Concise asymmetric total synthesis of scyphostatin, a potent inhibitor of neutral sphingomyelinase |
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Authors: | Fujioka Hiromichi Sawama Yoshinari Kotoku Naoyuki Ohnaka Takuya Okitsu Takashi Murata Nobutaka Kubo Ozora Li Ruichuan Kita Yasuyuki |
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Institution: | Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, 565-0871, Japan. fujioka@phs.osaka-u.ac.jp |
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Abstract: | The concise asymmetric total synthesis of scyphostatin has been achieved by condensation of the optically active cyclohexane unit, prepared from the commercially available 1,4-cyclohexadiene by our own method, and the side chain, prepared by the method developed by Hoye and Tennakoon (T. R. Hoye, M. A. Tennakoon, Org. Lett. 2000, 2, 1481-1483). The modification of the epoxy cyclohexenone unit was achieved in a late stage of the total synthesis, and deprotection of the primary alcohol was conducted in the final step. During the synthesis several key reactions were attained: 1) intramolecular bromoetherification of the cyclohexadiene acetal; 2) stereoselective introduction of the tertiary alcohol, 3) deprotection of the acetal function to the aldehyde by combination with silyl triflate/2,4,6-collidine and the one-pot synthesis of the disilyl aldehyde compounds, with different types of silyl groups, from the dihydroxy acetal compounds; and 4) facile deprotection of the 2,4-dimethoxyphenylmethyl ((2,4)DMPM) protecting group of the primary alcohol. |
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Keywords: | asymmetric synthesis bromoetherification cyclic compounds natural products scyphostatin |
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