556

556.2, found 556.3; [M?+?HCOO]?calcd. to high nanomolar range. + Nfor C22H29N3O5S [M?+?H]+ calcd. 448.2, found 448.3; [M?+?Na]+ calcd. 470.2, found 470.3; [M?+?HCOO] ? calcd. 492.2 found 492.3. 2.2.2. Benzyl (R)-(4-(methylthio)-1-oxo-1-((4-sulphamoylphenethyl)amino)butan-2-yl)carbamate (2) White solid (88%); mp 173C174?C; 1H-NMR (300?MHz, DMSO-d6): 8.04 (t, 1H, N+ Nfor C21H27N3O5S2 [M?+?H]+ calcd. 466.2 found 466.3; [M?+?Na]+ calcd. 488.1, found 488.3; [M?+?HCOO]? calcd. 510.1 found 510.2. 2.2.3. Benzyl (R)-(3-methyl-1-oxo-1-((4-sulphamoylphenethyl)amino)butan-2-yl)carbamate (3) White solid (95%); mp 185C186?C; 1H-NMR (300?MHz, DMSO-d6): 8.05 (t, 1H, N+ OCONfor C21H27N3O5S [M?+?H]+ calcd. 434.2, found 434.3; [M?+?Na]+ calcd. 456.2, found 456.3; [M?+?HCOO]? calcd. 478.2, found 478.3. 2.2.4. Benzyl (S)-(1-oxo-3-(phenylthio)-1-((4-sulphamoylphenethyl)amino)propan-2-yl)carbamate (4) White solid (85%); mp 117C118?C; 1H-NMR (300?MHz, DMSO-d6): 8.25 (t, 2H, N+ Nfor C25H27N3O5S2 [M?+?H]+ calcd. 514.2, found 514.3; [M?+?Na]+ calcd. 536.2, found 456.3; [M?+?HCOO]? calcd. 558.2, found 558.2. 2.2.5. tert-Butyl (R)-(1-oxo-1-((4-sulphamoylphenethyl)amino)propan-2-yl)carbamate (5) White solid (90%); mp 165C166?C; 1H-NMR (300?MHz, DMSO-d6): 7.88 (t, 1H, Nfor C16H25N3O5S [M?+?Na]+ calcd. 394.2, found 394.2; [M?+?HCOO]? calcd. 416.2, found 416.1; [M-H]? calcd. 370.2, found 370.1. 2.2.6. (9H-fluoren-9-yl)methyl (2-oxo-2-((4-sulphamoylphenethyl)amino)ethyl)carbamate (6) White colored solid (91%); mp 134C135?C; 1H-NMR (300?MHz, DMSO-d6): 7.97 (t, 1H, N+ Nfor C25H25N3O5S [M?+?H]+ calcd. 480.2, found 480.3; [M?+?NH4]+ calcd. 497.2, found 497.3; [M?+?HCOO]? calcd. 524,2 discovered 524.2. 2.2.7. (9H-fluoren-9-yl)methyl (S)-(1-oxo-3-phenyl-1-((4-sulphamoylphenethyl)amino)propan-2-yl)carbamate (7) White colored solid (93%); mp 174C175?C; 1H-NMR (300?MHz, DMSO-d6): 8.15 (t, 1H, N+ OCON+ Nfor C32H31N3O5S [M?+?H]+ calcd. 592.2, found 592.4; [M?+?Na]+ calcd. 570.2, found 570.4; [M?+?HCOO]? calcd. 614.2, found 614.3. 2.2.8. Benzyl (R)-(3-(1H-indol-3-yl)-1-oxo-1-((4-sulphamoylphenethyl)amino)propan-2-yl)carbamate (8) White solid (88%); mp 194C195?C; 1H-NMR (400?MHz, DMSO-d6): 10.82 (s, 1H, Indole-N+ Nfor C27H28N4O5S [M?+?H]+ calcd. 521.2, found 521.3; [M-H]? calcd. 519.2, found 519.2. 2.2.9. tert-Butyl (S)-(4-(methylthio)-1-oxo-1-((4-sulphamoylphenethyl)amino)butan-2-yl)carbamate (9) White solid (89%); mp 172C173?C; 1H-NMR (400?MHz, DMSO-d6): 7.94 (t, 1H, Nfor C18H29N3O5S [M?+?Na]+ calcd. 454.1, found 454.3; [M?+?HCOO]? calcd. 476.2, found 476.2. 2.2.10. tert-Butyl (R)-(3-methyl-1-oxo-1-((4-sulphamoylphenethyl)amino)butan-2-yl)carbamate (10) White solid (90%); mp 160C161?C; 1H-NMR (400?MHz, DMSO-d6): 8.02 (t, 1H, Nfor C18H29N3O5S [M?+?Na]+ calcd. 422.2, found 422.3; [M?+?HCOO]? calcd. 444.2, found 444.2. 2.2.11. tert-Butyl ((2R,3R)-3-methyl-1-oxo-1-((4-sulphamoylphenethyl)amino)pentan-2-yl)carbamate (11) White solid (91%); mp 191C192?C; 1H-NMR (400?MHz, DMSO-d6): 7.98 (t, 1H, N+ CHCH(CH3)Cfor C19H31N3O5S [M?+?Na]+ calcd. 436.2, found 436.3; [M-H]? calcd. 412.2, found 412.2; [M?+?HCOO]?calcd. 458.2, found 458.2. 2.2.12. Benzyl (R)-(1,4-dioxo-1,4-bis((4-sulphamoylphenethyl)amino)butan-2-yl)carbamate (12) White solid (73%); mp 249C250?C; 1H-NMR (400?MHz, DMSO-d6): 8.02 (t, 1H, N+ N+ NHCH2Cfor C28H33N5O8S2 [M?+?H]+ calcd. 632.2, found 632.4; [M-H]? calcd. KJ Pyr 9 630.2, found 630.3. 2.3. General process of the formation of amino acidCsulphonamide conjugates, 13C24 N-protected aminoacylbenzotriazole (1.0 equiv.), (4-sulphamoylphenyl)methanaminium chloride (1.0 equiv.), and Et3N (2.5 equiv.) had been put through microwave irradiation (100?W, 70?C) in DCM (5?ml) for 30?min. After conclusion of the response (monitoring TLC dish), all volatiles had been eliminated by rotavapour as well as the acquired crude item was crystallised from ethanol. 