ABSTRACT
A modular, enantioselective approach to access the bioactive 7,9-dihydroxy- and 9-hydroxy-7-keto-8,4'-oxyneolignans is disclosed, which employs stereoselective Mitsunobu reactions of enantiopure 2-aryl-1,3-dioxan-5-ols and functionalized phenols. The enantiopure dioxanols are prepared through Sharpless asymmetric dihydroxylation of protected coniferyl or sinapyl alcohols and subsequent benzylidene acetal formation. Through a mix-and-match coupling approach, six of the eight possible erythro-7,9-dihydroxy-8,4'-oxyneolignan enantiomeric natural products (bearing a C-1' hydroxypropyl chain) were generated following sequential deprotection. Subsequent benzylic oxidation afforded the 7-keto-derivatives, resulting in enantioselective syntheses of each enantiomer of the natural products asprenol B and icariol A1.
ABSTRACT
A Zr-catalyzed synthesis of tetrasubstituted 1,3-diacylpyrroles is reported that employs the direct use of N-acyl α-aminoaldehydes with 1,3-dicarbonyl compounds. The products were formed in up to 88% yield and shown to be hydrolytically and configurationally stable under the reaction conditions (THF/1,4-dioxane and H2O). The N-acyl α-aminoaldehydes were readily prepared from the corresponding α-amino acids. The reaction tolerates a wide array of substrate types including alkyl-, aryl-, heteroaryl-, and heteroatom-containing groups on the aminoaldehyde side chain. A variety of 1,3-dicarbonyls proved amenable to the reaction along with an aldehyde derived from a l,l-dipeptide, an aldehyde generated in situ, and an N-acylated glucosamine.
