ABSTRACT
The prevalence of nitrogen containing heterocycles in natural products and pharmaceuticals is a doubtless fact. In this review, recent applications of a stereoselective aza-Michael reaction as an efficient tool for the asymmetric synthesis of naturally occurring nitrogen-containing heterocyclic scaffolds and their usefulness to pharmacology are reviewed and summarized. The available data are for the first time classified according to types of heterocyclic products and subdivided in accordance with synthetic methodologies used as key stereocontrolling steps (diastereoselective or enantioselective reactions, single bond-forming or cascade reactions, etc.). This classification is convenient for organic chemists and for researchers working in the areas of natural product synthesis and medicinal chemistry. Specific attention is paid to organocatalytic asymmetric versions of the aza-Michael reaction developed over the past decade.
Subject(s)
Biological Products/chemical synthesis , Heterocyclic Compounds/chemical synthesis , Nitrogen/chemistry , Pharmaceutical Preparations/chemical synthesis , Biological Products/chemistry , Heterocyclic Compounds/chemistry , Molecular Conformation , Pharmaceutical Preparations/chemistry , StereoisomerismABSTRACT
The Nazarov reaction (cyclization) is one of the most useful synthetic tools for the stereoselective preparation of various cyclopentenone scaffolds. This review summarizes recent applications of this reaction to the synthesis of natural compounds and their usefulness to pharmacology analogs published over 2005-2016. Modern protocols for the facile generation of key cationic intermediates and efficient catalytic, in particular asymmetric, versions of Nazarov cyclization are considered. Available literature data are for the first time classified according to the chemical structures of the products, which include relatively simple non-annulated functionalized cyclopentenoids and complex polynuclear cyclopentenone derivatives annulated with one or more non-aromatic, aromatic or heteroaromatic rings. This classification is convenient for specialists in organic synthesis and for researchers working in the area of medicinal and biomolecular chemistry.
Subject(s)
Biological Products/chemistry , Biological Products/chemical synthesis , Chemistry Techniques, Synthetic/methods , Catalysis , Cyclization , StereoisomerismABSTRACT
A stereoarray isotope labeled (SAIL) lysine, (2S,3R,4R,5S,6R)-[3,4,5,6-(2)H(4);1,2,3,4,5,6-(13)C(6);2,6-(15)N(2)]lysine, was synthesized by the "head-to-tail" conversion of SAIL-Glu, (2S,3S,4R)-[3,4-(2)H(2);1,2,3,4,5-(13)C(5);2-(15)N]glutamic acid, with high stereospecificities for all five chiral centers. With the SAIL-Lys in hand, the unambiguous simultaneous stereospecific assignments were able to be established for each of the prochiral protons within the four methylene groups of the Lys side chains in proteins.
