latrunculins

latrunculins
  • 文章类型: Journal Article
    Latcruculins是在细胞生物学中用于阻断肌动蛋白聚合的海洋毒素。因此,开发新的合成策略和合成方法对于提高合成策略和方法非常重要,调节或控制这种生物学价值。文献中发现的全部合成都针对类似的断开连接,特别是涉及复发性4-乙酰基-1,3-噻唑烷-2-酮伴侣的羟醛策略。在这里,我们描述了另一种断开和随后的立体选择性转换,以构建适合于latrunculin和类似物合成的立体定向。从(+)-β-香茅烯开始。关键的立体选择性转化涉及不对称的Krische烯丙基化,在1,5-反立体控制下的羟醛反应,和Tishchenko-Evans减少伴随着特殊的酯置换,允许安装天然产品的关键立体中心。
    Latrunculins are marine toxins used in cell biology to block actin polymerization. The development of new synthetic strategies and methods for their synthesis is thus important in order to improve, modulate or control this biological value. The total syntheses found in the literature all target similar disconnections, especially an aldol strategy involving a recurrent 4-acetyl-1,3-thiazolidin-2-one ketone partner. Herein, we describe an alternative disconnection and subsequent stereoselective transformations to construct a stereopentade amenable to latrunculin and analogue synthesis, starting from (+)-β-citronellene. Key stereoselective transformations involve an asymmetric Krische allylation, an aldol reaction under 1,5-anti stereocontrol, and a Tishchenko-Evans reduction accompanied by a peculiar ester transposition, allowing to install key stereogenic centers of the natural products.
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  • 文章类型: Journal Article
    由青光眼引起的不可逆视力丧失的负担持续上升。虽然对疾病的发病机制还没有很好的了解,眼内压(IOP)是预防青光眼性视力丧失的唯一可改变的危险因素.在大多数成人青光眼中,医学管理仍然是治疗的第一线,并且青光眼的医学治疗的发展遵循指数曲线。这篇综述跟踪了近年来新药物和药物输送系统的快速发展。从目前使用的抗青光眼药物中引入具有全新作用机制的Rho激酶抑制剂已经是一个重要的里程碑。拉坦前列汀Bunod是一部小说,单分子,提供两种活性代谢物,通过两种不同的途径降低眼内压。比马前列素植入物和曲伏前列素泪点塞试图缓解青光眼患者的慢性药物使用。纳米技术是一种不断发展的药物输送途径。大麻素在青光眼的医疗管理中的作用仍然模棱两可。对眼压的短期影响,对患者神经认知健康产生耐受性和副作用的风险大大超过了潜在的益处.对LatrunculinB的研究,腺苷受体激动剂,特定基因沉默和干细胞疗法有望对青光眼治疗产生影响。虽然有一些证据支持溴莫尼定在神经保护中的作用,需要进一步的研究来阐明美金刚和神经营养因子的作用.从膳食补充α硫辛酸中获益的证据,Forskolin,银杏是有限的。
    The burden of irreversible vision loss from Glaucoma continues to rise. While the disease pathogenesis is not well understood, intraocular pressure (IOP) is the only modifiable risk factor identified to prevent glaucomatous vision loss. Medical management remains the first-line of treatment in most adult glaucomas and the evolution of medical therapy for glaucoma has followed an exponential curve. This review tracks the rapid development of new medications and drug delivery systems in the recent years. Introduction of Rho kinase inhibitors with an entirely new mechanism of action from that of the currently used anti glaucoma medications has been a significant milestone. Latanoprostene Bunod is a novel, single molecule which provides two active metabolites that work through two different pathways for reducing intra ocular pressure. Bimatoprost implants and travoprost punctum plugs attempt to ease chronic medication use in glaucoma patients. Nanotechnology is an evolving route of drug delivery. Role of cannabinoids in medical management of glaucoma remain equivocal. The relatively short term effect on IOP, the risks of developing tolerance and side effects impacting patients\' neurocognitive health greatly outweigh the potential benefit. Research on Latrunculin B, Adenosine receptor agonists, Specific gene silencing and Stem cell therapy are poised to make an impact on glaucoma treatment. While there is some evidence to support the role of Brimonidine in neuroprotection, further research is needed to clarify the role of Memantine and Neurotrophins. Evidence for benefit from dietary supplementation with Alpha lipoic acid, Forskolin , and Ginko Biloba is limited.
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