2.3.1. Benzyl (R)-(4-methyl-1-oxo-1-((4-sulphamoylbenzyl)amino)pentan-2-yl)carbamate (13) White solid (74%); mp 173C174?C; 1H-NMR (300?MHz, DMSO-d6): 8.60 (t, 1H, CON+ Nfor C21H27N3O5S [M?+?H]+ calcd. 434.2, found 434.3[M?+?Na]+ calcd. 466.2, found 466.3; [M?+?HCOO]? calcd. 478.2, found 478.2. 2.3.2. Benzyl (R)-(4-(methylthio)-1-oxo-1-((4-sulphamoylbenzyl)amino)butan-2-yl)carbamate (14) White solid (80%); mp 167C168?C; 1H-NMR (300?MHz, DMSO-d6): 8.59 (t, 1H, CON+ Nfor C20H25N3O5S2 [M?+?H]+ calcd. 452.1, found 452.2; [M?+?HCOO]? calcd. 496.2, found 496.2. 2.3.3. Benzyl (R)-(3-methyl-1-oxo-1-((4-sulphamoylbenzyl)amino)butan-2-yl)carbamate (15) White solid (89%); mp 141C142?C; 1H-NMR (300?MHz, DMSO-d6): 8.58 (t, 1H, CON+ OCONfor C20H25N3O5S [M?+?H]+ calcd. 420.2, found 420.2; [M?+?Na]+ calcd. 442.1, found 442.3; [M?+?HCOO]?calcd. 464.2, found 464.2. 2.3.4. Benzyl (S)-(1-oxo-3-(phenylthio)-1-((4-sulphamoylbenzyl)amino)propan-2-yl)carbamate (16) White solid (72%); mp 196C197?C; 1H-NMR (300?MHz, DMSO-d6): 8.76 (t, 2H, CON+ OCONfor C24H25N3O5S2 [M?+?H]+ calcd. 500.1, found 500.3; [M?+?HCOO]? calcd. 544.1, found 544.2. 2.3.5. tert-Butyl (2-oxo-2-((4-sulphamoylbenzyl)amino)ethyl)carbamate (17) White colored solid (70%); mp 172C173?C; 1H-NMR (300?MHz, DMSO-d6): 8.41 (t, 1H, CONfor C14H21N3O5S [M?+?Na]+ calcd. 366.1, found 366.1; [M-H]? calcd. 342.1, found 342.1; [M?+?HCOO]? calcd. 388.1, found 388.1. 2.3.6. tert-Butyl (R)-(1-oxo-1-((4-sulphamoylbenzyl)amino)propan-2-yl)carbamate (18) White solid (85%); mp 197C198?C; 1H-NMR (300?MHz, DMSO-d6): 8.42 (t, 1H, CONfor C15H23N3O5S [M?+?Na]+ calcd. 380.1, found 380.2; [M-H]? calcd. 356.1, found 356.1; [M?+?HCOO]? calcd. 402.1, found 402.1. 2.3.7. tert-Butyl (R)-(1-oxo-3-phenyl-1-((4-sulphamoylbenzyl)amino)propan-2-yl)carbamate (19) White solid (95%); mp 198C199?C; 1H-NMR (300?MHz, DMSO-d6): 8.55 (t, 1H, CON+ Nfor C21H27N3O5S [M?+?Na]+ calcd. 456.2, found 456.2; AXIN2 [M?+?HCOO]? calcd. 478.2, found 478.2. 2.3.8. (9H-fluoren-9-yl)methyl (S)-(1-oxo-3-phenyl-1-((4-sulphamoylbenzyl)amino)propan-2-yl)carbamate (20) White colored solid (88%); mp 221C222?C; 1H-NMR (300?MHz, DMSO-d6): 8.64 (t, 1H, CON+ Nfor C31H29N3O5S [M?+?Na]+ calcd. 556.2, found 556.3; [M?+?HCOO]?calcd. 600.2, found 600.2. 2.3.9. tert-Butyl (R)-(4-(methylthio)-1-oxo-1-((4-sulphamoylbenzyl)amino)butan-2-yl)carbamate (21) White solid (85%); mp 142C143?C; 1H-NMR (400?MHz, DMSO-d6): 8.48 (t, 1H, CONfor C17H27N3O5S2 [M?+?Na]+ calcd. 440.1, found 440.2; [M-H]? calcd. 416.1, found 416.2; [M?+?HCOO]? calcd. 462.1, found 462.2. 2.3.10. tert-Butyl (R)-(3-methyl-1-oxo-1-((4-sulphamoylbenzyl)amino)butan-2-yl)carbamate (22) White solid (87%); mp 163C164?C; 1H-NMR (400?MHz, DMSO-d6): 8.49 (t, 1H, CONfor C17H27N3O5S [M?+?Na]+ calcd. 408.2, found 408.2; [M-H]? calcd. 384.2, found 384.2; [M?+?HCOO]? calcd. 430.2, found 430.2. 2.3.11. Benzyl (R)-(3-(1H-indol-3-yl)-1-oxo-1-((4-sulphamoylbenzyl)amino)propan-2-yl)carbamate (23) White solid.452.1, found 452.2; [M?+?HCOO]? calcd. 1H-NMR (300?MHz, DMSO-d6): 8.04 (t, 1H, N+ Nfor C21H27N3O5S2 [M?+?H]+ calcd. 466.2 found 466.3; [M?+?Na]+ calcd. 488.1, found 488.3; [M?+?HCOO]? calcd. 510.1 found 510.2. 2.2.3. Benzyl (R)-(3-methyl-1-oxo-1-((4-sulphamoylphenethyl)amino)butan-2-yl)carbamate (3) White solid (95%); mp 185C186?C; 1H-NMR (300?MHz, DMSO-d6): 8.05 (t, 1H, N+ OCONfor C21H27N3O5S [M?+?H]+ calcd. 434.2, found 434.3; [M?+?Na]+ calcd. 456.2, found 456.3; [M?+?HCOO]? calcd. 478.2, found 478.3. 2.2.4. Benzyl (S)-(1-oxo-3-(phenylthio)-1-((4-sulphamoylphenethyl)amino)propan-2-yl)carbamate (4) White solid (85%); mp 117C118?C; 1H-NMR (300?MHz, DMSO-d6): 8.25 (t, 2H, N+ Nfor C25H27N3O5S2 [M?