COPPER (I)-PROMOTED CONDENSATION OF ALPHA-AMINO-ACIDS WITH BETA-KETO THIO ESTERS - SYNTHESIS OF N-ACYLATED L-LEUCINE DERIVATIVES CONTAINING (S)-4-HYDROXY-5-METHYL-3-OXOHEXANOIC AND (S)-4-HYDROXY-2,5-DIMETHYL-3-OXOHEXANOIC ACID
COPPER (I)-PROMOTED CONDENSATION OF ALPHA-AMINO-ACIDS WITH BETA-KETO THIO ESTERS - SYNTHESIS OF N-ACYLATED L-LEUCINE DERIVATIVES CONTAINING (S)-4-HYDROXY-5-METHYL-3-OXOHEXANOIC AND (S)-4-HYDROXY-2,5-DIMETHYL-3-OXOHEXANOIC ACID
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DOI：
10.1021/jo00229a019
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发表时间：
1987-10-02
影响因子：
3.6
通讯作者：
CHOI, OS
中科院分区：
文献类型：
--
作者：
KIM, HO;OLSEN, RK;CHOI, OS
乙酸乙酯和硫代乙酸乙酯的烯醇化锂与（S）-2-羟基-3-甲基丁酸的衍生物的酰化反应，所述衍生物在羧基官能团处活化为酰氯、不对称碳酸酐或活性酯，得到相应的β-酮酯5或β-酮硫酯6.偶联α-环戊二烯基的酯衍生物氨基酸与β-碘化亚铜（I）促进酮硫代酯生成在氮上用（S）-4-羟基-5-甲基-3-氧代己酰基单元酰化的氨基酸衍生物。N-酰化亮氨酸衍生物12-15代表存在于环状缩酚肽、didemnin A、B和C中的Hip-Leu部分的2-去甲基类似物。上述方法也用于制备衍生化的Hip-Leu单元，其作为Hip C-2中心的非对映异构体的不可分离的混合物获得。
Acylation of lithium enolates of ethyl acetate and ethyl thioacetate with derivatives of (S)-2-hydroxy-3-methylbutanoic acid, activated at the carboxyl function as the acid chloride, unsymmetrical carbonic anhydride, or active ester, furnished the corresponding .beta.-keto esters 5 or .beta.-keto thio esters 6. Coupling of ester derivatives of .alpha.-amino acids to the .beta.-keto thio ester was promoted by copper(I) iodide to yield amino acid derivatives acylated at the nitrogen with an (S)-4-hydroxy-5-methyl-3-oxohexanoyl unit. N-Acylated leucine derivatives 12-15 represent 2-desmethyl analogues of the Hip-Leu moiety present in the cyclic depsipeptides, didemnins A, B, and C. The above methodology was applied also for a preparation of a derivatized Hip-Leu unit, obtained as an inseparable mixture of diastereomers at the Hip C-2 center.