Synthesis and in vitro cytotoxic evaluation of spiro-β-lactone-γ-lactam scaffolds

Strategies and methodologies for the construction of spiro-γ-lactams: an update

“…Recently, a similar ring-closing metathesis was applied in the synthesis of spiro-β-lactone lactams starting from D-and L-xylose-derived isothiocyanates (Scheme 13). 18 Treatment of isothiocyanate 59 derived from D-xylose with bis(n-tributyltin) oxide (TBTO) afforded amine 60 which was converted into the sugar-derived vinyl acrylamide 62 by acylation with methacryloyl chloride (61). Subsequent ring-closing metathesis in the presence of Grubbs II afforded unsaturated spirocyclic -lactam 63 in 89% yield.…”

“…The proposed mechanistic pathway includes the generation of an aryl/alkyl sulfonyl radical, selective addition of the radical to the alkyne moiety and subsequent ipso-cyclization to afford the dearomatized products. Moreover, 18 O-isotope labelling experiments demonstrated that oxygen atom in the generated C−O double bond is derived from H2O. Soon after, the same research group reported the synthesis of 3-sulfonyl-spiro--lactams from N-substituted propiolamides using anilines and DABSO as aryl sulfonyl radical sources, and Eosin Y as the photocatalyst.…”