Synthetic approaches to coronafacic acid, coronamic acid, and coronatine

The phytotoxin coronatine (COR) is a functional mimic of the active plant hormone (+)-7-iso-jasmonoyl-l-isoleucine (JA-IIe), which regulates stress responses. Structurally, COR is composed of a core unit, coronafacic acid (CFA), which is connected to coronamic acid (CMA), via an amide linkage. COR has been found to induce a range of biological activity in plants and based on its biological profile, COR, as well as CFA, and CMA are attractive starting points for agrochemical discovery, resulting in numerous total synthesis efforts. This review will discuss the synthetic approaches towards CFA, CMA and, ultimately COR, to date

BENO KOTRULJEVIĆ - UTEMELJITELJ HRVATSKE EKONOMSKE MISLI

Beno Kotruljević, bogati dubrovački trgovac iz prve polovine 15. stoljeća, utemeljitelj je hrvatske gospodarske misli i jedan od pionira ranog merkantilizma. Pored Juja Križanića je najznačajnije ime hrvatske ekonomske literature. Nastojeći dokazati značaj trgovine kao gospodarske djelatnosti, opisao je trgovačku praksu svog vremena i dao vlastita promišljanja o nekim bitnim pitanjima vezanim za trgovinu. U odnosu na raniju kanonističko-skolastičku gospodarsku misao, učinio je teorijske pomake u problematici trgovine, kamate, kredita i cijena. Iako je njegov rad "O trgovini i savršenom trgovcu" dosta istražen, uvijek je moguće naći u njemu nove doprinose. Ovaj rad pokušava otkriti nove spoznaje o istaknutom Dubrovčaninu

The development of natural products as phytotoxic leads for herbicide discovery

Effective agrochemicals are essential to maintaining sustainable agriculture to support a growing population. Herbicide resistance is an ever increasing problem, and in order to combat this there is a requirement for the introduction of new herbicidal agents with novel modes of action. Natural products serve as an abundant source of structurally diverse phytotoxins, which typically have novel modes of action in comparison with their synthetic counterparts. The natural product coronatine (COR), isolated from Pseudomonas syringae, has been a compound of interest to the agrochemical community since its isolation and elucidation of its phytotoxic properties. Through the industry/academia collaboration described in this thesis, coronatine is now a tractable target for a structure-activity relationship (SAR) campaign. Through the development of a scalable synthesis of the COR polyketide fragment, coronafacic acid (CFA), a diverse array of N-coronafacoyl-amino acid analogues were synthesised. The inherent flexibility of the synthesis, imparted by its convergent nature, has enabled the synthesis of several CFA analogues, featuring single point changes to the parent scaffold. In the complementary study, scalable synthesis of the COR amino acid moiety, coronamic acid (CMA), enabled diverse screening of analogues where the core moiety was varied. Through the biological evaluation of these compounds, an SAR for herbicidal activity around the COR scaffold has been identified. Initial efforts focused on modification of the amino acid component, however work in this area failed to afford any compounds of significant activity. Retention of the COR amino acid moiety, CMA, with modification of the CFA core has generated several COR analogues with good levels of potency. On analysis of this data set and supporting computational docking, we have concluded that the key convenor of potency in COR is the amino acid fragment, CMA. The CFA moiety appears to be comparatively more amenable to structural modification with the retention of potency, and we suggest that further SAR studies of the COR scaffold focus on analogues of this unit.Effective agrochemicals are essential to maintaining sustainable agriculture to support a growing population. Herbicide resistance is an ever increasing problem, and in order to combat this there is a requirement for the introduction of new herbicidal agents with novel modes of action. Natural products serve as an abundant source of structurally diverse phytotoxins, which typically have novel modes of action in comparison with their synthetic counterparts. The natural product coronatine (COR), isolated from Pseudomonas syringae, has been a compound of interest to the agrochemical community since its isolation and elucidation of its phytotoxic properties. Through the industry/academia collaboration described in this thesis, coronatine is now a tractable target for a structure-activity relationship (SAR) campaign. Through the development of a scalable synthesis of the COR polyketide fragment, coronafacic acid (CFA), a diverse array of N-coronafacoyl-amino acid analogues were synthesised. The inherent flexibility of the synthesis, imparted by its convergent nature, has enabled the synthesis of several CFA analogues, featuring single point changes to the parent scaffold. In the complementary study, scalable synthesis of the COR amino acid moiety, coronamic acid (CMA), enabled diverse screening of analogues where the core moiety was varied. Through the biological evaluation of these compounds, an SAR for herbicidal activity around the COR scaffold has been identified. Initial efforts focused on modification of the amino acid component, however work in this area failed to afford any compounds of significant activity. Retention of the COR amino acid moiety, CMA, with modification of the CFA core has generated several COR analogues with good levels of potency. On analysis of this data set and supporting computational docking, we have concluded that the key convenor of potency in COR is the amino acid fragment, CMA. The CFA moiety appears to be comparatively more amenable to structural modification with the retention of potency, and we suggest that further SAR studies of the COR scaffold focus on analogues of this unit