Sahu Manas Ranjan, Ingale Sudhir R, Kontham Ravindar
Organic Chemistry Division, CSIR-National Chemical Laboratory, Dr Homi Bhabha Road, Pune-411008, India.
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad-201002, India.
Org Biomol Chem. 2025 Feb 19;23(8):1819-1822. doi: 10.1039/d4ob01970a.
We report the stereoselective total synthesis of kavaratamide A, a linear lipodepsipeptide from the cyanobacterium (collected in Kavaratti, India), and its unnatural C25-epimer. The convergent approach employs Keck asymmetric allylation to construct the chiral β-hydroxy carboxylic acid fragment [(3)-HDA; 3-hydroxydecanoic acid], while the peptide unit was assembled from L-Val, -Me-L-Ala, ()-Hiva, and ()-Pr--Me-pyr using well-orchestrated coupling methods to prevent racemization. Modifications to the Keck allylation conditions enabled the synthesis of the C25-epimer with good yield. Cytotoxicity of kavaratamide A and C25--kavaratamide A, assessed using the MTT assay, demonstrated moderate activity against HepG2 and PANC-1 cell lines.
我们报道了来自蓝藻（采集于印度卡瓦拉蒂）的线性脂环肽卡瓦拉酰胺A及其非天然C25差向异构体的立体选择性全合成。该汇聚式方法采用凯克不对称烯丙基化反应构建手性β-羟基羧酸片段[（3）-HDA；3-羟基癸酸]，而肽单元则由L-缬氨酸、-甲基-L-丙氨酸、（）-海瓦胺和（）-丙基-甲基-吡啶通过精心安排的偶联方法组装而成，以防止消旋化。对凯克烯丙基化反应条件的改进使得能够以良好的产率合成C25差向异构体。使用MTT法评估了卡瓦拉酰胺A和C25-卡瓦拉酰胺A的细胞毒性，结果表明它们对HepG2和PANC-1细胞系具有中等活性。
