Synthesis of Simplified Tedanolide Analogues—Connecting Tedanolide to Myriaporone and Gephyronic Acid
Synthesis of Simplified Tedanolide Analogues—Connecting Tedanolide to Myriaporone and Gephyronic Acid
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简化的泰那内酯类似物的合成——将泰那内酯与 Myriaporone 和 Gephyronic Acid 连接
DOI：
10.1002/cmdc.201100576
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发表时间：
2012
期刊：
影响因子：
3.4
通讯作者：
Kalesse
中科院分区：
文献类型：
--
作者：
Muthukumar;Kalesse
1984年，Schmitz等人从加勒比海海绵Tedania ignis中分离出（+）-Tedanlide（1），[1]发现这种天然产物对KB和PS肿瘤细胞系具有皮摩尔范围的细胞毒性。重要的是，化合物1显示出显著增加植入淋巴细胞白血病的小鼠的寿命。[1]后来Fusetani等人发现了1的同源物，（+）-13-脱氧替丹诺（2）。[2]在抑制P388肿瘤生长方面表现出相似的生物学活性。[2]此外，爱尔兰[3]和McKee报告了其他代谢产物的分离，即tedanlavin C（3）和candidaspongiolides（4）。[4]在发现tedanlactone（1）的十年后，Rinehart从截形密孔藻中分离出了密孔藻酮。[5]有人提出，多胞港酮1（6）和2（11）是通过用于获得多胞港酮3/4（8/9）的分离和纯化步骤获得的人工衍生物。Myriaporones 3/4以环状半缩酮和开链异构体之间的动态平衡存在。有希望的生物活性（对L-1210鼠白血病细胞的IC 50 = 100 ng mLIPE 1）以及它们与替丹鲁肽的C10至C23部分的结构相似性（1）表明，myriaporones实际上是天然存在的类似物。myriaporones的作用模式与tedanlavone相同，其结构更简单，因此作为候选药物更具吸引力，并可作为更容易获得的潜在先导化合物的起始点。最近，一项研究证实，与tedanlavone（1）一样，myriaporones 3/4（8/9）是对真核生物具有选择性的强效蛋白质合成抑制剂。[6]从Archangium gephyra（菌株Ar 3895）的培养液中分离出类似的天然产物gephyronic acid（10）。[7a]初步生物学分析显示，选择性抑制真核蛋白质合成沿着纳摩尔细胞生长抑制作用，对一系列哺乳动物细胞系。例如，化合物10对人宫颈癌（HeLa）和人骨髓性白血病（K-562）细胞系表现出10 ng mLTA 1的IC 50值。这些相似的结构促使我们启动了一项计划，
(+)-Tedanolide (1) was isolated from the Caribbean sponge Tedania ignis by Schmitz et al. in 1984,[1] and this natural product was found to be cytotoxic against KB and PS tumor cell lines in the picomolar range. Importantly, compound 1 was shown to increase significantly the lifespan of mice implanted with lymphocytic leukaemia.[1] A congener of 1,(+)-13-deoxytedanolide (2), was discovered later by Fusetani et al.[2] from Mycale adhaerens, and it exhibited similar biological activity in inhibiting the growth of P388 tumors.[2] Furthermore, the isolation of additional metabolites, namely tedanolide C (3) and the candidaspongiolides (4) was reported by Ireland [3] and McKee.[4] Ten years after tedanolide (1) was discovered, Rinehart isolated the myriaporones from Myriapora truncate.[5] It was proposed that myriaporones 1 (6) and 2 (11) are artificial derivatives obtained through the isolation and purification steps used to obtain myriaporones 3/4 (8/9). Myriaporones 3/4 exist in dynamic equilibrium between the cyclic hemiketal and the open-chain isomer. The promising biological activity (IC50= 100 ng mLÀ1 against L-1210 murine leukemia cells) as well as the similarities of their structure to the C10 to C23 portion of tedanolide (1) suggest that the myriaporones are in fact naturally occurring analogues. The myriaporones would then share the same mode of action as tedanolide, and their simpler structure renders them more attractive as drug candidates and serves as a starting point for more readily available potential lead compounds.Recently, a study established that like tedanolide (1), myriaporones 3/4 (8/9) are potent protein synthesis inhibitors selective for eukaryotes.[6] A similar natural product, gephyronic acid (10), was isolated from the cultivation broth of Archangium gephyra (strain Ar 3895).[7a] Initial biological analysis revealed selective inhibition of eukaryotic protein synthesis along with a nanomolar cytostatic effect against a range of mammalian cell lines. For example, compound 10 exhibits an IC50 value of 10 ng mLÀ1 against human cervix carcinoma (HeLa) and human myelogenous leukemia (K-562) cell lines. These similar structures prompted us to initiate a program to identify simplified
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Gephyronic Acid 是一种来自Archangium gephyra（粘细菌）的新型真核蛋白质合成抑制剂。
DOI：
--
发表时间：
1995
期刊：
Journal of antibiotics (Tokyo. 1968)
影响因子：
--
作者：
F. Sasse;H. Steinmetz;G. Höfle;H. Reichenbach
通讯作者：
H. Reichenbach
Gephyronsäure, ein fehlendes Bindeglied zwischen Polyketid‐ Inhibitoren der eukaryotischen Proteinsynthese (Teil I): Strukturrevision und Sterechemische Zuordnung
DOI：
--
发表时间：
2011
期刊：
影响因子：
--
作者：
Lionel Nicolas;Timo Anderl;F. Sasse;H. Steinmetz;Rolf Jansen;G. Höfle;Sabine Laschat;Richard E. Taylor
通讯作者：
Richard E. Taylor
具有生物活性的海洋代谢物。
DOI：
--
发表时间：
1991
期刊：
影响因子：
--
作者：
N. Fusetani;T. Sugawara;S. Matsunaga;H. Hirota
通讯作者：
H. Hirota
DOI：
10.1271/bbb.70.161
发表时间：
2006-01
期刊：
Bioscience, Biotechnology, and Biochemistry
影响因子：
--
作者：
Kun-Hyung Lee;S. Nishimura;S. Matsunaga;N. Fusetani;H. Ichijo;S. Horinouchi;Minoru Yoshida
通讯作者：
Kun-Hyung Lee;S. Nishimura;S. Matsunaga;N. Fusetani;H. Ichijo;S. Horinouchi;Minoru Yoshida
影响因子：
3.5
作者：
Nishimura, S;Matsunaga, S;Fusetani, N
通讯作者：
Fusetani, N