Total synthesis of dictyodendrin B
Total synthesis of dictyodendrin B
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DOI：
10.1021/ja0541175
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发表时间：
2005-08-24
影响因子：
15
通讯作者：
Scheiper, B
中科院分区：
文献类型：
--
作者：
Fürstner, A;Domostoj, MM;Scheiper, B
本文报道了一种具有端粒酶抑制活性的稀有海洋生物碱--网枝素B（1）的全合成方法。所选路线的关键步骤是由低价钛（从TiCl 3和KC 8）介导的酮酰胺11还原环化为吲哚12，然后在Pd/C和硝基苯存在下进行光化学6π-电环化，以实现最初形成的产物的伴随脱氢/芳构化。区域选择性溴化得到的吡咯并咔唑13，然后通过锂/溴交换和淬灭得到的有机锂物种与对甲氧基苯甲醛安装在C2的侧链。将苄醇15氧化成酮17最好用催化量的四正丙基过氧化二烯铵（TPAP）和N-甲基吗啉-N-氧化物（NMO）在稀二氯甲烷溶液中进行，以避免形成过量的不对称二聚体16。通过用BCl 3选择性裂解异丙醚，借助于三氯乙基氯硫酸酯引入硫酸酯部分，所有侧甲基醚基团的脱保护，以及三氯乙基酯部分的最终还原裂解，将酮17加工成天然产物。由此形成的合成的竹荪素B的光谱数据在所有方面都与真实样品的光谱数据相匹配。此外，研究表明，吡咯并[2，3-c]咔唑13中外围−OH基团的整体脱保护伴随着自发的空气氧化，以形成dictyodendrin C的醌核心。
A concise total synthesis of dictyodendrin B (1) is reported, a scarce marine alkaloid endowed with promising telomerase inhibitory activity. Key steps of the chosen route are a reductive cyclization of ketoamide11to indole12mediated by low-valent titanium (from TiCl3and KC8) followed by a photochemical 6π-electrocyclization, which was performed in the presence of Pd/C and nitrobenzene to effect concomitant dehydrogenation/aromatization of the product initially formed. Regioselective bromination of the resulting pyrrolocarbazole13followed by lithium/bromine exchange and quenching of the resulting organolithium species withp-methoxybenzaldehyde installed the side chain at C2. Oxidation of the benzylic alcohol15thus obtained to ketone17was best achieved with catalytic amounts of tetra-n-propylammonium perruthenate (TPAP) andN-methylmorpholine-N-oxide (NMO) in dilute CH2Cl2solution to avoid the formation of undue amounts of the unsymmetrical dimer16. Ketone17was elaborated into the natural product by selective cleavage of the isopropyl ether with BCl3, introduction of the sulfate moiety with the aid of trichloroethyl chlorosulfuric acid ester, deprotection of all lateral methyl ether groups, and final reductive cleavage of the trichloroethyl ester moiety. The spectroscopic data of synthetic dictyodendrin B thus formed matched those of an authentic sample in all regards. Moreover, it was shown that global deprotection of the peripheral −OH groups in pyrrolo[2,3-c]carbazole13is accompanied by spontaneous air-oxidation to form the quinone core of dictyodendrin C.