Base dependent 1,3-dithioacetals rearrangement over sulfoxidation under visible-light photocatalysis to access disulfide-linked-dithioesters

Base dependent oxidative rearrangement of dithiolanes and dithianes to access disulfide-linked-dithioesters under visible-light photoredox catalytic conditions has been disclosed. The protocol demonstrated the ability to synthesize either rearranged product or sulfoxide by simply switching the base with inherent ability to make hydrogen bonding with sulfur atom. Unlike, the usual deprotection of thioacetals to corresponding aldehydes under the oxidative conditions, we observed the unique regioselective oxidative reactivity of thioacetals to form disulfide-linked-dithioester or sulfoxides. The generality of the protocol has been demonstrated by exploring a wide range of substrates. As an application the in-situ generated thyil radical has been trapped with disulfides to prepare hetro-disulfides of potential utility. The protocol proved to be practical on gram scale quantity and relied on clean energy source for the transformation. Based on the series of control experiments, cyclic volametry and Stern-Volmer studies the plausible mechanism has been proposed.

Methanol-Driven Oxidative Rearrangement of Biogenic Furans – Enzyme Cascades vs. Photobiocatalysis

The oxidative ring expansion of bio-derived furfuryl alcohols to densely functionalized six-membered O-heterocycles represents an attractive strategy in the growing network of valorization routes to synthetic building blocks out of the lignocellulosic biorefinery feed. In this study, two scenarios for the biocatalytic Achmatowicz-type rearrangement using methanol as terminal sacrificial reagent have been evaluated, comparing multienzymatic cascade designs with a photo-bio-coupled activation pathway.

Enzymatic spiroketal formation via oxidative rearrangement of pentangular polyketides

The structural complexity and bioactivity of natural products often depend on enzymatic redox tailoring steps. This is exemplified by the generation of the bisbenzannulated [5,6]-spiroketal pharmacophore in the bacterial rubromycin family of aromatic polyketides, which exhibit a wide array of bioactivities such as the inhibition of HIV reverse transcriptase or DNA helicase. Here we elucidate the complex flavoenzyme-driven formation of the rubromycin pharmacophore that is markedly distinct from conventional (bio)synthetic strategies for spiroketal formation. Accordingly, a polycyclic aromatic precursor undergoes extensive enzymatic oxidative rearrangement catalyzed by two flavoprotein monooxygenases and a flavoprotein oxidase that ultimately results in a drastic distortion of the carbon skeleton. The one-pot in vitro reconstitution of the key enzymatic steps as well as the comprehensive characterization of reactive intermediates allow to unravel the intricate underlying reactions, during which four carbon-carbon bonds are broken and two CO2 become eliminated. This work provides detailed insight into perplexing redox tailoring enzymology that sets the stage for the (chemo)enzymatic production and bioengineering of bioactive spiroketal-containing polyketides.