Keywords: sullbncs of 713-alkoxycarbonyloxy-substitutcd ccphalosporanic acids tert-butyl esters, sulfcmcs of 7c~-chloro-and 7-alkylidcnc-substitutcd 3-alkoxycarbonyloxymcthylccphalosporanic acids tert-butyl esters, clastasc inhibitors.For many years the synthesis of ccphalosporin analogs containing free hydroxyl groups in positions 3 or 7 and also products of their alkylation or acylation has bccn one of the priority areas lbr the structural modification of this antibiotic. Analysis of the literature shows that cornpounds of this type arc key intermediates in reaction schemes tbr the preparation of antibacterial, anti-inflammatory, and cytotoxic substances [1][2][3][4][5][6].Thc objective of this study was to obtain new tert-butyl esters of ccphalosporanic acids containing carbonate functions at positions 7 or 3 of the ccphc,'n ring (Schemes I, 2) and to study their inhibitory properties relative to leucocyte clastasc and also their cytotoxic activity in vitro.The synthesis of sulfoncs of 7[3-alkoxycarbonyloxy-substitutcd ccphalosporanatcs 5 is shown in Scheme 1. Treatment of ester 1 with sodium borohydridc or tricthylsilanc in the presence of palladium catalyst gave 7[3-hydroxyccphalosporanatc 2. As in the case of bcnzhydryl ester of 7-oxoccphalosporinc [1], reduction of the oxo group occurred stcrcospccifically. The 7[3-configuration of the hydroxy group in compound 2, which assurncs the cis-oricntation of the protons in positions 6 and 7, was confirmed by the corresponding spin-spin coupling constant, J = 4.5 Hz.Acylation of the hydroxy group in compound 2 with 2,2,2-trichlorocthyl chlorofon'natc (3a) or di-tert-butyl pyrocarbonatc (3b) in the presence of tricthylaminc gave ccphalosporanatcs 4a,b with carbonate functional groups at position 7 accompanied by partial isomcrization of the double bond A 3 --> A 2. Oxidation of the 7-alkoxycarbonyloxy-substitutcd ccphalosporanatcs 4a,b with meta-chloropcrbcnzoic acid (MCPBA) at 0~ gave the corresponding sulfoxidcs 5a,c (n = I ) and at 20~ gave the corresponding sultbncs 5b,d (n -2). In both cases the reactions wcrc accompanied by double bond migration so that A~-ccphalosporanatcs wcrc the sole products.
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