This domino process proceeds through an N–H insertion into enynal-derived metal-carbenoid, followed by an intramolecular aldol reaction to provide pyrrolidines with high diastereoselectivity (>98:2). This chemistry utilizes Earthabundant zinc chloride as a catalyst with loading as low as 1 mol%. This method operates under mild conditions and demonstrates high chemoselectivity by accommodating substrates bearing functionalities such as free alcohols, alkenes, and alkynes. 2 Towards the total synthesis of collybolide. Collybolide is a natural product that was first isolated from the fungus Collybia maculata. It has attracted attention due to its potential therapeutic applications, particularly in the treatment of pain and inflammation. Its complex structure, however, makes it a challenging target for total synthesis. Our route starts from simple glutamic acid. This route aimed to minimize the use of chiral reagents and catalysts to install all 6 stereocenters in Collybolide. So far, after 11 reactions, we have achieved the intermediate having 15 out of 22 carbon atoms and 4 out of 6 stereocenters in Collybolide without using any chiral reagents and catalysts other than glutamic acid. One of the significances of this route is that different from the traditional synthetic route, we installed furan moiety at a very early stage. Furan is known for its instability, however, in our route, it is stable throughout the synthetic pathway.