+?H]+ calcd. 514.2, found 514.3; [M?+?Na]+ calcd. 536.2, found 456.3; [M?+?HCOO]? calcd. 558.2, found 558.2. 2.2.5. tert-Butyl (R)-(1-oxo-1-((4-sulphamoylphenethyl)amino)propan-2-yl)carbamate (5) White solid (90%); mp 165C166?C; 1H-NMR (300?MHz, DMSO-d6): 7.88 (t, 1H, Nfor C16H25N3O5S [M?+?Na]+ calcd. 394.2, found 394.2; [M?+?HCOO]? calcd. 416.2, found 416.1; [M-H]? calcd. 370.2, found 370.1. 2.2.6. (9H-fluoren-9-yl)methyl (2-oxo-2-((4-sulphamoylphenethyl)amino)ethyl)carbamate (6) White colored solid (91%); mp 134C135?C; 1H-NMR (300?MHz, DMSO-d6): 7.97 (t, 1H, N+ Nfor C25H25N3O5S [M?+?H]+ calcd. 480.2, found 480.3; [M?+?NH4]+ calcd. 497.2, found 497.3; [M?+?HCOO]? calcd. 524,2 discovered 524.2. 2.2.7. (9H-fluoren-9-yl)methyl (S)-(1-oxo-3-phenyl-1-((4-sulphamoylphenethyl)amino)propan-2-yl)carbamate (7) White colored solid (93%); mp 174C175?C; 1H-NMR (300?MHz, DMSO-d6): 8.15 (t, 1H, N+ OCON+ Nfor C32H31N3O5S [M?+?H]+ calcd. 592.2, found 592.4; [M?+?Na]+ calcd. 570.2, found 570.4; [M?+?HCOO]? calcd. 614.2, found 614.3. 2.2.8. Benzyl (R)-(3-(1H-indol-3-yl)-1-oxo-1-((4-sulphamoylphenethyl)amino)propan-2-yl)carbamate (8) White solid (88%); mp 194C195?C; 1H-NMR (400?MHz, DMSO-d6): 10.82 (s, 1H, Indole-N+ Nfor C27H28N4O5S [M?+?H]+ calcd. 521.2, found 521.3; [M-H]? calcd. 519.2, found 519.2. 2.2.9. tert-Butyl (S)-(4-(methylthio)-1-oxo-1-((4-sulphamoylphenethyl)amino)butan-2-yl)carbamate (9) White solid (89%); mp 172C173?C; 1H-NMR (400?MHz, DMSO-d6): 7.94 (t, 1H, Nfor C18H29N3O5S [M?+?Na]+ calcd. 454.1, found 454.3; [M?+?HCOO]? calcd. 476.2, found 476.2. 2.2.10. tert-Butyl (R)-(3-methyl-1-oxo-1-((4-sulphamoylphenethyl)amino)butan-2-yl)carbamate (10) White solid (90%); mp 160C161?C; 1H-NMR (400?MHz, DMSO-d6): 8.02 (t, 1H, Nfor C18H29N3O5S [M?+?Na]+ calcd. 422.2, found 422.3; [M?+?HCOO]? calcd. 444.2, found 444.2. 2.2.11. tert-Butyl ((2R,3R)-3-methyl-1-oxo-1-((4-sulphamoylphenethyl)amino)pentan-2-yl)carbamate (11) White solid (91%); mp 191C192?C; 1H-NMR (400?MHz, DMSO-d6): 7.98 (t, 1H, N+ CHCH(CH3)Cfor C19H31N3O5S [M?+?Na]+ calcd. 436.2, found 436.3; [M-H]? calcd. 412.2, found 412.2; [M?+?HCOO]?calcd. 458.2, found 458.2. 2.2.12. Benzyl (R)-(1,4-dioxo-1,4-bis((4-sulphamoylphenethyl)amino)butan-2-yl)carbamate (12) White solid (73%); mp 249C250?C; 1H-NMR (400?MHz, DMSO-d6): 8.02 (t, 1H, N+ N+ NHCH2Cfor C28H33N5O8S2 [M?+?H]+ calcd. 632.2, found 632.4; [M-H]? calcd. 630.2, found 630.3. 2.3. General process of the formation of amino acidCsulphonamide conjugates, 13C24 N-protected aminoacylbenzotriazole (1.0 equiv.), (4-sulphamoylphenyl)methanaminium chloride (1.0 equiv.), and Et3N (2.5 equiv.) had been put through microwave irradiation (100?W, 70?C) in DCM (5?ml) for 30?min. After conclusion of the response (monitoring TLC dish), all volatiles had been eliminated by rotavapour as well as the acquired crude item was crystallised from ethanol. 2.3.1. Benzyl (R)-(4-methyl-1-oxo-1-((4-sulphamoylbenzyl)amino)pentan-2-yl)carbamate (13) White solid (74%); mp 173C174?C; 1H-NMR (300?MHz, DMSO-d6): 8.60 (t, 1H, CON+ Nfor C21H27N3O5S [M?+?H]+ calcd. 434.2, found 434.3[M?+?Na]+ calcd. 466.2, found 466.3; [M?+?HCOO]? calcd. 478.2, found 478.2. 2.3.2. Benzyl (R)-(4-(methylthio)-1-oxo-1-((4-sulphamoylbenzyl)amino)butan-2-yl)carbamate (14) White solid (80%); mp 167C168?C; 1H-NMR (300?MHz, DMSO-d6): 8.59 (t, 1H, CON+ Nfor C20H25N3O5S2 [M?+?H]+ calcd. 452.1, found 452.2; [M?+?HCOO]? calcd. 496.2, found 496.2. 2.3.3. Benzyl (R)-(3-methyl-1-oxo-1-((4-sulphamoylbenzyl)amino)butan-2-yl)carbamate (15) White solid (89%); mp 141C142?C; 1H-NMR (300?MHz, DMSO-d6): 8.58 (t, 1H, CON+ OCONfor C20H25N3O5S [M?+?H]+ calcd. 