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石衫碱甲（１）是从中草药干层塔中提取分离到的一种高效可逆的乙酰胆碱酯酶抑制剂，经临床试验证实对老年痴呆症有显著疗效。本文报道保持石杉碱甲分子基本骨架，失二个甲基类似物７和８的合成。β－酮酯２和丙烯醛发生Ｍｉｃｈａｅｌ－Ａｌｄｏｌ反应得直立键和平伏键的羟基化合物９和１０，其相应的甲磺酸酯１１和１２分别在丙二酸钠和醋酸中１３０℃回流，直立键甲磺酸酯１１发生消去反应得需要的环内双键中间体１３，而平伏键甲磺酸酯１２则发生ＳＮ２取代反应得直立键醋酸酯１４。基于全合成路线，合成了失二碳石杉碱甲类似物７和８，其乙酰胆碱酯酶抑制活性均低于天然石杉碱甲。
Basel (1) is a kind of highly effective and reversible acetylcholinesterase inhibitor extracted from the dry layer of Chinese herbal medicine. It has been proved clinically to have a significant effect on Alzheimer’s disease. This article reports the basic skeleton of huperzine A molecule, the loss of two methyl analogs 7 and 8 synthesis. The Michael-Aldol reaction of the β-keto ester 2 with acrolein gave the hydroxyl compounds 9 and 10 of the upright and equatorial bonds, the corresponding mesylates 11 and 12 were refluxed at 130 ° C in sodium malonate and acetic acid, respectively, upright The formation of the desired double bond intermediate 13 in the mesylate 11 takes place in the elimination reaction, while the equatorial mesylate 12 undergoes an SN2 substitution reaction in the presence of the erection bond 14. Based on the full synthetic route, deasphalpin analogues 7 and 8 were synthesized and their inhibitory activities of acetylcholinesterase were lower than that of natural huperzine A.