Usami Yoshihide, Watanabe Ryo, Fujino Yuiko, Shibano Makio, Ishida Chihiro, Yoneyama Hiroki, Harusawa Shinya, Ichikawa Hayato
Laboratory of Pharmaceutical Organic Chemistry, Osaka University of Pharmaceutical Sciences, Osaka University of Pharmaceutical Sciences; 4–20–1 Nasahara, Takatsuki, Osaka 569–1094, Japan.
Chem Pharm Bull (Tokyo). 2012;60(12):1550-60. doi: 10.1248/cpb.c12-00725.
The divergent synthesis of natural withasomnines and analogues was achieved from 4-hydroxypyrazoles, which was prepared via alkaline hydrolysis of the Baeyer-Villiger oxidation products from 4-formylpyrazoles. Key steps of this synthesis are regioselective Claisen rearrangement of 4-allyloxypyrazoles and the Suzuki-Miyaura coupling of 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl trifluoromethanesulfonate and commercially available arylboronic acids. The Suzuki-Miyaura coupling at the final step of this strategy enabled facile access to natural withasomnines and their analogues. The biological activities of the twelve synthesized compounds against cyclooxygenases-1 and -2 (COX-1 and COX-2) were evaluated.
以4-羟基吡唑为原料实现了天然睡茄素及其类似物的发散合成，4-羟基吡唑是通过4-甲酰基吡唑的拜耳-维利格氧化产物的碱性水解制备的。该合成的关键步骤是4-烯丙氧基吡唑的区域选择性克莱森重排以及5,6-二氢-4H-吡咯并[1,2-b]吡唑-3-基三氟甲磺酸酯与市售芳基硼酸的铃木-宫浦偶联。该策略最后一步的铃木-宫浦偶联使得能够轻松获得天然睡茄素及其类似物。评估了十二种合成化合物对环氧化酶-1和-2（COX-1和COX-2）的生物活性。
