RESUMEN
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.
RESUMEN
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.
Asunto(s)
Germinación/efectos de los fármacos , Helianthus/efectos de los fármacos , Lactamas/farmacología , Orobanche/efectos de los fármacos , Helianthus/crecimiento & desarrollo , Lactamas/síntesis química , Lactamas/química , Lactonas/química , Orobanche/crecimiento & desarrollo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/crecimiento & desarrollo , Semillas/efectos de los fármacos , Semillas/crecimiento & desarrolloAsunto(s)
Productos Biológicos/química , Ciclopentanos/química , Descubrimiento de Drogas , Fármacos Neuroprotectores/química , Bibliotecas de Moléculas Pequeñas/química , Células Cultivadas , Hipocampo/efectos de los fármacos , Estructura Molecular , Neuronas/efectos de los fármacos , Bibliotecas de Moléculas Pequeñas/farmacología , EstereoisomerismoRESUMEN
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.
Asunto(s)
Benzopiranos/síntesis química , Productos Biológicos/síntesis química , Benzopiranos/metabolismo , Productos Biológicos/biosíntesis , Catálisis , Estructura Molecular , Fosfinas/química , EstereoisomerismoRESUMEN
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.
Asunto(s)
Flúor/química , Hidroxibenzoatos/química , Lactonas/síntesis química , Fosfotransferasas/metabolismo , Inhibidores de Proteínas Quinasas/síntesis química , Adenosina Trifosfato/química , Lactonas/química , Inhibidores de Proteínas Quinasas/química , Bibliotecas de Moléculas Pequeñas , Relación Estructura-ActividadRESUMEN
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.