Yakushinamides, Polyoxygenated Fatty Acid Amides That Inhibit HDACs and SIRTs, from the Marine Sponge Theonella swinhoei.
Yakushinamides, Polyoxygenated Fatty Acid Amides That Inhibit HDACs and SIRTs, from the Marine Sponge Theonella swinhoei.
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DOI：
10.1021/acs.jnatprod.6b00588
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发表时间：
2016-08
影响因子：
5.1
通讯作者：
Kentaro Takada;Y. Imae;Yuji Ise;S. Ohtsuka;A. Ito;S. Okada;Minoru Yoshida;S. Matsunaga
中科院分区：
文献类型：
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作者：
Kentaro Takada;Y. Imae;Yuji Ise;S. Ohtsuka;A. Ito;S. Okada;Minoru Yoshida;S. Matsunaga
Yakushinamides A (1) 和 B (2) 是多氧脂肪酸的脯氨酰胺，已从海洋海绵 Theonella swinhoei 中分离出来，作为 HDAC 和 SIRT 的抑制剂。它们的平面结构是通过解释完整分子的 NMR 数据和甲醇分解产物的串联 FABMS 数据来确定的。为了分配 1 和 2 中三个连续的次甲基碳的相对构型，Kishi 的通用 NMR 数据库应用于甲醇分解产物。在分配 1 中分离的 1-羟基-3-甲基部分和 2 中分离的 1-羟基-2-甲基部分的相对构型期间，我们发现了诊断 NMR 特征来区分每对非对映体。 1和2的绝对构型是通过改进的Mosher方法和Marfey方法的组合来确定的。尽管改进的 Mosher 方法成功应用于 1 的甲醇分解产物，但当应用于 2 的甲醇分解产物时，该方法在 C-20 处给出了不明确的结果，即使在 C-14 和 C-15 键氧化裂解后也是如此。
Yakushinamides A (1) and B (2), prolyl amides of polyoxygenated fatty acids, have been isolated from the marine sponge Theonella swinhoei as inhibitors of HDACs and SIRTs. Their planar structures were determined by interpretation of the NMR data of the intact molecules and tandem FABMS data of the methanolysis products. For the assignment of the relative configurations of the three contiguous oxymethine carbons in 1 and 2, Kishi's universal NMR database was applied to the methanolysis products. During the assignments of relative configurations of the isolated 1-hydroxy-3-methyl moiety in 1 and the isolated 1-hydroxy-2-methyl moiety in 2, we found diagnostic NMR features to distinguish each pair of diastereomers. The absolute configurations of 1 and 2 were determined by a combination of the modified Mosher's method and Marfey's method. Although the modified Mosher's method was successfully applied to the methanolysis product of 1, this method gave an ambiguous result at C-20 when applied to the methanolysis product of 2, even after oxidative cleavage of the C-14 and C-15 bond.