Preparation of new 1,4-diazocanes as scaffolds for combinatorial chemistry
Hexahydro-2-oxo-1,4-diazocin-6-carboxylic acid constitutes a conformationally rigid, crown-shaped scaffold. An orthogonally protected (Boc at N-4 and methyl ester at 6-CO2H) representative was prepared by ring expansion of a 3-pyrrolidone-derived 1,4-diketone with MeNH2. After deprotection, this building block was further diversified by reductive aminations and amidations and by sulfonamide and urea formation. Furthermore, the 6-CO2H function was transformed into a 6-NHCbz group in one step by carboxamide degradation in the presence of BnOH. An example of a cyclic tripeptoidic structure was synthesized by amidation with N-Boc-β-alanine and glycine methyl ester. Structural features of the eight-membered heterocycle were established by single-crystal X-ray structure analysis of a 4-bromoaniline derivative.
Penning, Miriam,Christoffers, Jens
scheme or table
p. 1809 - 1818
(2012/05/04)
Enantioselective synthesis of hexahydroisobenzofuran and hexahydro-isoindole derivatives with quaternary stereocenters
Oxo esters with pyrrolidine and tetrahydrofuran rings were converted into optically active isobenzofuran and isoindole derivatives. The key step of the sequence was a copper-catalyzed asymmetric Michael reaction with methyl vinyl ketone and en-amines prepared from the oxo esters and l-valine diethylamide. The chiral auxiliary was cleaved from the products during workup and 1,5-diketones with a quaternary stereocenter are obtained with 97-99% ee. Subsequent annulation reactions were achieved in two steps via the intermediate aldol products. Georg Thieme Verlag Stuttgart - New York.
Christoffers, Jens,Sluiter, Jonas,Schmidt, Jan
experimental part
p. 895 - 900
(2011/05/07)
Total synthesis of (-)-slaframine from (2R,3S)-3-hydroxyproline
The yeast reduction products (2R,3S)-N-Boc-3-hydroxyproline esters 23 have been converted into the 3-methoxymethoxyprolinal 26 which undergoes an efficient Julia olefination with the L-serine-derived amino sulfone 29. Selective reduction of the resulting alkene 31 using diimide and cyclization leads to N-(benzyloxycarbonyl)slaframine 33c and thence to natural (-)-slaframine 5 and its more stable, crystalline N-acetyl derivative 34.
Knight, David W.,Sibley, A. William
p. 2179 - 2187
(2007/10/03)
More Articles about upstream products of 194924-95-3