APPROACHES TO ANALOGS OF DEHYDROGLIOTOXIN .6. EFFICIENT SYNTHESIS OF A GLIOTOXIN ANALOG WITH ANTI-REVERSE TRANSCRIPTASE ACTIVITY
APPROACHES TO ANALOGS OF DEHYDROGLIOTOXIN .6. EFFICIENT SYNTHESIS OF A GLIOTOXIN ANALOG WITH ANTI-REVERSE TRANSCRIPTASE ACTIVITY
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DOI：
10.1021/jo00883a024
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发表时间：
1976-01-01
影响因子：
3.6
通讯作者：
SPANDE, TF
中科院分区：
文献类型：
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作者：
OTTENHEIJM, HCJ;HERSCHEID, JDM;SPANDE, TF
在吲哚-2-甲酰胺上加成α-酮酰氯，然后自发地、非对映选择性地闭合成3，6-二取代二氧并哌嗪，提供了一种有效的新的合成胶质毒素类似物的方法。其中一种化合物用硫化氢处理后转化为硫代烯烃。将H_2S区域选择性和非对映选择性地加到亚甲基外基上，得到顺式二硫醇。这种锌离子催化的反应被认为是通过螯合中间体进行的。研究了顺式二硫醇转化为二硫化物的几种氧化过程。顺式二硫醇分别与SCl2和S2Cl2反应生成三硫化物和四硫化物，二硫化物用(C6H5)3P处理得到单硫化物。讨论了这种合成与已知的胶质毒素生物合成之间的相似之处。由此得到的二硫化物(总收率81%)对酶逆转录酶[Rauscher白血病病毒]具有抑制作用，其活性与胶质毒素相当。
The addition of .alpha.-ketoacyl chlorides to indolenine-2-carboxamides, followed by spontaneous, diastereoselective ring closure to 3,6-disubstituted dioxopiperazines, provides an efficient, new synthesis of gliotoxin analogues. One compound was converted into the mercaptoalkene by treatment with H2S. Regiospecific and diastereoselective addition of H2S to the exo methylene group gave cis dithiol. This Zn ion catalyzed reaction is believed to proceed via the chelate intermediate. Several oxidation procedures were studied for the conversion of the cis dithiol into disulfide. The tri- and tetrasulfides were obtained from the cis dithiol by reaction with SCl2 and S2Cl2, respectively; the monosulfide was obtained from the disulfide by treatment with (C6H5)3P. Analogies between this synthesis and what is known about the biosynthesis of gliotoxin are discussed. The disulfide thus obtained (81% overall yield) inhibited the enzyme reverse transcriptase [Rauscher leukemia virus]; its activity is comparable to that of gliotoxin.