Total Synthesis of Durhamycin A

杜拉姆霉素A的全合成

• 批准号: 7805716
• 负责人: Masayuki Takahashi
• 金额: $ 4.56万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-02-16 至 2012-02-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7805716
• 关键词: Anti-HIV Agents; Antibiotics; Biological Factors; Development; Goals; Methods; Naphthalene; Naphthalenes; Oligosaccharides; Plicamycin; Property; Research; Route; Side; Staging; Validation; analog; durhamycin A; novel; public health relevance; scaffold

DESCRIPTION (provided by applicant): A strategy toward the total synthesis of durhamycin A, an aureolic acid natural product possessing potent anti-HIV properties, is described. The proposed synthesis utilizes a convergent approach to assemble the highly functionalized tricyclic aglycone, a conserved structural motif among the aureolic acids. The key steps include the [4 + 2] annulation to construct the substituted naphthalene core and the asymmetric allylation to install the polyketide side chain. The proposed synthetic route is highly amenable to analog synthesis, as it would allow late-stage installation of preassembled side chains onto a common central scaffold. Validation of this strategy would enable access to a wide range of aureolic acid analogs, potentially leading to the discovery of novel antibiotic and anti-HIV agents. PUBLIC HEALTH RELEVANCE: The proposed study on the synthesis of durhamycin A will enable access to a wide range of synthetic analogs, which will significantly enhance the discovery efforts on novel antibiotic and anti-HIV agents.

描述(由申请人提供)：描述了一种全合成硬霉素A的策略，硬霉素A是一种具有强大的抗艾滋病毒特性的金黄色天然产物。所提出的合成方法利用收敛的方法来组装高度官能化的三环苷元，这是金酸中的一个保守的结构基序。关键步骤包括[4+2]环化反应和不对称烯丙化反应，分别构筑取代的萘环和聚酮侧链。建议的合成路线高度服从模拟合成，因为它将允许将预组装的侧链安装到共同的中央支架上的后期阶段。这一战略的验证将使人们能够获得广泛的金黄色类似物，可能导致发现新的抗生素和抗艾滋病毒药物。 与公共卫生相关：拟议的关于硬霉素A合成的研究将使人们能够获得广泛的合成类似物，这将大大加强对新型抗生素和抗艾滋病毒药物的发现工作。