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

Nicolas Duchemin (1) , Adam Skiredj (2, 3) , Justine Mansot (4) , Karine Leblanc (3) , Jean-Jacques Vasseur (4) , Mehdi Beniddir (3) , Laurent Evanno (3) , Erwan Poupon (2, 3) , Michaël Smietana (4) , Stellios Arseniyadis (1)

1 QMUL - Queen Mary University of London
2 MBCIS - Molécules bioactives, conception, isolement et synthèse
3 BioCIS - Biomolécules : Conception, Isolement, Synthèse
4 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]

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.

Mots clés: SELECTIVITY; PHOTOREACTIONS; PHOTOCHEMISTRY; ALKALOIDS; GUANIDINIUM; COMPLEXES; BINDING; DIMERS; CATALYSIS; STONY CORAL

Domaines: Chimie; Chimie organique; Chimie analytique; Catalyse; Chimie thérapeutique

Nicolas Duchemin, Adam Skiredj, Justine Mansot, Karine Leblanc, Jean-Jacques Vasseur, et al.. DNA-Templated [2+2] Photocycloaddition: A Straightforward Entry into the Aplysinopsin Family of Natural Products. Angewandte Chemie International Edition, 2018, 57 (36), pp.11786-11791. ⟨10.1002/anie.201806357⟩. ⟨hal-02197152⟩