3.6.1. Brevenal Derivatives
In a typical reaction, brevenal was dissolved in DMF and the hydrazide (2 eq) was added, followed by addition of a catalytic amount of tungstophosphoric acid. The reaction mixture was heated at 60 °C for 4 h. The solvents were evaporated under vacuum and the residue was taken up in methanol. The mixture was filtered through a 0.2 μm nylon filter and subjected to purification by HPLC. Desired products were positively identified by HRMS mass spectrometry and NMR. Spectroscopic data collected for all compounds can be found in the supplementary data document.
Compound 11 was prepared by reaction of brevenal with formylhydrazide to give the product as a white solid in 71% yield. 1H NMR (CD3OD), δ 0.89 (t, J = 6 Hz, 1H), 0.96 (d, J = 6 Hz, 3H), 1.03 (s, 3H), 1.12 (s, 3H), 1.18 (s, 3H), 1.34 (m, 6H), 1.50 (m, 2H), 1.62 (m, 4H), 1.75 (m, 6H), 1.86 (m, 5H), 2.03 (m, 5H), 2.21 (m, 3H), 2.36 (m, 1H), 3.24 (m, 2H), 3.33 (m, 2H), 3.54 (br s, 1H), 3.71 (m, 1H), 3.96 (s, 1H), 4.06 (dd, J = 11 Hz and 5 Hz, 1H), 5.08 (d, J = 10 Hz, 1H), 5.18 (d, J = 17 Hz, 1H), 5.44 (q, 1H), 5.90 (dt, J = 16 Hz and 7 Hz, 1H), 6.03 (t, J = 11 Hz, 1H), 6.20 (d, J = 9 Hz, 1H), 6.69 (m, 1H), 8.10 (d, J = 10 Hz, 1H), 8.56 (s, 1H); HRMS calculated for C40H63N2O8 (M + H)+, 699.4579; found 699.4580.
Compound 12 was prepared by reaction of brevenal with acetylhydrazide to give the product as a white solid in 52% yield. 1H NMR (CD3OD), δ 0.91 (t, J = 6 Hz, 1H), 0.97 (d, J = 7 Hz, 3H), 1.05 (s, 3H), 1.13 (s, 3H), 1.20 (s, 3H), 1.31 (m, 6H), 1.50 (m, 2H), 1.64 (m, 4H), 1.75 (m, 6H), 1.86 (m, 5H), 2.04 (m, 5H), 2.21 (m, 3H), 2.33 (m, 1H), 3.25 (m, 2H), 3.35 (m, 2H), 3.54 (m, 1H), 3.64 (s, 3H), 3.69 (t, 1H), 3.97 (m, 1H), 4.08 (m, 1H), 4.21 (m, 1H), 5.09 (d, J = 10 Hz, 1H), 5.19 (d, J = 17 Hz, 1H), 5.45 (m, 1H), 5.90 (m, 1H), 6.05 (m, 1H), 6.69 (m, 1H), 8.19 (d, J = 10 Hz, 1H); HRMS calculated for C41H65N2O8 (M + H)+, 713.4735; found 713.4729.
Compound 13 was prepared by reaction of brevenal with propanoylhydrazide to give the product as a white solid in 39% yield. 1H NMR (CD3OD), δ 0.95 (d, J = 7 Hz, 3H), 1.03 (s, 3H), 1.12 (s, 3H), 1.16 (m, 5H), 1.27 (m, 5H), 1.36 (m, 2H), 1.50 (m, 2H), 1.64 (m, 4H), 1.76 (m, 6H), 1.86 (d, 5H), 2.03 (m, 5H), 2.14 (m, 1H), 2.25 (m, 4H), 2.35 (m, 1H), 2.63 (m, 1H), 3.23 (m, 2H), 3.32 (m, 2H), 3.53 (m, 1H), 3.70 (m, 1H), 3.95 (m, 1H), 4.06 (m, 1H), 5.07 (d, J = 10 Hz, 1H), 5.17 (dd, J = 16 Hz and 2 Hz, 1H), 5.43 (m, 1H), 5.86 (m, 1H), 6.02 (m, 1H), 6.32 (d, J = 10 Hz, 1H), 6.68 (m, 1H), 8.19 (d, J = 10 Hz, 1H); HRMS calculated for C42H67N2O8 (M + H)+, 727.4892; found 727.4885.
