Synthesis and agrochemical screening of a library of natural product-like bicyclo[2,2,2]octenones.
A general route to a series of differentially substituted bicyclo[2,2,2]octenones has been developed, making use of the in situ intramolecular Diels Alder reaction of masked ortho-benzoquinones. This approach was used to synthesize a series of thirteen key acid-containing templates from which a solution phase discovery library of 1126 diverse amides was then constructed. The rigid polycyclic nature of the templates and the prevalence of oxygenated functionality confer natural product-like qualities and three-dimensional diversity. The library was screened in HTS in vivo against a number of weed, insect and fungal model organisms leading to the discovery of a novel series of herbicidally active compounds. The development, production and biological activity of the library are described.
Smith
Stephen C
SC
Syngenta, Jealott's Hill International Research Centre, Bracknell, Berkshire RG42 6EY, UK. Steve.Smith@Syngenta.com
James
Donald R
DR
Abelman
Matthew M
MM
Sexton
Graham J
GJ
D016573:Agrochemicals / Q000138:chemical synthesis / Q000737:chemistry*; D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001688:Biological Products; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D002622:Chemistry, Agricultural / Q000379:methods; D020650:Combinatorial Chemistry Techniques; D006540:Herbicides / Q000138:chemical synthesis / Q000494:pharmacology; D007306:Insecticides / Q000138:chemical synthesis / Q000494:pharmacology; D007659:Ketones / Q000138:chemical synthesis / Q000494:pharmacology; D018716:Molecular Mimicry; D009795:Octanes / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship
D016573:Agrochemicals; D000577:Amides; D000935:Antifungal Agents; D001688:Biological Products; D001643:Bridged Bicyclo Compounds; D006540:Herbicides; D007306:Insecticides; D007659:Ketones; D009795:Octanes