Deoxyradicinin

A novel synthetic strategy for obtainment of (±)-3-deoxyradicinin (2) is reported. This synthetic methodology is more efficient than those previously reported in the literature and also shows higher versatility towards the introduction of different side-chains at both C-7 and C-2. The obtained compound (±)-2 shows phytotoxicity against the grass-weed buffelgrass comparable to that of the natural phytotoxin radicinin (1). Therefore, (±)-2 can constitute a more practical synthetic alternative to 1 as bioherbicide for buffelgrass control.

Pierce's disease of grapevine and citrus huanglongbing are caused by the bacterial pathogens Xylella fastidiosa and Candidatus Liberibacter asiaticus (CLas), respectively. Both pathogens reside within the plant vascular system, occluding water and nutrient transport, leading to a decrease in productivity and fruit marketability and ultimately death of their hosts. Field observations of apparently healthy plants in disease-affected vineyards and groves led to the hypothesis that natural products from endophytes may inhibit these bacterial pathogens. Previously, we showed that the natural product radicinin from Cochliobolus sp. inhibits X. fastidiosa. Herein we describe a chemical synthesis of deoxyradicinin and establish it as an inhibitor of both X. fastidiosa and Liberibacter crescens, a culturable surrogate for CLas. The key to this three-step route is a zinc-mediated enolate C-acylation, which allows for direct introduction of the propenyl side chain without extraneous redox manipulations.

Radicinin is a phytotoxic and antibiotic metabolite produced by some phytopathogenic fungi. Precursor administration and cell-free experiments with deoxyradicinin and radicinin were carried out in Bipolaris coicis H13-3. When deoxyradicinin was administered to the fungus, radicinin and 3-epi-radicinin formed. When radicinin administered, 3-epi-radicinin was formed. Their formation was confirmed by cell-free experiments. Deoxyradicinin 3-monooxygenase which catalyzes conversion of deoxyradicinin to radicinin showed the best activity at 35 °C and pH 7.0, and required NAD+ as co-enzyme. Its molecular weight was determined to be 130-184 kDa. Radicinin epimerase catalyzing the reaction of radicinin to 3-epi-radicinin was purified from a cell-free extract. Radicinin epimerase is a homodimer of a 28 kDa subunit, and its highest activity was achieved at 30-35 °C and pH 7.0-9.0.