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Concise Asymmetric Total Synthesis of Scyphostatin, a Potent Inhibitor of Neutral Sphingomyelinase
Author(s) -
Fujioka Hiromichi,
Sawama Yoshinari,
Kotoku Naoyuki,
Ohnaka Takuya,
Okitsu Takashi,
Murata Nobutaka,
Kubo Ozora,
Li Ruichuan,
Kita Yasuyuki
Publication year - 2007
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200700871
Subject(s) - acetal , aldehyde , alcohol , chemistry , silylation , cyclohexane , total synthesis , intramolecular force , trifluoromethanesulfonate , aldol condensation , stereochemistry , organic chemistry , catalysis
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.