Modification of an Anti-tubercular Molecule

First efficient synthesis of (±)-erythro-roccellic acid†

“…A solution of the mixture of 3 and 4 (3.3 g) in THF (15 mL) and triethylamine (15 mL) was refluxed for 48 h with stirring. The reaction mixture was then allowed to reach rt, and was concentrated in vacuo; silica gel column chromatographic purification of the residue using petroleum spirit-ethyl acetate (9 : 1) gave pure 5 (3.23 (6), 228 (10), 215 (100), 203 (8), 107 (48), 91 (29), 81 (41), 67 (20), 55 (10) (Calc. for C 24 H 35 NO 2 : C, 78.00; H, 9.55; N, 3.80.…”

“…The reaction mixture was concentrated in vacuo and the residue was acidified with dilute HCl, extracted with diethyl ether (3 × 50 mL) and the organic layer was washed with water (20 mL), brine (20 mL) and dried over Na 2 SO 4 . Concentration of the organic layer in vacuo followed by silica gel column chromatographic purification of the residue using petroleum spirit-ethyl acetate (9 : 1) furnished pure 6 as a thick oil (0.82 g, 98%); IR (Nujol) ν max 1823, 1767, 1674, 1466 cm Ϫ1 ; 1 H NMR δ H 0.88 (t, J 6 Hz, 3 H), 1.26 (br s, 18 H), 1.45-1.70 (m, 2 H), 2.07 (s, 3 H), 2.46 (t, J 6 Hz, 2 H); 13 C NMR (CDCl 3 , 50 MHz) δ C 9.2, 13.9, 22.5, 24.3, 27.4, 29.3, 29.5 (6 × CH 2 ), 31.8, 140.3, 144.6, 165.7, 166.1; MS m/z 281 (MH ϩ , 10%), 262 (18), 252 (12), 235 (13), 207 (20), 196 (14), 178 (42), 168 (29), 150 (15), 139 (10), 126 (95), 109 (12), 98 (26), 81 (33), 67 (30)…”

“…The reaction mixture was filtered through Celite and the filtrate was concentrated in vacuo. The silica gel column purification of the residue using petroleum spirit-ethyl acetate (9 : 1) (29), 203 (80), 175 (7), 134 (12), 107 (20), 91 (12), 69 (18) (Calc. for C 24 H 37 NO 2 : C, 77.58; H, 10.03; N, 3.77.…”

“…The excess of diazomethane was quenched with acetic acid and the reaction mixture was concentrated in vacuo. Silica gel column chromatographic purification of the residue using petroleum spirit and ethyl acetate mixture (9 : 1) gave pure 10 as a thick oil (0.32 g, 98%); IR (neat) ν max 1740, 1464, 1435, 1195 cm Ϫ1 ; 1 H NMR (CDCl 3 , 200 MHz) δ H 0.87 (t, J 6 Hz, 3 H), 1.13 (d, J 6 Hz, 3 H), 1.23 (br s, 18 H), 1.30-1.50 (m, 2 H), 1.50-1.75 (m, 2 H), 2.58-2.78 (m, 2 H), 3.68 (s, 3 H), 3.69 (s, 3 H); 13 C NMR (CDCl 3 , 75 MHz) δ C 14.0, 15.1, 22.7, 27.5, 29.4, 29.6 (6 × CH 2 ), 30.7, 31.9, 42.1, 48.6, 51.4, 51.7, 174.6, 175.3; MS m/z 328 (M ϩ , 1%), 298 (24), 267 (7), 242 (100), 184 (16), 170 (18), 160 (88), 128 (66), 111 (17), 101 (32), 91 (68), 81 (29)…”

A new route to (±)-erythro-roccellic acid and chaetomellic anhydride C through functional rearrangement, promoted by n-propylamine or CH3ONa/CH3OH, of N-propyl-3-chloro-4-dichloromethyl-3-dodecylpyrrolidin-2-one

“…This dibasic fatty acid has been used in the preparation of actinonin antibiotic analogues, 10 in the precipitation of human serum albumin 11 and in the assembly of metal complexes. 12 In addition, it displays (as the sodium salt of the ethyl half-ester) antituberculosis activity 13,14 and acts as a plant concentration-dependent growth promoter 15 or inhibitor. 16 Barry and Twomey were the first to obtain (G)-1, albeit as a minor compound of a mixture of erythro/threo diastereoisomers, by successive alkylations of diethyl malonate.…”