Stephen G. Davies, Ai M. Fletcher, Abigail R. Hanby, Paul M. Roberts, James E. Thomson
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引用次数: 3
摘要
报道了微单蛋白612、646和680的n端α-羟基-β-氨基酸组分的不对称合成。锂(R)- n -苄基- n -(α-甲基苄基)酰胺与必需的(E)-α，β-不饱和酯缀合，然后与(−)-(樟脑磺酰基)恶氮吡啶(CSO)原位烯醇化氧化得到相应的抗α-羟基-β-氨基酯。顺序的Swern氧化和非对映选择性还原得到相应的syn-α-羟基-β-氨基酯。随后的n-去苄基化(即微ginins 612的氢解，nabro3介导的氧化n-去苄基化对微ginins 646和680的氧化n-去苄基化)和酸催化酯水解得到相应的syn-α-羟基-β-氨基酸，即微ginins 612、646和680的n端组分，收率较高。制备对映纯抗α-羟基-β-氨基酯的类似策略促进了相应的C(2)-外聚体α-羟基-β-氨基酸的不对称合成。
Asymmetric syntheses of the N-terminal α-hydroxy-β-amino acid components of microginins 612, 646 and 680
The asymmetric syntheses of the N-terminal α-hydroxy-β-amino acid components of microginins 612, 646 and 680 are reported. Conjugate addition of lithium (R)-N-benzyl-N-(α-methylbenzyl)amide to the requisite (E)-α,β-unsaturated ester followed by in situ enolate oxidation with (−)-(camphorsulfonyl)oxaziridne (CSO) gave the corresponding anti-α-hydroxy-β-amino esters. Sequential Swern oxidation followed by diastereoselective reduction gave the corresponding syn-α-hydroxy-β-amino esters. Subsequent N-debenzylation (i.e., hydrogenolysis for microginin 612, and NaBrO3-mediated oxidative N-debenzylation for microginins 646 and 680) followed by acid catalysed ester hydrolysis gave the corresponding syn-α-hydroxy-β-amino acids, the N-terminal components of microginins 612, 646 and 680, in good yield. An analogous strategy for elaboration of the enantiopure anti-α-hydroxy-β-amino esters facilitated the asymmetric synthesis of the corresponding C(2)-epimeric α-hydroxy-β-amino acids.
期刊介绍：
Cessation. Tetrahedron: Asymmetry presents experimental or theoretical research results of outstanding significance and timeliness on asymmetry in organic, inorganic, organometallic and physical chemistry, as well as its application to related disciplines, especially bio-organic chemistry.
The journal publishes critical reviews, original research articles and preliminary communications dealing with all aspects of the chemical, physical and theoretical properties of non-racemic organic and inorganic materials and processes. Topics relevant to the journal include: the physico-chemical and biological properties of enantiomers; strategies and methodologies of asymmetric synthesis; resolution; chirality recognition and enhancement; analytical techniques for assessing enantiomeric purity and the unambiguous determination of absolute configuration; and molecular graphics and modelling methods for interpreting and predicting asymmetric phenomena. Papers describing the synthesis or properties of non-racemic molecules will be required to include a separate statement in the form of a Stereochemistry Abstract, for publication in the same issue, of the criteria used for the assignment of configuration and enantiomeric purity.
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