含有八条环的贾多米辛:对非酶性天然产品生物合成的影响
Andrew W Robertson1, Camilo F Martinez-Farina, Deborah A Smithen
1Department of Chemistry and ⊥College of Pharmacy, Dalhousie University , Halifax, Nova Scotia B3H 4R2, Canada.
Journal of the American Chemical Society
|February 19, 2015
概括
研究人员发现了来自Streptomyces venezuelae的新型八分环含贾多米辛. 这些发现突出了通过生物合成途径探索发现新分子支架的潜力.
科学领域:
- 自然产品化学 自然产品化学
- 微生物生物合成 微生物生物合成
- 有机化学 有机化学
背景情况:
- 委内瑞拉的杆菌 (Streptomyces venezuelae) 产生各种生物活性化合物,包括贾多米辛.
- 了解自然产品的结构多样性对于药物发现至关重要.
- 在生物合成途径中探索非酶性修饰可以产生新的化学实体.
研究的目的:
- 从Streptomyces venezuelae.中分离和描述新的贾多米辛衍生物.
- 研究多胺生物合成中的结构多样性和新支架的潜力.
- 探索半合成衍生策略,以产生新的天然产品.
主要方法:
- 从Streptomyces venezuelae ISP5230.e中分离和阐明Jadomycin Oct (1) 的结构.
- 半合成衍生利用l-ornithine α-氨基基组的化学选择性化.
- 加入5-氨基瓦勒酸来合成贾多米辛AVA.
主要成果:
- 贾多米辛Oct (1) 的分离和特征,这是一个独特的八个组成的l-ornithine环,含有贾多米辛.
- 通过添加5-氨基瓦烯酸,成功合成了含有贾多米辛的另一种八个环的贾多米辛AVA.
- 通过生物合成中的非酶性步骤实现的结构多样性的证明.
结论:
- 贾多米辛Oct和贾多米辛AVA代表了贾多米辛的新型结构类.
- 这些发现强调了微生物途径产生结构多样化的天然产品的潜力.
- 这项研究以发现具有潜在治疗应用的新型分子支架为例.
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