Synthesis of novel carbopolycycles and heterocycles. 41. Synthesis of optically active vasicinone based on intramolecular aza-Wittig reaction and asymmetric oxidation
Synthesis of novel carbopolycycles and heterocycles. 41. Synthesis of optically active vasicinone based on intramolecular aza-Wittig reaction and asymmetric oxidation
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DOI：
10.1021/jo9609283
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发表时间：
1996-10-18
影响因子：
3.6
通讯作者：
Okamoto, Y
中科院分区：
文献类型：
--
作者：
Eguchi, S;Suzuki, T;Okamoto, Y
用两种不同的方法合成了喹唑啉生物碱vasicinone的两种光学异构体。第一种方法以（3S）-3-羟基-γ-内酰胺为手性合成子，经O-TBDMS保护后，邻叠氮苯甲酰化，再与三正丁基膦反应，通过串联Staudinger/分子内aza-Wittig反应得到（S）-（-）-vasicinone。第二种方法分别利用脱氧vasicinone与（1 S）-（+）-或（1 R）-（-）-（10-乙酰磺酰基）氧氮丙啶（戴维斯试剂）的不对称氧化。用（S）-（+）-试剂处理去氧洋地黄酮的氮杂烯醇阴离子，得到（R）-（+）-洋地黄酮，其ee值为71%，而与（R）-（-）-试剂反应，得到（S）-（-）-洋地黄酮，其ee值为62%。这些结果提供了一个简便的方法来制备两个光学异构体的vasicinone，并证实了最近逆转的立体化学的天然（-）-vasicinone。
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.