Compound 14 was prepared by reaction of brevenal with isobutyrohydrazide to give the product as a white solid in 64% yield. 1H NMR (CD3OD), δ 0.69 (s, 1H), 0.89 (t, J = 7 Hz, 3H), 0.95 (d, J = 7 Hz, 3H), 1.02 (s, 3H), 1.10 (s, 3H), 1.14 (s, 3H), 1.16 (s, 3H), 1.17 (s, 3H), 1.62 (m, 4H), 1.74 (m, 6H), 1.86 (m, 5H), 2.02 (m, 5H), 2.24 (m, 3H), 2.31 (m, 3H), 3.24 (m, 2H), 3.31 (m, 4H), 3.52 (m, 1H), 3.67 (m, 3H), 3.95 (m, 1H), 4.18 (dd, J = 10 Hz and 5 Hz, 2H), 5.07 (d, J = 10 Hz, 1H), 5.17 (d, J = 16 Hz, 1H), 5.87 (m, 1H), 6.02 (m, 1H), 6.31 (d, J = 10 Hz, 1H), 6.67 (m, 1H), 8.22 (d, J = 9 Hz, 1H); HRMS calculated for C43H69N2O8 (M + H)+, 741.5048; found 741.5055.
Compound 15 was prepared by reaction of brevenal with pivaloylhydrazide to give the product as a white solid in 84% yield. 1H NMR (CD3OD), δ 0.95 (d, J = 7 Hz, 3H), 1.02 (s, 3H), 1.11 (s, 3H), 1.18 (s, 3H), 1.23 (s, 9H), 1.28 (m, 2H), 1.35 (m, 3H), 1.50 (m, 2H), 1.62 (m, 3H), 1.74 (m, 6H), 1.84 (m, 5H), 2.03 (m, 6H), 2.23 (m, 3H), 3.23 (m, 2H), 3.30 (m, 5H), 3.53 (m, 1H), 3.70 (m, 1H), 3.96 (t, J = 4 Hz, 1H), 4.05 (m, 1H), 5.07 (d, J = 10 Hz, 1H), 5.17 (d, J = 16 Hz, 1H), 5.43 (m, 1H), 5.88 (t, J = 7 Hz, 1H), 6.02 (t, J = 11 Hz, 1H), 6.33 (d, J = 10 Hz, 1H), 6.68 (dt, J = 17 Hz and 10 Hz, 1H), 8.39 (d, J = 10 Hz, 1H); HRMS calculated for C44H71N2O8 (M + H)+, 755.5205; found 755.5226.
Compound 16 was prepared by reaction of brevenal with cyclohexanoylhydrazide to give the product as a white solid in 55% yield. 1H NMR (CD3OD), δ 0.93 (d, 3H), 1.01 (s, 3H), 1.10 (s, 3H), 1.16 (s, 3H), 1.32 (m, 9H), 1.48 (m, 4H), 1.61 (m, 4H), 1.70–1.80 (m, 9H), 1.84 (m, 7H), 2.01 (m, 7H), 2.21 (m, 5H), 3.21 (m, 2H), 3.51 (m, 1H), 3.67 (m, 1H), 3.93 (m, 2H), 4.03 (m, 1H), 5.05 (d, J = 11 Hz, 1H), 5.15 (d, J = 17 Hz, 1H), 5.41 (m, 1H), 5.85 (m, 1H), 6.00 (t, J = 12 Hz, 1H), 6.30 (d, J = 10 Hz, 1H), 6.67 (m, 1H), 8.18 (d, J = 10 Hz, 1H); HRMS calculated for C46H73N2O8 (M + H)+, 781.5361; found 781.5360.
