Photocatalyzed cascade for synthesis of the tetracyclic core of akuamiline alkaloids

by Wang, Qile; Zheng, Nan

The Akuammiline alkaloid family that features the complex tetracyclic core structures displays a broad range of biol. activity, such as the reversal of drug resistance in drug-resistant KB cells by aspidophylline A, anti-inflammatory activity through inhibition of the 5-lipoxygenase enzyme by picrinine. we envision that diverse substituent pattern can be installed if substituents are introduced on cyclopentyl ring which stems from 1, 4-diiodoalkanes. Different functional groups should be compatible with carbocation 1, 2-shift thus to address the constraint of the ester functional group. We propose under our system, this core structure can be broken down to three different modules consisted of amino Ph boronic esters , homopropargyl alcs. and 1, 4-diiodobutanes . Such construction can allow us to quickly assemble different substituents on aryl rings, different nucleophiles such as protected amino groups, alc. and most importantly, varies substituents on C-16. Such convergent synthesis is important for SAR studies as each module can be easily modified from simple mols. thus we reported a convergent synthesis of akuammiline alkaloid core strutures through photo cascade reaction. Decorations on multiple positions are achieved through this method and mechanism of key 1,2-shift selectivities are discussed.