3 1,3,4-TRISUBSTITUTED BETA-LACTAM ANTIBIOTICS

Monobactams (2-azetidinones) are four-membered cyclic amides which exhibit very important antibacterial properties, as well as beta-lactamase- and elastase-inhibitory activities. A stereoselective asymmetric synthesis of 1,3,4-trisubstituted and 3,4-disubstituted 2-azetidinones was performed using D-glucosamine as the chiral auxiliary via a Staudinger [2+2] cycloaddition. The absolute stereochemistries at C3 and C4 of three of these potential therapeutic substances: 2-[1-{(1,3-dithian-2-yl)[2,2,2',2'-tetramethyl-4,4'-bi(1,3-dioxolan-yl)-5-yl]methyl}-2-oxo-4-(E)-styrylazetidin-3-yl]isoind-ol-1,3-dione, (1), 1-{(1,3-dithian-2-yl)[2,2,2',2'-tetrame-thyl-4,4'-bi(1,3-dioxolanyl)-5-yl]methyl}-3-methoxy-4-(E)-styrylazetidin-2-one, (2), and 3-butyl-1-{(1,3-dithian-2-yl)[2,2,2',2'-tetramethyl-4,4'-bi(1,3-dioxolan-yl)-5-yl]methyl}-4-[1-methyl-(Z)-styryl]azetidin-2-one, (3), have been established by X-ray diffraction analyses. The four-membered ring is quite planar in compounds (1) and (3), but slightly bent in (2). The arrangement of the substituents in the vicinity of the lactam ring is similar in (1) and (3), but in (2) the dithiane ring is rotated around the N1-C2' bond by approximately 120-degrees.