Synthetic study on nikkomycins using addition reactions of nitrones

Nikkomycin Bz是一种双肽抗生素，其n端氨基酸为γ-羟基-α-氨基酸，c端氨基酸为核苷氨基酸。1)研究了含糖助剂的α-烯丙氧羰基硝基酮。用这种方法合成了n端氨基酸片段。2) (5R)[和（5S）]-5,6-二氢-5-苯基- 2h - 1,4 -恶嗪-2- 1 n-氧化物设计合成手性(E)几何固定α-烷氧羰基瑞替酮。采用环硝酮的1,3-偶极环加成法合成了碳多毒素C的关键中间体——C端氨基酸的碳环类似物。3)探索了2-三甲基硅氧基呋喃与n -古氧基- c -烷氧基甲基-硝基酮的亲核加成反应。用该方法合成了多毒素C的关键中间体尼克霉素Bz的C端氨基酸。4)将上述方法应用于高功能化抗α-氨基酸和syn-β-取代α-氨基酸的合成。5)在MgBr_2存在下，采用(5S)-5,6-二氢-5-苯基- 2h - 1,4 -恶嗪-2- 1 n-氧化物与烯丙醇的高立体选择性环加成反应合成了抗生素氯瓦氨酸。

Nikkomycin Bz, a dipeptide antibiotic, posseses γ-hydroxy-α-amino acid as the N-terminal amino acid and a nucleoside amino acid as the C-terminal amino acid.1) α-Allyloxycarbonylnitrone having a sugar auxiliary was explored. Using this method, the N-terminal amino acid moiety was synthesized.2) (5R) [and (5S)]-5,6-Dihydro-5-phenyl-2H-1, 4-oxazin-2-one N-oxides were designed and synthesized as the chiral (E)-geometry-fixed α-alkoxycarbonylrtitrones. The key intermediate of carbocy polyoxin C, the carbocyclic analogue of the C-terminal amino acid, was synthesized by employing 1,3-dipolar cycloaddition of the cyclic nitrone.3) Nucleophilic addition reaction of 2-trimethylsilyloxyfurah to N-Gulosyi-C-alkoxymetnyl-nitrones was explored. The key intermediate of polyoxin C, the C-terminai amino acid of nikkomycin Bz, was synthesized by employing this method.4) Methods mentioned above were applied to the synthesis of highly functionalized anti- and syn-β-substituted α-amino acids.5) Highly stereoselective cycloaddition of (5S)-5,6-dihydro-5-phenyl-2H-1 ,4-oxazin-2-one N-oxide with allyll alcohol in the presence of MgBr_2 was applied to the synthesis of an antibiotic clavalanine.