Bu 3 SnH-mediated aryl radical cyclisation of enamide 9 proceeded in a 6-endo-trig manner to give exclusively tetrahydroisoquinoline derivative 12, whereas enamide 10b having a (Z)-phenylthio group at the terminus of the Nvinylic bond gave exclusively the 5-exo-trig cyclisation product 16.

Enamides 5, on treatment with Bu(3)SnH-AIBN, underwent aryl radical cyclization in a 5-exo manner to give 1-[bis(phenylthio)methyl]dihydroisoindoles 6, which were partially desulfurized with Bu(3)SnH-AIBN to give 1-mono(phenylthio)methyl congeners 7. Formation of 6 from 5 may be explained by the presence of two phenylthio groups at the terminus of the N-vinylic bond of 5, since enamide 8a having no phenylthio group underwent aryl radical cyclization in a 6-endo manner. Compound 7d (R = CF(3)) was transformed into sulfoxide 16, which was treated with (CF(3)CO)(2)O and then with 10% NaOH to give a model compound 20 of mappicine ketone (MPK) (1) through aldol condensation of aldehyde 18. An attempt to synthesize MPK using this method with sulfoxide 28 prepared from 25, however, was unsuccessful, and, instead, photochemical cyclization of enamide 38 prepared from 25 furnished MPK.

Novel oxazolidinone analogues bearing a condensed heteroaromatic ring as the C-ring substructure were synthesized as candidate antibacterial agents. Analogues 16 and 21 bearing imidazo[1,2-a]pyridine and 18 and 23 bearing [1,2,4]triazolo[1,5-a]pyridine as the C-ring had excellent in vitro antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecalis (VRE), and penicillin-resistant Streptococcus pneumoniae (PRSP). They also showed promising therapeutic effects in a mouse model of lethal infection. Preliminary safety data (inhibitory effects on cytochrome P450 isoforms and monoamine oxidases) were satisfactory. Further evaluation of 18 and 23 is ongoing.

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