Synthesis, chromatographic resolution, and anti-human immunodeficiency virus activity of (+/-)-calanolide A and its enantiomers
Synthesis, chromatographic resolution, and anti-human immunodeficiency virus activity of (+/-)-calanolide A and its enantiomers
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DOI：
10.1021/jm950797i
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发表时间：
1996-03-15
影响因子：
7.3
通讯作者：
Xu, ZQ
中科院分区：
文献类型：
--
作者：
Flavin, MT;Rizzo, JD;Xu, ZQ
以间苯三酚[- bbb5 -> 6 -> 11 -> 18 ->(+/-)-1]为起始原料，经Pechmann反应、Friedel-Crafts酰化、4,4-二甲氧基-2-甲基丁醇铬化、环化、Luche还原等五步合成了抗hiv药物(+/-)-calanolide A(1)。在三氟乙酸和吡啶或PPTS的存在下，用乙醛缩二乙醛或三乙醛实现了铬11到铬酮18的环化。在较低温度下对铬酮18进行还原，优选得到(+/-)-1。用Kostanecki-Robinson反应从11号染色体合成的12号染色体的还原不能产生(+/-)-1。合成的(+/-)-1已被色谱分解成其旋光形式(+)-和(-)-1。合成的(+/-)-1以及合成的(+)- 1和(-)-1的抗hiv活性已经确定。只有(+)-1具有抗hiv活性，这与报道的天然产物的数据相似，而(-)-1无活性。
The anti-HIV agent (+/-)-calanolide A (1) has been synthesized in a five-step approach starting with phloroglucinol [--> 5 --> 6 --> 11 --> 18 --> (+/-)-1], which includes Pechmann reaction, Friedel-Crafts acylation, chromenylation with 4,4-dimethoxy-2-methylbutan-2-ol, cyclization, and Luche reduction. Cyclization of chromene 11 to chromanone 18 was achieved by employing either acetaldehyde diethyl acetal or paraldehyde in the presence of trifluoroacetic acid and pyridine or PPTS. Luche reduction of chromanone 18 at lower temperature preferably yielded (+/-)-1. Reduction of chromone 12, synthesized by Kostanecki-Robinson reaction from chromene 11, failed to afford (+/-)-1. The synthetic (+/-)-1 has been chromatographically resolved into its optically active forms, (+)- and (-)-1. The anti-HIV activities for synthetic (+/-)-1, as well as resultant (+)- and (-)-1, have been determined. Only (+)-1 accounted for anti-HIV activity, which was similar to the data reported for the natural product, and (-)-1 was inactive.