Compound 17 was prepared by reaction of brevenal with benzoylhydrazide to give the product as a white solid in 45% yield. 1H NMR (CD3OD), δ 0.95 (d, J = 7 Hz, 3H), 1.02 (s, 3H), 1.11 (s, 3H), 1.18 (s, 3H), 1.30 (m, 3H), 1.36 (m, 3H), 1.50 (m, 2H), 1.61 (m, 3H), 1.76 (m, 6H), 1.87 (m, 5H), 2.04 (m, 6H), 2.25 (m, 4H), 3.23 (m, 2H), 3.33 (m, 3H), 3.54 (m, 1H), 3.70 (m, 1H), 3.96 (s, 1H), 4.06 (m, 1H), 5.07 (d, J = 11 Hz, 1H), 5.17 (dd, J = 17 Hz and 2 Hz, 1H), 5.42 (m, 1H), 5.92 (m, 1H), 6.01 (t, J = 11 Hz, 1H), 6.40 (d, J = 10 Hz, 1H), 6.67 (m, 1H), 7.49 (t, J = 7 Hz, 2H), 7.59 (t, J = 7 Hz, 1H), 7.87 (d, J = 7 Hz, 2H), 8.47 (d, J = 10 Hz, 1H); HRMS calculated for C46H67N2O8 (M + H)+, 775.4892; found 775.4892.
Compound 18 was prepared by reaction of brevenal with picalinoylhydrazide to give the product as a pale yellow solid in 43% yield. 1H NMR (CD3OD), δ 0.96 (d, J = 6 Hz, 3H), 1.02 (s, 3H), 1.11 (s, 3H), 1.18 (s, 3H), 1.29 (m, 6H), 1.37 (m, 3H), 1.62 (m, 3H), 1.76 (m, 5H), 1.87 (m, 5H), 2.05 (m, 6H), 2.13 (m, 2H), 2.24 (m, 3H), 3.24 (m, 2H), 3.32 (m, 2H), 3.54 (m, 1H), 3.71 (m, 1H), 3.96 (m, 1H), 4.06 (m, 1H), 5.07 (d, J = 10 Hz, 1H), 5.17 (d, J = 18 Hz, 1H), 5.42 (m, 1H), 5.94 (m, 1H), 6.02 (m, 1H), 6.42 (d, J = 9 Hz, 1H), 6.68 (m, 1H), 7.57 (m, 1H), 7.97 (m, 1H), 8.15 (m, 1H), 8.60 (d, J = 10 Hz, 1H), 8.65 (d, J = 5 Hz, 1H); HRMS calculated for C45H66N3O8 (M+H)+, 776.4844; found 776.4830.
Compound 19 was prepared by reaction of brevenal with nicotinoylhydrazide to give the product as a pale yellow solid in 32% yield. 1H NMR (CD3OD), δ 0.95 (d, J = 7 Hz, 3H), 1.02 (s, 3H), 1.11 (s, 3H), 1.18 (s, 3H), 1.37 (m, 2H), 1.50 (m, 2H), 1.62 (m, 3H), 1.75 (m, 7H), 1.85 (m, 5H), 2.02 (m, 6H), 2.15 (m, 1H), 2.25 (m, 3H), 2.35 (m, 1H), 3.24 (m, 2H), 3.32 (m, 5H), 3.53 (m, 1H), 3.70 (m, 1H), 3.96 (s, 1H), 4.05 (m, 1H), 5.07 (d, J = 10 Hz, 1H), 5.17 (d, J = 16 Hz, 1H), 5.43 (m, 1H), 5.94 (t, J = 8 Hz, 1H), 6.02 (t, J = 11 Hz, 1H), 6.40 (d, J = 10 Hz, 1H), 6.68 (m, 1H), 7.57 (dd, J = 8 Hz and 5 Hz, 1H), 8.30 (d, J = 8 Hz, 1H), 8.47 (d, J = 10 Hz, 1H), 8.71 (d, J = 5 Hz, 1H), 9.03 (s, 1H); HRMS calculated for C45H66N3O8 (M + H)+, 776.4844; found 776.4849.
