School of Chemistry, The University of Sydney, NSW 2006, Australia.
Chemistry. 2011 Nov 25;17(48):13544-52. doi: 10.1002/chem.201102538. Epub 2011 Oct 18.
The total synthesis and stereochemical assignment of gallinamide A, an antimalarial depsipeptide of cyanobacterial origin, is described. Synthesis of the four possible N-terminal diastereoisomers of gallinamide A (including the natural product symplostatin 4) was achieved using a divergent strategy from a common imide fragment. The natural product and corresponding diastereoisomers were synthesized in 30-33% overall yield in a longest linear sequence of 8 steps. Comparative NMR spectroscopic studies of the four synthetic diastereoisomers with the isolated natural product demonstrated that gallinamide A possesses a dimethylated L-isoleucyl residue at the N-terminus. As such, we have shown that gallinamide A is structurally and stereochemically identical to symplostatin 4. Gallinamide A and its N-terminal diastereoisomers were also shown to possess significant antimalarial activity with IC(50) values in the nanomolar range against the 3D7 strain of Plasmodium falciparum.
描述了来源于蓝藻的抗疟深海鞘氨醇肽 gallinamide A 的全合成及立体化学结构确定。采用发散策略从一个共同的酰亚胺片段合成了 gallinamide A 的四个可能的 N-端非对映异构体（包括天然产物 symplostatin 4）。天然产物及其相应的非对映异构体以最长线性序列 8 步合成，总收率为 30-33%。对四个合成的非对映异构体与分离的天然产物的比较 NMR 谱学研究表明，gallinamide A 在 N-末端具有二甲基化的 L-异亮氨酸残基。因此，我们已经表明 gallinamide A 在结构和立体化学上与 symplostatin 4 相同。Gallinamide A 及其 N-端非对映异构体也表现出显著的抗疟活性，对 Plasmodium falciparum 的 3D7 株的 IC（50）值在纳摩尔范围内。
