Eguchi Shoji, Suzuki Toshio, Okawa Tomohiro, Matsushita Yuji, Yashima Eiji, Okamoto Yoshio
Department of Applied Chemistry, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-01, Japan.
J Org Chem. 1996 Oct 18;61(21):7316-7319. doi: 10.1021/jo9609283.
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.
喹唑啉生物碱瓦西酮的两种光学异构体通过两种不同方法合成。第一种方法使用(3S)-3-羟基-γ-内酰胺作为手性合成子，在O-TBDMS保护后，用邻叠氮苯甲酰化，然后用三正丁基膦处理，通过串联施陶丁格/分子内氮杂维蒂希反应得到(S)-(-)-瓦西酮。第二种方法分别利用脱氧瓦西酮与(1S)-(+)-或(1R)-(-)-(10-樟脑磺酰基)噁唑啶（戴维斯试剂）进行不对称氧化。脱氧瓦西酮的氮杂烯醇化物阴离子用(S)-(+)-试剂处理，得到ee值为71%的(R)-(+)-瓦西酮，而与(R)-(-)-试剂反应得到ee值为62%的(S)-(-)-瓦西酮。通过以特殊改性纤维素为固定相的HPLC分析光学纯度。这些结果提供了一种制备瓦西酮两种光学异构体的简便方法，并证实了天然(-)-瓦西酮最近反转的立体化学。
