Boscalid

Boscalid is a broad spectrum fungicide used in agriculture to protect crops from fungal diseases. It was first marketed by BASF in 2002 using their brand name Endura. The compound is an biphenyl amide derived inhibitor of succinate dehydrogenase.

History
Inhibition of succinate dehydrogenase, the complex II in the mitochondrial respiration chain, has been known as a fungicidal mechanism of action since the first examples were marketed in the 1960s. The first compound in this class was carboxin, which had a narrow spectrum of useful biological activity, mainly on basidiomycetes and was used as a seed treatment. Many companies made analogues with the aim of expanding the range of species controlled and boscalid was successful in doing so.

Synthesis
The first synthesis of boscalid was disclosed in patents filed by BASF in 1995.
 * Boscalid synthesis.svg

The aminobiphenyl required for reaction with the acid chloride of 2-chloronicotinic acid is prepared in two steps. The first is a palladium-catalysed Suzuki reaction, followed by reduction. As the final product has been manufactured at the multi-tonne scale, considerable efforts have been made to optimise these reactions.

Mechanism of action
Succinate dehydrogenase inhibitors (SDHI) of this type act by binding at the quinone reduction site of the enzyme complex, preventing ubiquinone from doing so. As a consequence, the tricarboxylic acid cycle and electron transport chain cannot function.

Usage
Boscalid has fungicidal effects against a wide range of crop pests. These include Alternaria, grey mold (Botrytis cinerea), white mold (Sclerotinia sclerotiorum), and powdery mildew (Uncinula necator). As a result, it has use in crops including fruits, soybeans and vegetables. The estimated annual use of boscalid in US agriculture is mapped by the US Geological Survey and shows that it is mainly applied to fruit crops, with a maximum use of over 600000 lb in 2016. Global sales in 2014 were estimated at $390 million. The compound lacks full control of important cereal diseases, especially septoria leaf blotch Zymoseptoria tritici, which has limited its potential.

Human safety
Boscalid has low acute toxicity: the Codex Alimentarius database maintained by the FAO lists the maximum residue limits for it in various food products.

Environmental effects
The compound is very persistent in field conditions and its environmental fate and consequent ecotoxicology have been reviewed.

Resistance management
Fungal populations have the ability to develop resistance to SDHI inhibitors. This potential can be mitigated by careful management. Reports of individual pest species becoming resistant are monitored by manufacturers, regulatory bodies such as the EPA and the Fungicides Resistance Action Committee (FRAC). The risks of resistance developing can be reduced by using a mixture of two or more fungicides which each have activity on relevant pests but with unrelated mechanisms of action. FRAC assigns fungicides into classes so as to facilitate this.

Brands
Boscalid is the ISO common name for the active ingredient which is formulated into the branded product sold to end-users. It was also known as nicobifen. Endura and Emerald are the brand names first used by BASF's formulations but the compound has subsequently been sold under a range of product names.