ABSTRACT
Base-catalyzed annulation reactions of 5,6-dihydro-2(1H)-pyridones with Nazarov-type reagents are reported. The effect of the solvent polarity and the concentration of the reagents is studied. The process involves two successive Michael additions and stereoselectively provides functionalized cis-perhydroisoquinolin-1-ones.
Subject(s)
Chemistry Techniques, Synthetic , Hydrogen Peroxide/chemistry , Isoquinolines/chemistry , Catalysis , Isoquinolines/chemical synthesis , Models, Molecular , Molecular Conformation , Molecular StructureABSTRACT
The facial selectivity of double Michael addition reactions of the silylated Nazarov reagent 4 to unsaturated indolo[2,3-a]quinolizidine lactams 3 has been studied. Pentacyclic 3-H/15-H trans adducts 5 are generated from Nind -unsubstituted lactams, but the corresponding cis isomers 6 are formed when the indole nitrogen has a tert-butyloxycarbonyl (Boc) substituent. This reversal in the facial selectivity of the annulation has been rationalized by means of theoretical calculations, which indicate that the initial nucleophilic attack under stereoelectronic control is hampered by the presence of the bulky Boc group. The synthetic usefulness of the pentacyclic Nazarov-derived adducts is demonstrated by their conversion into allo and epiallo yohimbine-type targets.
ABSTRACT
After the structure originally proposed for nitraraine was shown to be incorrect by total synthesis, the alternative structure 5 was recently suggested for the alkaloid on biosynthetic grounds and by comparison with the (1)H NMR data of tangutorine. The unambiguous synthesis of 5 is reported from tryptophanol and ketodiester 6, via oxazoloquinolone lactam 7. However, the melting point and (1)H NMR data of 5 did not match those reported for the natural product.
Subject(s)
Alkaloids/chemistry , Biological Products/chemical synthesis , Carbolines/chemical synthesis , Indole Alkaloids/chemical synthesis , Lactams/chemistry , Quinolizines/chemical synthesis , Tryptophan/analogs & derivatives , Biological Products/chemistry , Carbolines/chemistry , Esters , Indole Alkaloids/chemistry , Magnetic Resonance Spectroscopy , Molecular Structure , Quinolizines/chemistry , Stereoisomerism , Tryptophan/chemistryABSTRACT
A synthetic equivalent of the Nazarov reagent, the silyl derivative 2, able to undergo base-catalyzed double Michael addition reactions with α,ß-unsaturated carbonyl compounds has been developed. The new reagent satisfactorily reacts with unsaturated indolo[2,3-a]quinolizidine lactams to give pentacyclic yohimbinone-type derivatives.
Subject(s)
Indicators and Reagents/chemistry , Indoles/chemistry , Indoles/chemical synthesis , Lactams/chemistry , Lactams/chemical synthesis , Pentanoic Acids/chemistry , Pentanoic Acids/chemical synthesis , Catalysis , Molecular Structure , StereoisomerismABSTRACT
N-[2-Methyl-5-(triazol-1-yl)phenyl]pyrimidin-2-amine derivatives were synthesized and evaluated inâ vitro for their potential use as inhibitors of Bcr-Abl. The design is based on the bioisosterism between the 1,2,3-triazole ring and the amide group. The synthesis involves a copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) as the key step, with the exclusive production of anti-(1,4)-triazole derivatives. One of the compounds obtained shows general activity similar to that of imatinib; in particular, it was observed to be more effective in decreasing the fundamental function of cdc25A phosphatases in the K-562 cell line.