420.2, found 420.2; [M?+?Na]+ calcd. 442.1, found 442.3; [M?+?HCOO]?calcd. 464.2, found 464.2. 2.3.4. Benzyl (S)-(1-oxo-3-(phenylthio)-1-((4-sulphamoylbenzyl)amino)propan-2-yl)carbamate (16) White solid (72%); mp 196C197?C; 1H-NMR (300?MHz, DMSO-d6): 8.76 (t, 2H, CON+ OCONfor C24H25N3O5S2 [M?+?H]+ calcd. 500.1, found 500.3; [M?+?HCOO]? calcd. 544.1, found 544.2. 2.3.5. tert-Butyl (2-oxo-2-((4-sulphamoylbenzyl)amino)ethyl)carbamate (17) White colored solid (70%); mp 172C173?C; 1H-NMR (300?MHz, DMSO-d6): 8.41 (t, 1H, CONfor C14H21N3O5S [M?+?Na]+ calcd. 366.1, found 366.1; [M-H]? calcd. 342.1, found 342.1; [M?+?HCOO]? calcd. 388.1, found 388.1. 2.3.6. tert-Butyl (R)-(1-oxo-1-((4-sulphamoylbenzyl)amino)propan-2-yl)carbamate (18) White solid (85%); mp 197C198?C; 1H-NMR (300?MHz, DMSO-d6): 8.42 (t, 1H, CONfor C15H23N3O5S [M?+?Na]+ calcd. 380.1, found 380.2; [M-H]? calcd. 356.1, found 356.1; [M?+?HCOO]? calcd. 402.1, found 402.1. 2.3.7. tert-Butyl (R)-(1-oxo-3-phenyl-1-((4-sulphamoylbenzyl)amino)propan-2-yl)carbamate (19) White solid (95%); mp 198C199?C; 1H-NMR (300?MHz, DMSO-d6): 8.55 (t, 1H, CON+ Nfor C21H27N3O5S [M?+?Na]+ calcd. 456.2, KJ Pyr 9 found 456.2; [M?+?HCOO]? calcd. 478.2, found 478.2. 2.3.8. (9H-fluoren-9-yl)methyl (S)-(1-oxo-3-phenyl-1-((4-sulphamoylbenzyl)amino)propan-2-yl)carbamate (20) White colored solid (88%); mp 221C222?C; 1H-NMR (300?MHz, DMSO-d6): 8.64 (t, 1H, CON+ Nfor C31H29N3O5S [M?+?Na]+ calcd. 556.2, found 556.3; [M?+?HCOO]?calcd. 600.2, found 600.2..442.1, found 442.3; [M?+?HCOO]?calcd. 1H, N+ Nfor C21H27N3O5S2 [M?+?H]+ calcd. 466.2 found 466.3; [M?+?Na]+ calcd. 488.1, found 488.3; [M?+?HCOO]? calcd. 510.1 found 510.2. 2.2.3. Benzyl (R)-(3-methyl-1-oxo-1-((4-sulphamoylphenethyl)amino)butan-2-yl)carbamate (3) White solid (95%); mp 185C186?C; 1H-NMR (300?MHz, DMSO-d6): 8.05 (t, 1H, N+ OCONfor C21H27N3O5S [M?+?H]+ calcd. 434.2, found 434.3; [M?+?Na]+ calcd. 456.2, found 456.3; [M?+?HCOO]? calcd. 478.2, found 478.3. 2.2.4. Benzyl (S)-(1-oxo-3-(phenylthio)-1-((4-sulphamoylphenethyl)amino)propan-2-yl)carbamate (4) White solid (85%); mp 117C118?C; 1H-NMR (300?MHz, DMSO-d6): 8.25 (t, 2H, N+ Nfor C25H27N3O5S2 [M?+?H]+ calcd. 514.2, found 514.3; [M?+?Na]+ calcd. 536.2, found 456.3; [M?+?HCOO]? calcd. 558.2, found 558.2. 2.2.5. tert-Butyl (R)-(1-oxo-1-((4-sulphamoylphenethyl)amino)propan-2-yl)carbamate (5) White solid (90%); mp 165C166?C; 1H-NMR (300?MHz, DMSO-d6): 7.88 (t, 1H, Nfor C16H25N3O5S [M?+?Na]+ calcd. 394.2, found 394.2; [M?+?HCOO]? calcd. 416.2, found 416.1; [M-H]? calcd. 370.2, found 370.1. 2.2.6. (9H-fluoren-9-yl)methyl (2-oxo-2-((4-sulphamoylphenethyl)amino)ethyl)carbamate (6) White colored solid (91%); mp 134C135?C; 1H-NMR (300?MHz, DMSO-d6): 7.97 (t, 1H, N+ Nfor C25H25N3O5S [M?+?H]+ calcd. 480.2, found 480.3; [M?+?NH4]+ calcd. 497.2, found 497.3; [M?+?HCOO]? calcd. 524,2 discovered 524.2. 2.2.7. (9H-fluoren-9-yl)methyl (S)-(1-oxo-3-phenyl-1-((4-sulphamoylphenethyl)amino)propan-2-yl)carbamate (7) White colored solid (93%); mp 174C175?C; 1H-NMR (300?MHz, DMSO-d6): 8.15 (t, 1H, N+ OCON+ Nfor C32H31N3O5S [M?+?H]+ calcd. 592.2, found 592.4; [M?+?Na]+ calcd. 570.2, found 570.4; [M?+?HCOO]? calcd. 614.2, found 614.3. 2.2.8. Benzyl (R)-(3-(1H-indol-3-yl)-1-oxo-1-((4-sulphamoylphenethyl)amino)propan-2-yl)carbamate (8) White solid (88%); mp 194C195?C; 1H-NMR (400?MHz, DMSO-d6): 10.82 (s, 1H, Indole-N+ Nfor C27H28N4O5S [M?+?H]+ calcd. 521.2, found 521.3; [M-H]? calcd. 519.2, found 519.2. 2.2.9. tert-Butyl (S)-(4-(methylthio)-1-oxo-1-((4-sulphamoylphenethyl)amino)butan-2-yl)carbamate (9) White solid (89%); mp 172C173?C; 1H-NMR (400?MHz, DMSO-d6): 7.94 (t, 1H, Nfor C18H29N3O5S [M?+?Na]+ calcd. 454.1, found 454.3; [M?+?HCOO]? calcd. 476.2, found 476.2. 