DNA‐Templated [2 2] Photocycloaddition: A Straightforward Entry into the Aplysinopsin Family of Natural Products

Abstract

Biosynthetic considerations inspired us to harness the template properties offered by DNA to promote a [2+2] photo‐induced cycloaddition. The method was developed based on the dimerization of (E)‐aplysinopsin, which was previously shown to be unproductive in solution. In sharp contrast, exposure of this tryptophan‐derived olefin to light in the presence of salmon testes DNA (st‐DNA) reproducibly afforded the corresponding homo‐dimerized spiro‐fused cyclobutane in excellent yields. DNA provides unique templating interactions enabling a singular mimic of the solid‐state aggregation necessary for the [2+2] photo‐cycloaddition to occur. This method was ultimately used to promote the prerequisite dimerizations leading to both dictazole B and tubastrindole B, thus constituting the first example of a DNA‐mediated transformation to be applied to the total synthesis of a natural product.