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.

An Overview of Aplysinopsins: Synthesis and Biological Activities

“…In advanced research for the same research team, Skiredj and his group [ 41 ] have developed an unprecedented DNA-templated [2 + 2] photodimerization process for synthesizing spiro-fused cyclobutane-containing compounds including the natural heterodimer dictazole B ( 29b ) ( Scheme 6 ).…”

Insights into the Biosynthesis of Cyclic Guanidine Alkaloids from Crambeidae Marine Sponges

“…Lessons learnt from related works led us to envisage straightforward biomimetic approaches respecting,asclosely as possible,the biosynthetic hypothesis. [16] Therefore,a no xidative decarboxylation of arginine (6)w as used to generate the highly reactive pyrrolinium salt 10 in situ (Scheme 2). Silver(II) picolinate [17] was chosen according to Leesp rocedure and permitted the performance of three biomimetic transformations in as ingle pot:1 )oxidative decarboxylation, 2) deamination to form aldehyde 9,and 3) intramolecular dehydration to form 10.T o achieve ac onvergent synthesis,t he suitable fully functionalized b-keto ester 15 was concomitantly prepared.…”