2.2.10. tert-Butyl (R)-(3-methyl-1-oxo-1-((4-sulphamoylphenethyl)amino)butan-2-yl)carbamate (10) White solid (90%); mp 160C161?C; 1H-NMR (400?MHz, DMSO-d6): 8.02 (t, 1H, Nfor C18H29N3O5S [M?+?Na]+ calcd. 422.2, found 422.3; [M?+?HCOO]? calcd. 444.2, found 444.2. 2.2.11. tert-Butyl ((2R,3R)-3-methyl-1-oxo-1-((4-sulphamoylphenethyl)amino)pentan-2-yl)carbamate (11) White solid (91%); mp 191C192?C; 1H-NMR (400?MHz, DMSO-d6): 7.98 (t, 1H, N+ CHCH(CH3)Cfor C19H31N3O5S [M?+?Na]+ calcd. 436.2, found 436.3; [M-H]? calcd. 412.2, found 412.2; [M?+?HCOO]?calcd. 458.2, found 458.2. 2.2.12. Benzyl (R)-(1,4-dioxo-1,4-bis((4-sulphamoylphenethyl)amino)butan-2-yl)carbamate (12) White solid (73%); mp 249C250?C; 1H-NMR (400?MHz, DMSO-d6): 8.02 (t, 1H, N+ N+ NHCH2Cfor C28H33N5O8S2 [M?+?H]+ calcd. 632.2, found 632.4; [M-H]? calcd. 630.2, found 630.3. 2.3. General process of the formation of amino acidCsulphonamide conjugates, 13C24 N-protected aminoacylbenzotriazole (1.0 equiv.), (4-sulphamoylphenyl)methanaminium chloride (1.0 equiv.), and Et3N (2.5 equiv.) had been put through microwave irradiation (100?W, 70?C) in DCM (5?ml) for 30?min. After conclusion of the response (monitoring TLC dish), all volatiles had been eliminated by rotavapour as well as the acquired crude item was crystallised from ethanol. 2.3.1. Benzyl (R)-(4-methyl-1-oxo-1-((4-sulphamoylbenzyl)amino)pentan-2-yl)carbamate (13) White solid (74%); mp 173C174?C; 1H-NMR (300?MHz, DMSO-d6): 8.60 (t, 1H, CON+ Nfor C21H27N3O5S [M?+?H]+ calcd. 434.2, found 434.3[M?+?Na]+ calcd. 466.2, found 466.3; [M?+?HCOO]? calcd. 478.2, found 478.2. 2.3.2. Benzyl (R)-(4-(methylthio)-1-oxo-1-((4-sulphamoylbenzyl)amino)butan-2-yl)carbamate (14) White solid (80%); mp 167C168?C; 1H-NMR (300?MHz, DMSO-d6): 8.59 (t, 1H, CON+ Nfor C20H25N3O5S2 [M?+?H]+ calcd. 452.1, found 452.2; [M?+?HCOO]? calcd. 496.2, found 496.2. 2.3.3. Benzyl (R)-(3-methyl-1-oxo-1-((4-sulphamoylbenzyl)amino)butan-2-yl)carbamate (15) White solid (89%); mp 141C142?C; 1H-NMR (300?MHz, DMSO-d6): 8.58 (t, 1H, CON+ OCONfor C20H25N3O5S [M?+?H]+ calcd. 420.2, found 420.2; [M?+?Na]+ calcd. 442.1, found 442.3; [M?+?HCOO]?calcd. 464.2, found 464.2. 2.3.4. Benzyl (S)-(1-oxo-3-(phenylthio)-1-((4-sulphamoylbenzyl)amino)propan-2-yl)carbamate (16) White solid (72%); mp 196C197?C; 1H-NMR (300?MHz, DMSO-d6): 8.76 (t, 2H, CON+ OCONfor C24H25N3O5S2 [M?+?H]+ calcd. 500.1, found 500.3; [M?+?HCOO]? calcd. 544.1, found 544.2. 2.3.5. tert-Butyl (2-oxo-2-((4-sulphamoylbenzyl)amino)ethyl)carbamate (17) White colored solid (70%); mp 172C173?C; 1H-NMR (300?MHz, DMSO-d6): 8.41 (t, 1H, CONfor C14H21N3O5S [M?+?Na]+ calcd. 366.1, found 366.1; [M-H]? calcd. 342.1, found 342.1; [M?+?HCOO]? calcd. 388.1, found 388.1. 2.3.6. tert-Butyl (R)-(1-oxo-1-((4-sulphamoylbenzyl)amino)propan-2-yl)carbamate (18) White solid (85%); mp 197C198?C; 1H-NMR (300?MHz, DMSO-d6): 8.42 (t, 1H, CONfor C15H23N3O5S [M?+?Na]+ calcd. 380.1, found 380.2; [M-H]? calcd. 356.1, found 356.1; [M?+?HCOO]? calcd..Benzyl (R)-(3-methyl-1-oxo-1-((4-sulphamoylbenzyl)amino)butan-2-yl)carbamate (15) White colored stable (89%); mp 141C142?C; 1H-NMR (300?MHz, DMSO-d6): 8.58 (t, 1H, CON+ OCONfor C20H25N3O5S [M?+?H]+ calcd. with activity from the reduced to high nanomolar range. + Nfor C22H29N3O5S [M?+?H]+ calcd. 448.2, found 448.3; [M?+?Na]+ calcd. 470.2, found 470.3; [M?+?HCOO] ? calcd. 492.2 found 492.3. 2.2.2. Benzyl (R)-(4-(methylthio)-1-oxo-1-((4-sulphamoylphenethyl)amino)butan-2-yl)carbamate (2) White solid (88%); mp 173C174?C; 1H-NMR (300?MHz, DMSO-d6): 8.04 (t, 1H, N+ Nfor C21H27N3O5S2 [M?+?H]+ calcd. 466.2 found 466.3; [M?+?Na]+ calcd. 488.1, found 488.3; [M?+?HCOO]? calcd. 510.1 found 510.2. 