Trifluoroacetic acid → (13E)-10-[(3-chloro-4-methoxyphenyl)methyl]-6-methyl-3-(2-methylpropyl)-16-[1-(3-phenyloxiran-2-yl)ethyl]-1,4-dioxa-8,11-diazacyclohexadec-13-ene-2,5,9,12-tetrone

Participants

Reaction Steps

To a solution of Cryptophycin 53 (5 mg, 0.007 mmol) in 0.5 mL of dry benzene was added triphenylphosphine sulfide (4 mg, 0.014 mmol) followed by 0.65 μL of trifluoroacetic acid as a solution in dry benzene (100 μl). The solution was allowed to stir at room temperature for 6 h, neutralized with sodium bicarbonate, filtered and evaporated. The residue was partitioned between water and CH2Cl2. The CH2Cl2 -soluble material was purified by reversed-phase HPLC on C18 using 4:1 MeCN/H2O to obtain pure Cryptophycin 61 (1.9 mg, 37%). 1H NMR (300 MHz, CDCl3) unit A 7.24-7.35 (10/11/12/13/14-H; m), 6.73 (3-H; ddd, 15.0/10.2/4.8), 5.67 (2-H; d, 15.0), 5.23 (5-H; bm, W1/2 ≈15 Hz), 3.68 (8-H; d, 5.1), 3.01 (7-H; dd, 8.3/5.1), 2.52 (4-Hb ; bm, W1/2 ≈15 Hz), 2.41 (4-Ha ; ddd, -14.6/11.1/10.8), 1.6-1.8 (6-H; m), 1.15 (6-Me; d, 6.9); unit B 7.18 (5-H; d, 2.1), 7.04 (9-H; dd, 8.4/2.1), 6.84 (8-H; d, 8.4), 5.45 (NH; d, 7.8), 4.75 (2-H; ddd, 7.8/7.2/6.9), 3.88 (OMe; s), 3.08 (3-Hb /3-Ha ; bm, W1/2 ≈15 Hz); unit C 7.17 (NH; m), 3.40 (3-Hb ; dd, -13.6/8.4), 3.13 (3-Ha ; dd, -13.6/3.6), 1.23* (2-Me; s), 1.16* (2-Me'; s); unit D 4.86 (2-H; dd, 9.9/3.6), 1.6-1.8 (3-Hb /4-H, m), 1.43 (3-Ha ; bm, W1/2 ≈15 Hz), 0.92.dagger. (4-Me; d, 6.6), 0.88.dagger. (5-H3 ; d, 6.6).

Provenance & Evidence