Phomactinine: proposed Retrosynthesis and Forward Synthesis Routes

Abstract

Phomactinine, a newly discovered substance separated from marine fungal secretion, is the first discovered nitrogen-bearing phomactin.1 In this work, a total synthesis for phomactinine is proposed. Initiating from making an α, β-unsaturated Weinreb amide, the synthesis undergoes a [4+2] cycloaddition, followed by a carbon chain elongation. After a [2+2] addition under photochemical condition, a side chain is added, in which process an epoxide forms. Then, ways to close the nitrogen bearing ring are suggested. The route ends with forming a phosphorous ylide intermediate, which leads to the closure of the 11-carbon-ring by Wittig reaction. In this synthesis scheme, an innovative approach of differentiating carbonyl groups with similar reactivity by utilizing the different stability of carbon rings is suggested. This paper proposed the first total synthesis for phomactinine.