2.2.3. Benzyl (R)-(3-methyl-1-oxo-1-((4-sulphamoylphenethyl)amino)butan-2-yl)carbamate (3) White solid (95%); mp 185C186?C; 1H-NMR (300?MHz, DMSO-d6): 8.05 (t, 1H, N+ OCONfor C21H27N3O5S [M?+?H]+ calcd. 434.2, found 434.3; [M?+?Na]+ calcd. 456.2, found 456.3; [M?+?HCOO]? calcd. 478.2, found 478.3. 2.2.4. Benzyl (S)-(1-oxo-3-(phenylthio)-1-((4-sulphamoylphenethyl)amino)propan-2-yl)carbamate (4) White solid (85%); mp 117C118?C; 1H-NMR (300?MHz, DMSO-d6): 8.25 (t, 2H, N+ Nfor C25H27N3O5S2 KJ Pyr 9 [M?+?H]+ calcd. 514.2, found 514.3; [M?+?Na]+ calcd. 536.2, found 456.3; [M?+?HCOO]? calcd. 558.2, found 558.2. 2.2.5. tert-Butyl (R)-(1-oxo-1-((4-sulphamoylphenethyl)amino)propan-2-yl)carbamate (5) White solid (90%); mp 165C166?C; 1H-NMR (300?MHz, DMSO-d6): 7.88 (t, 1H, Nfor C16H25N3O5S [M?+?Na]+ calcd. 394.2, found 394.2; [M?+?HCOO]? calcd. 416.2, found 416.1; [M-H]? calcd. 370.2, found 370.1. 2.2.6. (9H-fluoren-9-yl)methyl (2-oxo-2-((4-sulphamoylphenethyl)amino)ethyl)carbamate (6) White colored solid (91%); mp 134C135?C; 1H-NMR (300?MHz, DMSO-d6): 7.97 (t, 1H, N+ Nfor C25H25N3O5S [M?+?H]+ calcd. 480.2, found 480.3; [M?+?NH4]+ calcd. 497.2, found 497.3; [M?+?HCOO]? calcd. 524,2 discovered 524.2. 2.2.7. (9H-fluoren-9-yl)methyl (S)-(1-oxo-3-phenyl-1-((4-sulphamoylphenethyl)amino)propan-2-yl)carbamate (7) White colored solid (93%); mp 174C175?C; 1H-NMR (300?MHz, DMSO-d6): 8.15 (t, 1H, N+ OCON+ Nfor C32H31N3O5S [M?+?H]+ calcd. 592.2, found 592.4; [M?+?Na]+ calcd. 570.2, found 570.4; [M?+?HCOO]? calcd. 614.2, found 614.3. 2.2.8. Benzyl (R)-(3-(1H-indol-3-yl)-1-oxo-1-((4-sulphamoylphenethyl)amino)propan-2-yl)carbamate (8) White solid (88%); mp 194C195?C; 1H-NMR (400?MHz, DMSO-d6): 10.82 (s, 1H, Indole-N+ Nfor KJ Pyr 9 C27H28N4O5S [M?+?H]+ calcd. 521.2, found 521.3; [M-H]? calcd. 519.2, found 519.2. 2.2.9. tert-Butyl (S)-(4-(methylthio)-1-oxo-1-((4-sulphamoylphenethyl)amino)butan-2-yl)carbamate (9) White solid (89%); mp 172C173?C; 1H-NMR (400?MHz, DMSO-d6): 7.94 (t, 1H, Nfor C18H29N3O5S [M?+?Na]+ calcd. 454.1, found 454.3; [M?+?HCOO]? calcd. 476.2, found 476.2. 2.2.10. tert-Butyl (R)-(3-methyl-1-oxo-1-((4-sulphamoylphenethyl)amino)butan-2-yl)carbamate (10) White solid (90%); mp 160C161?C; 1H-NMR (400?MHz, DMSO-d6): 8.02 (t, 1H, Nfor C18H29N3O5S [M?+?Na]+ calcd. 422.2, found 422.3; [M?+?HCOO]? calcd. 444.2, found 444.2. 2.2.11. tert-Butyl ((2R,3R)-3-methyl-1-oxo-1-((4-sulphamoylphenethyl)amino)pentan-2-yl)carbamate (11) White solid (91%); mp 191C192?C; 1H-NMR (400?MHz, DMSO-d6): 7.98 (t, 1H, N+ CHCH(CH3)Cfor C19H31N3O5S [M?+?Na]+ calcd. 436.2, found 436.3; [M-H]? calcd. 412.2, found 412.2; [M?+?HCOO]?calcd. 458.2, found 458.2. 2.2.12. Benzyl (R)-(1,4-dioxo-1,4-bis((4-sulphamoylphenethyl)amino)butan-2-yl)carbamate (12) White solid (73%); mp 249C250?C; 1H-NMR (400?MHz, DMSO-d6): 8.02 (t, 1H, N+ N+ NHCH2Cfor C28H33N5O8S2 [M?+?H]+ calcd. 632.2, found 632.4; [M-H]? calcd. 630.2, found 630.3. 2.3. General process of the formation of amino acidCsulphonamide conjugates, 13C24 N-protected aminoacylbenzotriazole (1.0 equiv.), (4-sulphamoylphenyl)methanaminium chloride (1.0 equiv.), and Et3N (2.5 equiv.) had been put through microwave irradiation (100?W, 70?C) in DCM (5?ml) for 30?min. After conclusion of the response (monitoring TLC dish), all volatiles had been eliminated by rotavapour as well as the acquired crude item was crystallised from ethanol. 2.3.1. Benzyl (R)-(4-methyl-1-oxo-1-((4-sulphamoylbenzyl)amino)pentan-2-yl)carbamate (13) White solid (74%); mp 173C174?C; 1H-NMR (300?MHz, DMSO-d6): 8.60 (t, 1H, CON+ Nfor C21H27N3O5S [M?+?H]+ calcd. 434.2, found 434.3[M?+?Na]+ calcd. 466.2, found 466.3; [M?+?HCOO]? calcd. 478.2, found 478.2. 2.3.2. Benzyl (R)-(4-(methylthio)-1-oxo-1-((4-sulphamoylbenzyl)amino)butan-2-yl)carbamate (14) White solid (80%); mp 167C168?C; 1H-NMR (300?MHz, DMSO-d6): 8.59 (t, 1H, CON+ Nfor C20H25N3O5S2 [M?