PhthN O Cl PMP N Me N R PMP N PhthN N R PMP O PMP Me H N H2N OH R O PMP Me H H PhthN O Cl PMP N H OCH2Ph Me N PhthN OCH2Ph Me O PMP H H N H2N OH Me O PMP H H H three CH2Cl2 R = H R = Me 4 R = H R = Me H H N O PMP steps Et3N + 4 N O PMP 5 175 R = H R = Me ac O O 8 two steps N O PMP Et3N CH2Cl2 + 8b O O 207 14 15 ZNH (CO2Et)2 22 25 two steps steps three Me2 Me2 N S H3N HN O N O CO2H O SO3 – R2 O2 CNH2 H H R1 + 1 2 3 4 1¢ R1 = R2 = H R1 = Me, R2 = H R1 = H, R2 = Me R1 = R2 = Me R1 = CH2O2CNH2, R2 = H 1 a b c d 2 Carumonan 1, 2a–d† 118 J.CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 118–119 J. Chem. Research (M), 1997, 0725–0748 Simple and Condensed b-Lactams. Part 28.1 The Synthesis of C-Methylcarumonams and of a Related Bis(carbamate) J�ozsef Fetter,*a Ferenc Bertha,a M�aria Kajt�ar-Peredy,b K�aroly Lemperta and Attila S�apia aDepartment of Organic Chemistry, Technical University Budapest, H-1521 Budapest, Hungary bCentral Research Institute for Chemistry of the Hungarian Academy of Sciences, H-1525 Budapest, Hungary Racemic carumonam analogues 2a–d are synthesised and found to be devoid of any bacterial activity; NaBH4 reduction of 18 affords both epimers of 8c with the (3RS,4RS)-4-[(1RS)] epimer as the main product, and cyclocondensation of phthalimidoacetyl chloride with racemic imine 14 gives rise to the formation of (3RS,4RS)-4-[(1RS)]-15 as a single epimer.In the course of our studies into structure–activity relationships in the carumonam 12 series we have synthesised racemic C-substituted derivatives 2a–d of carumonam via key intermediates 8a–c and 25, respectively, as outlined in the Scheme. The two epimers of compound 8c were obtained by sodium tetrahydroborate reduction of acetyl derivative 185 (resulting from imine 175 on acid hydrolysis), followed by N-deacylation.As shown by X-ray molecular structure determination,13 the (3RS,4RS)-4-[(1RS)] epimer of compound 8c was formed as the main product. This is in agreement with the Felkin– Anh model14,15 of nucleophilic additions to the carbonyl group.On the other hand, cyclocondensation of phthalimidoacetyl chloride with racemic imine 14 afforded, in agreement with our expectation, the (3RS,4RS)-4-[(1RS)] compound 15 as the only epimer. Compounds 8a–c were subsequently converted by benzyloxycarbonylation into compounds 26a–c, while treatment of compound 25 with cation exchange resin Varion KS/H+ afforded compound 26d.Compounds 26a–d were converted in five steps (successive treatment with chlorosulfonyl isocyanate and aqueous NaSO3; demethoxyphenylation with CAN;8 N-sulfonation with pyridiniosulfonate, ion pair extraction9 and treatment with cation exchange resin Varion KS/Na+; debenzyloxycarbonylation by catalytic hydrogenolysis; acylation with acylating agent 3310 and de-tert-butylation) into the corresponding compounds 2a–d, none of which exhibited antibacterial activities. Techniques used: column chromatography, TLC, IR, 1H and 13C NMR, NOE, elemental analysis References: 15 Schemes: 7 *To receive any correspondence. †Compounds 2a–d are racemic, only one enantiomer shown; 2b,c have 2 epimers each.Scheme Synthesis of key intermediates 8a–c and 25. PhthN=phthalimido, PMP=4-methoxyphenyl, Z=benzyloxycarbonyl. Compounds 5, 8a–c, 14, 15 and 17 are racemic; only one enantiomer is shown. Both epimers of compound 8c have been isolated.N PhthN O Me PMP O H Me N H2N OH Me PMP O H Me H N ZNH OH R2 PMP O H Me N S N O S S N O CO2But a Racemic compounds, only one enantiomer shown. b (3 RS,4 RS)-4-[(1 RS)] epimer.c Both epimers. 18 a (3 RS,4 RS)-4-[(1 RS)]-8c a 26 3310 Me H Me CH2OH H Meb Mec H R1 H R2 H2N a b c d J. CHEM. RESEARCH (S), 1997 119 Received, 27th November 1996; Accepted, 23rd December 1996 Paper E/6/08035I References cited in this synopsis 1 Part 27, Le Thanh Giang, J. Fetter, K. Lempert, M. Kajt�ar- Peredy and A. G�om�ory, Tetrahedron, 1996, 52, 10 169. 2 M. Sendai, S. Hashiguchi, M. Tomimoto, S. Kishimoto, T. Matsuo, M. Kondo and M. Ochiai, J. Antibiot., 1985, 38, 346. 5 J. Fetter, H. V�as�arhelyi, M. Kajt�ar-Peredy, K. Lempert, J. Tam�as and G. Czira, Tetrahedron, 1995, 51, 4763. 8 D. R. Kronenthal, C. Y. Han and M. K. Taylor, J. Org. Chem., 1982, 47, 2765. 9 C. M. Cimarusti, H. E. Applegate, H. W. Chang, D. M. Floyd, W. H. Koster, W. A. Slusarchyk and M. G. Young, J. Org. Chem., 1982, 47, 179. 10 Takeda Chemical Industries, Eur. Pat. Appl., EP 93.376, 1983 (Chem. Abstr., 1984, 100, P 209.515z). 13 A. K�alm�an, personal communication. 14 M. Cerest, H. Felkin and N. Prudent, Tetrahedron Lett., 1968, 2199. 15 N. T. Anh and O. Eisenstein, Nouv. J. Chim., 1977, 1, 61; N. T. Anh, Top.