Synthesis of biologically active natural products, aspergillides A and B, entirely from biomass derived platform chemicals

Abstract

The depletion of finite fossil fuels drives the need to develop sustainable chemical feedstock such as biomass. The synthesis of biologically active natural products aspergillides A and B was achieved whereby all the carbon atoms present originated from biomass derived platform chemicals such as ethanol, levulinic acid and 5-hydroxymethylfurfural (HMF). The key steps in this synthesis include Noyori's asymmetric transfer hydrogenation, Achmatowicz rearrangement coupled with a triple reduction sequence, micellar Negishi coupling as well as an enzymatic kinetic resolution. Lipshutz's micellar Negishi coupling was also successfully applied on an advanced synthetic intermediate for the first time with good yield and excellent selectivity. This synthesis demonstrates the feasibility of constructing biologically active compounds using a sustainable chemical feedstock like biomass.