Synthesis of espicufolin based on 6-endo ring closure of o-alkynoylnaphthols
Synthesis of espicufolin based on 6-endo ring closure of o-alkynoylnaphthols
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基于邻炔基萘酚6-内环闭合的艾斯匹福林的合成
DOI：
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发表时间：
2001
期刊：
影响因子：
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通讯作者：
M. Sakanaka
中科院分区：
文献类型：
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作者：
H. Uno;K. Sakamoto;E. Honda;K. Fukuhara;N. Ono;Junya Tanaka;M. Sakanaka
3-乙酰氧基甲基-7-氯-5，8-二甲氧基-1-萘酚5通过DBH或I2/N-甲基吗啉进行区域选择性卤化，得到相应的2-卤代-1-萘酚8和11，它们以良好的产率转化为1-甲氧基甲氧基-3-（烷-2-炔酰氧基甲基）-2-卤代萘17和18。2-卤代萘在−78 °C与BuLi进行卤素-锂交换引发的分子内酰基转移反应以高产率得到1-甲氧基甲氧基-2-炔酰基-3-（羟甲基）萘21。在将羟甲基保护为苯甲酸酯后，通过甲氧基甲基的脱保护，随后在弱酸性条件下自发6-内环闭合，容易地形成γ-吡喃酮环。具有1-甲基丙基的吡喃酮衍生物被成功地转化为espicufolin 1。
Regioselective halogenation of 3-acetoxymethyl-7-chloro-5,8-dimethoxy-1-naphthol 5 was achieved by DBH or I2/N-methylmorpholine to give the corresponding 2-halogeno-1-naphthols 8 and 11, which were converted to 1-methoxymethoxy-3-(alk-2-ynoyloxymethyl)-2-halogenonaphthalenes 17 and 18 in good yields. An intramolecular acyl-transfer reaction of the 2-halogenonaphthalenes triggered by halogen–lithium exchange with BuLi at −78 °C gave 1-methoxymethoxy-2-alkynoyl-3-(hydroxymethyl)naphthalenes 21 in high yields. After protection of the hydroxymethyl group as a benzoate, formation of a γ-pyrone ring was easily achieved by deprotection of the methoxymethyl group followed by spontaneous 6-endo ring closure under mildly acidic conditions. The pyrone derivative having a 1-methylpropyl group was successfully converted to espicufolin 1.