Synthesis of Optically Active Vasicinone Based on Intramolecular Aza-Wittig Reaction and Asymmetric Oxidation(1).
Both optical isomers of a quinazoline alkaloid, vasicinone, were synthesized by two different methods. The first method used (3S)-3-hydroxy-gamma-lactam as a chiral synthon, which was, after O-TBDMS protection, o-azidobenzoylated followed by treatment with tri-n-butylphosphine to afford (S)-(-)-vasicinone via the tandem Staudinger/intramolecualr aza-Wittig reaction. The second method utilized asymmetric oxygenation of deoxyvasicinone with (1S)-(+)- or (1R)-(-)-(10-camphorsulfonyl)oxaziridine (the Davis reagent), respectively. The aza-enolate anion of deoxyvasicinone was treated with (S)-(+)-reagent to afford (R)-(+)-vasicinone in 71% ee, while the reaction with (R)-(-)-reagent gave (S)-(-)-vasicinone in 62% ee. The optical purity was analyzed by HPLC on specially modified cellulose as a stationary phase. These results provided a facile method to prepare both optical isomers of vasicinone and confirmed the recently reversed stereochemistry of natural (-)-vasicinone.
Eguchi
Shoji
S
Department of Applied Chemistry, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-01, Japan.
Suzuki
Toshio
T
Okawa
Tomohiro
T
Matsushita
Yuji
Y
Yashima
Eiji
E
Okamoto
Yoshio
Y