Total synthesis and allelopathic activity of cytosporones A-C

Abstract

A busca por herbicidas eficientes e ambientalmente corretos tem sido foco de numerosos estudos sobre a síntese de compostos isolados de fontes naturais. Citosporonas, as quais são lipídeos fenólicos isolados de fungos, apresentam notáveis propriedades biológicas. Este artigo relata a preparação das citosporonas A, B e C, através de uma rota sintética curta e com excelentes rendimentos. Os compostos sintetizados foram avaliados quanto às suas atividades alelopáticas em sementes de alface (Lactuca sativa L). Citosporona A e seu precursor metilado mostraram notável atividade alelopática, inibindo a germinação de sementes e crescimento das plântulas.The search for efficient, environmentally friendly herbicides has been the focus of numerous studies on the organic synthesis of compounds isolated from natural sources. Cytosporones, which are phenolic lipids isolated from fungi, exhibit noteworthy biological properties. This paper reports the preparation of cytosporones A-C from the same starting material through a short synthetic route, with good yields. All compounds were tested for allelopathic activity on lettuce (Lactuca sativa L) seeds. Cytosporone A and its methylated precursor showed remarkable allelopathic activity, inhibiting seed germination and plantule growth.

A novel cytosporone 3-Heptyl-4,6-dihydroxy-3H-isobenzofuran-1-one: synthesis; toxicological, apoptotic and immunomodulatory properties; and potentiation of mutagenic damage

“…Agonist binding to the receptor leads to the activation of receptor-related specific genes that control apoptosis and metabolic regulation [ 41 ]. According to Liu [ 14 ], the pharmacophoric components necessary for binding to Nur77 include the hydroxybenzene ring and the hydrophobic acyl chain, whereas the key element for the activation of the biological function of Nur77 is an ester group.…”

“…Apoptosis is characterized by cell shrinkage, chromatin condensation, and the activation of specific cysteine proteases, known as caspases [ 1 ]. Other authors have demonstrated the apoptotic activity of compounds similar to AMS049 [ 2 , 14 , 16 , 41 , 52 – 54 ], suggesting the induction of apoptosis by the activation of Nur77 [ 55 , 56 ].…”

“…Lin [ 58 ] suggested that AMS049 analogs such as cytosporone B reduce the mitochondrial membrane potential. In addition, critical events of apoptosis such as the cleavage of caspase-9 and caspase-3 are induced [ 14 ]. As discussed earlier, this is added to the activation of Nur77, which is possibly the result of the presence of an ester radical in the structure of these compounds.…”

“…The amphiphilic property of these compounds, which is attributed to the presence of non-isoprenoid side chains bound to the hydroxybenzene ring, permits their interaction with the lipid bilayer [ 4 – 6 ], the formation of liposomes [ 7 ], protection against oxidative stress [ 8 ] and the inhibition of bacterial [ 9 – 11 ] and tumor cell growth [ 12 , 13 ]. Particularly interesting are phenolic lipids of the cytosporone class, which present allelopathic activity [ 14 ] and can interact with the orphan nuclear receptor Nur77, triggering apoptosis [ 15 ]. This observation is supported by a study from our research group showing that the synthetic resorcinolic lipid 3-heptyl-3,4,6-trimethoxy-3 H -isobenzofuran-1-one (AMS35AA) has anti-genotoxic and immunostimulatory activities, potentiates the mutagenic effect of the chemotherapy drug cyclophosphamide and increases the rate of apoptosis induced by this drug [ 2 ].…”

An Efficient Synthesis of Cytosporone B

“…Dong 等 [12] 利用铑催化的乙烯基氢酰化反应, 从已知化 合物出发经过 3 步以 50.2%的收率得到 Csn-B. 我们前 期的路线 [4] 和 Beatriz 课题组 [13] [14,15] . Willgerodt-Kindler 重 排反应由于操作简便, 而且可以进行克级甚至公斤级的 制备而广泛应用于医药工业 [16] 9), 在该过 程中吗啡啉既是反应试剂又是反应溶剂.…”