Synthetic Access to Noncanonical Strigolactones: Syntheses of Carlactonic Acid and Methyl Carlactonoate.

Strigolactones are plant hormones regulating essential stages of a plant's development. Their low natural abundance combined with a low chemical stability significantly hampered the detailed investigation of their biological activity. Noncanonical strigolactones lack the fused tricyclic ABC-ring system commonly present in canonical-type strigolactones but feature an open-chain unit linking structurally diverse A-ring moieties to the butenolide D-ring. We herein present an efficient synthetic access to enantiomerically pure noncanonical strigolactones by a Stille cross-coupling approach to forge the central diene moiety and demonstrate this strategy by syntheses of natural products methyl carlactonoate and carlactonic acid. Furthermore, a synthetic access to deuterium-labeled analogues of these natural products has been developed.

Synthesis of a resorcylic acid lactone (RAL) library using fluorous-mixture synthesis and profile of its selectivity against a panel of kinases.

A library of resorcylic acid lactones (RAL) containing a cis-enone moiety targeting kinases bearing a cysteine residue within the ATP-binding pocket was prepared using a fluorous-mixture synthesis and evaluated against a panel of 19 kinases thus providing important structure-activity trends. Two new analogues were then profiled for their selectivity against a panel of 402 kinases providing the broadest evaluation of this pharmacophores' selectivity.

Divergent syntheses of resorcylic acid lactones: L-783277, LL-Z1640-2, and hypothemycin.

The resorcylic acid lactones (RAL) are endowed with diverse biological activity ranging from transcription factor modulators (zearalenone and zearalenol) to HSP90 inhibitors (radicicol and pochonin D) and reversible (aigialomycin D) as well as irreversible kinase inhibitors (hypothemycin and other RAL containing a cis-enone). Our interest in broadening the diversity of this family beyond naturally occurring diversity has led us to seek a general approach that could be used to address the entire spectrum of functionalities present within this family. Herein, we present our efforts on accessing macrocycles bearing an alkane, alkene, or epoxide at the benzylic position from a common benzylic sulfide intermediate to access L-783277, LL-Z1640-2, and hypothemycin.

Simplified strigolactams as potent analogues of strigolactones for the seed germination induction of Orobanche cumana Wallr.

BACKGROUND: Strigolactones play an important role in the rhizosphere as signalling molecules stimulating the seed germination of parasitic weed seeds and hyphal branching of arbuscular micorrhiza, and also act as hormones in plant roots and shoots. Strigolactone derivatives, e.g. strigolactams, could be used as suicidal germination inducers in the absence of a host crop for the decontamination of land infested with parasitic weed seeds. RESULTS: We report the stereoselective synthesis of novel strigolactams, together with some of their critical physicochemical properties, such as water solubility, hydrolytic stability, as well as their short soil persistence. In addition, we show that such strigolactams are potent germination stimulants of O. cumana parasitic weed seeds and do not affect the seed germination and the root growth of sunflower. CONCLUSIONS: The novel strigolactam derivatives described here compare favourably with the corresponding GR-28 strigolactones in terms of biological activity and physicochemical properties. However, we believe strigolactone and strigolactam derivatives require further structural optimisation to improve their soil persistence to demonstrate a potential for agronomical applications. © 2016 Society of Chemical Industry.

Natural product biosynthesis inspired concise and stereoselective synthesis of benzopyrones and related scaffolds.

A natural product biosynthesis-inspired strategy to explore biologically relevant chemical space is presented. A phosphine-catalyzed cascade and stereoselective annulation provides a common tricyclic benzopyrone intermediate that was efficiently transformed into diverse and related naturally occurring scaffolds.