+?H]+ calcd. 452.1, found 452.2; [M?+?HCOO]? calcd. 496.2, found 496.2. 2.3.3. Benzyl (R)-(3-methyl-1-oxo-1-((4-sulphamoylbenzyl)amino)butan-2-yl)carbamate (15) White solid (89%); mp 141C142?C; 1H-NMR (300?MHz, DMSO-d6): 8.58 (t, 1H, CON+ OCONfor C20H25N3O5S [M?+?H]+ calcd. 420.2, found 420.2; [M?+?Na]+ calcd. 442.1, found 442.3; [M?+?HCOO]?calcd. 464.2, found 464.2. 2.3.4. Benzyl (S)-(1-oxo-3-(phenylthio)-1-((4-sulphamoylbenzyl)amino)propan-2-yl)carbamate (16) White solid (72%); mp 196C197?C; 1H-NMR (300?MHz, DMSO-d6): 8.76 (t, 2H, CON+ OCONfor C24H25N3O5S2 [M?+?H]+ calcd. 500.1, found 500.3; [M?+?HCOO]? calcd. 544.1, found 544.2. 2.3.5. tert-Butyl (2-oxo-2-((4-sulphamoylbenzyl)amino)ethyl)carbamate (17) White colored solid (70%); mp 172C173?C; 1H-NMR (300?MHz, DMSO-d6): 8.41 (t, 1H, CONfor C14H21N3O5S [M?+?Na]+ calcd. 366.1, found 366.1; [M-H]? calcd. 342.1, found 342.1; [M?+?HCOO]? calcd. 388.1, found 388.1. 2.3.6. tert-Butyl (R)-(1-oxo-1-((4-sulphamoylbenzyl)amino)propan-2-yl)carbamate (18) White solid (85%); mp 197C198?C; 1H-NMR (300?MHz, DMSO-d6): 8.42 (t, 1H, CONfor C15H23N3O5S [M?+?Na]+ calcd. 380.1, found 380.2; [M-H]? calcd. 356.1, found 356.1; [M?+?HCOO]? calcd. 402.1, found 402.1. 2.3.7. tert-Butyl (R)-(1-oxo-3-phenyl-1-((4-sulphamoylbenzyl)amino)propan-2-yl)carbamate (19) White solid (95%); mp 198C199?C; 1H-NMR (300?MHz, DMSO-d6): 8.55 (t, 1H, CON+ Nfor C21H27N3O5S [M?+?Na]+ calcd. 456.2, found 456.2; [M?+?HCOO]? calcd. 478.2, found 478.2. 2.3.8. (9H-fluoren-9-yl)methyl (S)-(1-oxo-3-phenyl-1-((4-sulphamoylbenzyl)amino)propan-2-yl)carbamate (20) White colored solid (88%); mp 221C222?C; 1H-NMR (300?MHz, DMSO-d6): 8.64 (t, 1H, CON+ Nfor C31H29N3O5S [M?+?Na]+ calcd. 556.2, found 556.3; [M?+?HCOO]?calcd. 600.2, found 600.2. 2.3.9. tert-Butyl (R)-(4-(methylthio)-1-oxo-1-((4-sulphamoylbenzyl)amino)butan-2-yl)carbamate (21) White solid (85%);.416.1, found 416.2; [M?+?HCOO]? calcd. effective inhibitors of hCA I, hCA VA, and hCA XII, with activity from the reduced to high nanomolar range. + Nfor C22H29N3O5S [M?+?H]+ calcd. 448.2, found 448.3; [M?+?Na]+ calcd. 470.2, found 470.3; [M?+?HCOO] ? calcd. 492.2 found 492.3. 2.2.2. Benzyl (R)-(4-(methylthio)-1-oxo-1-((4-sulphamoylphenethyl)amino)butan-2-yl)carbamate (2) White solid (88%); mp 173C174?C; 1H-NMR (300?MHz, DMSO-d6): 8.04 (t, 1H, N+ Nfor C21H27N3O5S2 [M?+?H]+ calcd. 466.2 found 466.3; [M?+?Na]+ calcd. 488.1, found 488.3; [M?+?HCOO]? calcd. 510.1 found 510.2. 2.2.3. Benzyl (R)-(3-methyl-1-oxo-1-((4-sulphamoylphenethyl)amino)butan-2-yl)carbamate (3) White solid (95%); mp 185C186?C; 1H-NMR (300?MHz, DMSO-d6): 8.05 (t, 1H, N+ OCONfor C21H27N3O5S [M?+?H]+ calcd. 434.2, found 434.3; [M?+?Na]+ calcd. 456.2, found 456.3; [M?+?HCOO]? calcd. 478.2, found 478.3. 2.2.4. Benzyl (S)-(1-oxo-3-(phenylthio)-1-((4-sulphamoylphenethyl)amino)propan-2-yl)carbamate (4) White solid (85%); mp 117C118?C; 1H-NMR (300?MHz, DMSO-d6): 8.25 (t, 2H, N+ Nfor C25H27N3O5S2 [M?+?H]+ calcd. 514.2, found 514.3; [M?+?Na]+ calcd. 536.2, found 456.3; [M?+?HCOO]? calcd. 558.2, found 558.2. 2.2.5. tert-Butyl (R)-(1-oxo-1-((4-sulphamoylphenethyl)amino)propan-2-yl)carbamate (5) White solid (90%); mp 165C166?C; 1H-NMR (300?MHz, DMSO-d6): 7.88 (t, 1H, Nfor C16H25N3O5S [M?+?Na]+ calcd. 394.2, found 394.2; [M?+?HCOO]? calcd. 416.2, found 416.1; [M-H]? calcd. 370.2, found 370.1. 2.2.6. (9H-fluoren-9-yl)methyl (2-oxo-2-((4-sulphamoylphenethyl)amino)ethyl)carbamate (6) White colored solid (91%); mp 134C135?C; 1H-NMR (300?MHz, DMSO-d6): 7.97 (t, 1H, N+ Nfor C25H25N3O5S [M?+?H]+ calcd. 480.2, found 480.3; [M?+?NH4]+ calcd. 497.2, found 497.3; [M?+?HCOO]? calcd. 