Synthesis of a Library of “Lead-Like” γ‑Lactams by a One Pot, Four-Component Reaction

The synthesis of a pilot scale library of 116 structurally diverse γ-lactams is reported. The library core structure emanates from a γ-lactam forming one-pot, four-component reaction of ammonium acetate, <i>p-</i>methoxythiophenol, <i>p-</i>methoxybenzaldehyde, and maleic anhydride. Structural diversity then arises from amide coupling, thioaryl cleavage, <i>N-</i>functionalization, and heterocycle forming reactions on this core structure. Computational analysis reveals that the library contains molecular properties and shape diversity suitable for drug lead and biological probe discovery

Synthesis of 6,6′-Binaphthopyran-2-one Natural Products: Pigmentosin A, Talaroderxines A and B

Efficient and stereoselective syntheses of pigmentosin A, talaroderxine A, and its diastereomer talaroderxine B are reported. The binaphthyl ring system is assembled by vanadium-catalyzed phenolic coupling of tricyclic precursors. These key intermediates were prepared by Michael–Dieckmann annulation of a protected orsellinate ester, with the requisite pyranones accessed by a new variant of Ghosez’s sulfone-epoxide annulation. Preliminary biological experiments are reported for pigmentosin

Diastereoselective Base-Catalyzed Formal [4 + 2] Cycloadditions of <i>N</i>‑Sulfonyl Imines and Cyclic Anhydrides

A diastereoselective base-catalyzed Mannich reaction of cyclic, enolizable anhydrides and <i>N</i>-sulfonyl imines for the synthesis of δ-lactams is reported. This anhydride Mannich reaction tolerates imines derived from aryl and enolizable aldehydes. A base-catalyzed product epimerization pathway ensures high anti diastereoselectivity in aryl and achiral enolizable imines

Diastereoselective Synthesis of γ- and δ‑Lactams from Imines and Sulfone-Substituted Anhydrides

Sulfone-substituted γ- and δ-lactams have been prepared in a single step with high diastereoselectivity. Sulfonylglutaric anhydrides produce intermediates that readily decarboxylate to provide δ-lactams with high diastereoselectivity. Substituents at the 3- or 4-position of the glutaric anhydride induce high levels of stereocontrol. Sulfonylsuccinic anhydrides produce intermediate carboxylic acids that can be trapped as methyl esters or allowed to decarboxylate under mild conditions. This method has been applied to a short synthesis of the pyrrolizidine alkaloid (±)-isoretronecanol