Synthesis and biological activity of α,β,γ,δ-unsaturated aldehydes from diatoms
Synthesis and biological activity of α,β,γ,δ-unsaturated aldehydes from diatoms
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DOI：
10.1016/s0040-4020(03)00382-x
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发表时间：
2003-04-21
期刊：
影响因子：
2.1
通讯作者：
Pohnert, G
中科院分区：
文献类型：
--
作者：
Adolph, S;Poulet, SA;Pohnert, G
自从2，4-十碳二烯和2，4，7-十碳烯醛从硅藻Thalassiosira roula中分离出来并被鉴定为细胞抑制增殖的代谢物以来，A、β、伽马、三角洲不饱和醛受到越来越多的关注。在这种藻类和其他硅藻物种中也发现了结构上相关的α、β、伽马、三角洲不饱和醛。我们提出了这类化合物的简短和普遍的合成，以及潜在的抑制海胆卵裂的结构-活性研究。Pd-0或Co-II介导的5-碘-5-5-2，4-二烯醛与有机锌酸酯的交叉偶联使这一通用的前体可以快速而灵活地合成多种醛。在偶联过程中，保留了前驱体的双键体系的空间化学。生物测定表明，侧链的极性对抑制增殖活性很重要，与短链脂肪族同系物和具有共轭双体系的omega-oxo酸相比，2，4-十碳二烯是最具活性的化合物。相反，双键几何构型对生物活性没有影响。α，β-不饱和2E-十烯的活性也很高，而在类似链长的饱和醛的情况下活性降低。1-癸醇、2-癸酮和癸酸均不起作用。(C)2003爱思唯尔科学有限公司。保留所有权利。
a,beta,gamma,delta-Unsaturated aldehydes have gained increasing attention since 2,4-decadienal and 2,4,7-decatrienal were isolated from the diatom Thalassiosira rotula and characterized as cell antiproliferative metabolites. Structurally related alpha,beta,gamma,delta-unsaturated aldehydes were found in this alga as well as in other diatom species. We present a short and universal synthesis of this compound class along with a structure-activity study of the potential to inhibit sea urchin egg cleavage. Pd-0- or Co-II-mediated cross coupling of 5-iodo-penta-2,4-dienal with organo-zincates allows the fast and flexible synthesis of numerous aldehydes from this universal precursor. The stercochemistry of the double bond system of the precursor was preserved during the coupling. Bioassays showed that the polarity of the side chain is important for antiproliferative activity with 2,4-decadienal as the most active compound tested compared to the shorter-chain aliphatic homologues and to omega-oxo acids with conjugated double systems. In contrast, the double bond geometry has no influence on biological activity. The alpha,beta-unsaturated 2E-decenal was also highly active, while activity diminished in the case of saturated aldehydes of similar chain length. 1-Decanol, 2-decanone and decanoic acid were not active. (C) 2003 Elsevier Science Ltd. All rights reserved.