524,2 discovered 524.2. 2.2.7. (9H-fluoren-9-yl)methyl (S)-(1-oxo-3-phenyl-1-((4-sulphamoylphenethyl)amino)propan-2-yl)carbamate (7) White colored solid (93%); mp 174C175?C; 1H-NMR (300?MHz, DMSO-d6): 8.15 (t, 1H, N+ OCON+ Nfor C32H31N3O5S [M?+?H]+ calcd. 592.2, found 592.4; [M?+?Na]+ calcd. 570.2, found 570.4; [M?+?HCOO]? calcd. 614.2, found 614.3. 2.2.8. Benzyl (R)-(3-(1H-indol-3-yl)-1-oxo-1-((4-sulphamoylphenethyl)amino)propan-2-yl)carbamate (8) White solid (88%); mp 194C195?C; 1H-NMR (400?MHz, DMSO-d6): 10.82 (s, 1H, Indole-N+ Nfor C27H28N4O5S [M?+?H]+ calcd. 521.2, found 521.3; [M-H]? calcd. 519.2, found 519.2. 2.2.9. tert-Butyl (S)-(4-(methylthio)-1-oxo-1-((4-sulphamoylphenethyl)amino)butan-2-yl)carbamate (9) White solid (89%); mp 172C173?C; 1H-NMR (400?MHz, DMSO-d6): 7.94 (t, 1H, Nfor C18H29N3O5S [M?+?Na]+ calcd. 454.1, found 454.3; [M?+?HCOO]? calcd. 476.2, found 476.2. 2.2.10. tert-Butyl (R)-(3-methyl-1-oxo-1-((4-sulphamoylphenethyl)amino)butan-2-yl)carbamate (10) White solid (90%); mp 160C161?C; 1H-NMR (400?MHz, DMSO-d6): 8.02 (t, 1H, Nfor C18H29N3O5S [M?+?Na]+ calcd. 422.2, found 422.3; [M?+?HCOO]? calcd. 444.2, found 444.2. 2.2.11. tert-Butyl ((2R,3R)-3-methyl-1-oxo-1-((4-sulphamoylphenethyl)amino)pentan-2-yl)carbamate (11) White solid (91%); mp 191C192?C; KJ Pyr 9 1H-NMR (400?MHz, DMSO-d6): 7.98 (t, 1H, N+ CHCH(CH3)Cfor C19H31N3O5S [M?+?Na]+ calcd. 436.2, found 436.3; [M-H]? calcd. 412.2, found 412.2; [M?+?HCOO]?calcd. 458.2, found 458.2. 2.2.12. Benzyl (R)-(1,4-dioxo-1,4-bis((4-sulphamoylphenethyl)amino)butan-2-yl)carbamate (12) White solid (73%); mp 249C250?C; 1H-NMR (400?MHz, DMSO-d6): 8.02 (t, 1H, N+ N+ NHCH2Cfor C28H33N5O8S2 [M?+?H]+ calcd. 632.2, found 632.4; [M-H]? calcd. 630.2, found 630.3. 2.3. General process of the formation of amino acidCsulphonamide conjugates, 13C24 N-protected aminoacylbenzotriazole (1.0 equiv.), (4-sulphamoylphenyl)methanaminium chloride (1.0 equiv.), and Et3N (2.5 equiv.) had been put through microwave irradiation (100?W, 70?C) in DCM (5?ml) for 30?min. After conclusion of the response (monitoring TLC dish), all volatiles had been eliminated by rotavapour as well as the acquired crude item was crystallised from ethanol. 2.3.1. Benzyl (R)-(4-methyl-1-oxo-1-((4-sulphamoylbenzyl)amino)pentan-2-yl)carbamate (13) White solid (74%); mp 173C174?C; 1H-NMR (300?MHz, DMSO-d6): 8.60 (t, 1H, CON+ Nfor C21H27N3O5S [M?+?H]+ calcd. 434.2, found 434.3[M?+?Na]+ calcd. 466.2, found 466.3; [M?+?HCOO]? calcd. 478.2, found 478.2. 2.3.2. Benzyl (R)-(4-(methylthio)-1-oxo-1-((4-sulphamoylbenzyl)amino)butan-2-yl)carbamate (14) White solid (80%); mp 167C168?C; 1H-NMR (300?MHz, DMSO-d6): 8.59 (t, 1H, CON+ Nfor C20H25N3O5S2 [M?+?H]+ calcd. 452.1, found 452.2; [M?+?HCOO]? calcd. 496.2, found 496.2. 2.3.3. Benzyl (R)-(3-methyl-1-oxo-1-((4-sulphamoylbenzyl)amino)butan-2-yl)carbamate (15) White solid (89%); mp 141C142?C; 1H-NMR (300?MHz, DMSO-d6): 8.58 (t, 1H, CON+ OCONfor C20H25N3O5S [M?+?H]+ calcd. 420.2, found 420.2; [M?+?Na]+ calcd. 442.1, found 442.3; [M?+?HCOO]?calcd. 464.2, found 464.2. 2.3.4. Benzyl (S)-(1-oxo-3-(phenylthio)-1-((4-sulphamoylbenzyl)amino)propan-2-yl)carbamate (16) White solid (72%); mp 196C197?C; 1H-NMR (300?MHz, DMSO-d6): 8.76 (t, 2H, CON+ OCONfor C24H25N3O5S2 [M?+?H]+ calcd. 500.1, found 500.3; [M?+?HCOO]? calcd. 544.1, found 544.2. 2.3.5. tert-Butyl (2-oxo-2-((4-sulphamoylbenzyl)amino)ethyl)carbamate (17) White colored solid (70%); mp 172C173?C; 1H-NMR (300?MHz, DMSO-d6): 8.41 (t, 1H, CONfor C14H21N3O5S [M?+?Na]+ calcd. 366.1, found 366.1; [M-H]? calcd. 342.1, found 342.1; [M?+?HCOO]? calcd. 388.1, found 388.1. 2.3.6. tert-Butyl (R)-(1-oxo-1-((4-sulphamoylbenzyl)amino)propan-2-yl)carbamate (18) White solid (85%); mp 197C198?C; 1H-NMR.