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

Abstract

Biosynthetic considerations inspired us to harness the templating properties offered by DNA to promote a [2+2] photoinduced 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] photocycloaddition 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.