br Chemistry The test compounds listed in
Chemistry The test compounds listed in Table 1, Table 2, Table 3, Table 4, Table 5, were synthesized as outlined in Scheme 1, Scheme 2, Scheme 3, Scheme 4, Scheme 5. Synthesis of 2–5 is described in Scheme 1. N-Sulfonylation of the aniline 26 with benzenesulfonyl chloride afforded the sulfonamide 29a. N-Sulfonylation of the aniline 27 with benzenesulfonyl chloride and 4-chlorobensenesulfonyl chloride gave sulfonamides 29b and 29c, respectively. Then alkaline hydrolysis of 29a–c led to benzoic acids 30a–c, respectively. N-Sulfonylation of 28 with benzenesulfonyl chloride gave the sulfonamide 29d, reduction of which afforded the aniline 30d. Amidation of 30a–c with methyl 4-aminobenzoate provided amides 31a–c, alkaline hydrolysis of which resulted in the production of 2–4, respectively. N-Acylation of 30d with methyl 4-(chlorocarbonyl)benzoate gave the amide 31d, alkaline hydrolysis of which resulted in 5. Synthesis of 6–9 is outlined in Scheme 2a. Wittig reaction of aldehyde 32 and a phosphonium salt 34 afforded the olefin 35 as a mixture of E- and Z-isomers. Reduction of the nitro residue of 35, followed by separation using silica gel column chromatography, produced Z-isomer and E-isomer . N-Sulfonylation of and with 4-chlorobenzenesulfonyl chloride, followed by alkaline hydrolysis resulted in 7 and 8, respectively. Catalytic hydrogenation of the olefin of 8 gave the phenyl propanoic Cy3 TSA analog 6. C-Acylation of an anion prepared from the phosphonium salt 34 in the presence of tertiary butoxide with an acid chloride 33 afforded betaine 37, heating of which provided the propiolic acid derivative 38. Reduction of the nitro residue of 38 led to the aniline 39, N-sulfonylation of which with 4-chlorobenzenesulfonyl chloride afforded the sulfonamide 41. Alkaline hydrolysis of 41 resulted in the production of 9. Compound 10 was prepared as described in Scheme 2b. Sodium borohydride reduction of 32 afforded an alcohol 42, methanesulfonylation of which provided 43. O-Alkylation of methyl 4-hydroxybenzoate with the methanesulfonate 43 gave 44, reduction of which led to the aniline 45. N-Sulfonylation of 45 with 4-chlorobenzenesulfonyl chloride, followed by alkaline, hydrolysis resulted in the production of 10. Synthesis of 11–12 and 15–25 is described in Scheme 3. Compounds 11–12 and 15–19 were prepared as outlined in Scheme 3a. O-Alkylation of nitrophenols 47a–f with methyl 4-(bromomethyl)benzoate in the presence of potassium carbonate provided benzyl phenyl ethers 48a–f, reduction of which gave anilines 49a–f, respectively. N-Sulfonylation of 49a–f with benzenesulfonyl chloride, followed by alkaline hydrolysis, resulted in the production of 12 and 15–19, respectively. N-Sulfonylation of 49a with 4-chlorobenzenesulfonyl chloride led to the sulfonamide 51a, after which alkaline hydrolysis produced 11. Synthesis of 20–25 is described in Scheme 3b. N-Alkylation of 51e with appropriate alkyl iodides gave N-alkylated sulfonamides 52g–l, alkaline hydrolysis of which resulted in the production of 20–25, respectively. Compound 13 was synthesized as shown in Scheme 4. N-Sulfonylation of aniline with a sulfonyl chloride 53 afforded the sulfonamide 54. Replacement of the fluoro residue of 54 with an alkoxide prepared from the alcohol 55 in the presence of tertiary butoxide led to the aldehyde 56, after which oxidation produced 13. Synthesis of 14 is outlined in Scheme 5. Lithium aluminum hydride reduction of the ester 57 provided the alcohol 58, which was protected as a TBS ether 59. O-Alkylation of 59 with methyl 4-(bromomethyl)benzoate afforded the ether 60, which was deprotected with TBAF to give the alcohol 61. Bromination of 61 with carbon tetrachloride and triphenylphosphine led to the bromide 62. O-Alkyaltion of phenol with 62 provided 63, after which alkaline hydrolysis resulted in the production of 14.
Results and discussion