Compound 20 was prepared by reaction of brevenal with isonicatinoylhydrazide to give the product as a pale yellow solid in 84% yield. 1H NMR (CD3OD), δ 0.94 (d, J = 7 Hz, 3H), 1.01 (s, 3H), 1.10 (s, 3H), 1.17 (s, 3H), 1.26 (m, 5H), 1.35 (m, 3H), 1.50 (m, 2H), 1.60 (m, 3H), 1.74 (m, 6H), 1.84 (m, 4H), 2.01 (m, 5H), 2.12 (m, 1H), 2.23 (m, 2H), 2.32 (m, 1H), 3.22 (m, 2H), 3.31 (m, 3H), 3.52 (m, 1H), 3.69 (m, 1H), 3.94 (t, J = 4 Hz, 1H), 4.04 (m, 1H), 5.05 (d, J = 10 Hz, 1H), 5.15 (d, J = 17 Hz, 1H), 5.41 (m, 1H), 5.93 (t, J = 7 Hz, 1H), 6.00 (t, J = 11 Hz, 1H), 6.39 (d, J = 9 Hz, 1H), 6.67 (m, 1H), 7.83 (d, J = 5 Hz, 2H), 8.49 (d, J = 7 Hz, 1H), 8.70 (d, J = 5 Hz, 2H); HRMS calculated for C45H66N3O8 (M + H)+, 776.4844; found 776.4839.
Compound 21 was prepared by reaction of brevenal with 2-methoxybenzoylhydrazide to give the product as a pale yellow solid in 78% yield. 1H NMR (CD3OD), δ 0.92 (d, J = 7 Hz, 3H), 0.99 (s, 3H), 1.08 (s, 3H), 1.15 (s, 3H), 1.27 (m, 6H), 1.35 (m, 2H), 1.46 (m, 2H), 1.59 (m, 4H), 1.72 (m, 5H), 1.84 (m, 5H), 1.98 (m, 5H), 2.12 (m, 1H), 2.21 (m, 2H), 2.31 (m, 1H), 3.20 (m, 1H), 3.29 (m, 3H), 3.50 (m, 1H), 3.68 (m, 1H), 3.93 (m, 4H), 4.02 (m, 1H), 5.04 (d, J = 10 Hz, 1H), 5.13 (d, J = 17 Hz, 1H), 5.40 (m, 1H), 5.88 (t, J = 7 Hz, 1H), 5.99 (t, J = 11 Hz, 1H), 6.37 (d, J = 10 Hz, 1H), 6.64 (m, 1H), 7.03 (t, J = 7 Hz, 1H), 7.11 (d, J = 8 Hz, 1H), 7.48 (m, 1H), 7.82 (dd, J = 8 Hz and 2 Hz, 1H), 8.36 (d, J = 10 Hz, 1H); HRMS calculated for C47H69N2O9 (M + H)+, 805.4998; found 805.5025.
Compound 22 was prepared by reaction of brevenal with 3-methoxybenzoylhydrazide to give the product as a pale yellow solid in 58% yield. 1H NMR (CD3OD), δ 0.94 (d, J = 7 Hz, 3H), 1.01 (s, 3H), 1.10 (s, 3H), 1.17 (s, 3H), 1.25 (s, 8H), 1.49 (m, 2H), 1.61 (m, 4H), 1.73 (m, 5H), 1.84 (m, 3H), 2.01 (m, 5H), 2.13 (m, 1H), 2.23 (m, 3H), 2.33 (m, 1H), 3.21 (m, 2H), 3.31 (m, 3H), 3.52 (m, 1H), 3.70 (m, 1H), 3.83 (s, 3H), 3.94 (m, 1H), 4.03 (m, 1H), 4.55 (m, 1H), 5.06 (d, J = 10 Hz, 1H), 5.15 (d, J = 15 Hz, 1H), 5.41 (m, 1H), 5.90 (t, J = 8 Hz, 1H), 6.00 (t, J = 11 Hz, 1H), 6.39 (d, J = 10 Hz, 1H), 6.67 (m, 1H), 7.11 (dd, J = 8 Hz and 2 Hz, 1H), 7.37 (t, J = 8 Hz, 1H), 7.43 (m, 2H), 8.46 (d, J = 9 Hz, 1H); HRMS calculated for C47H69N2O9 (M + H)+, 805.4998; found 805.5007.
Compound 23 was prepared by reaction of brevenal with 4-methoxybenzoylhydrazide to give the product as a pale yellow solid in 88% yield. 1H NMR (CD3OD), δ 0.92 (d, J = 7 Hz, 3H), 0.99 (s, 3H), 1.08 (s, 3H), 1.15 (s, 3H), 1.23 (m, 7H), 1.33 (m, 2H), 1.48 (m, 2H), 1.59 (m, 3H), 1.73 (m, 5H), 1.82 (m, 4H), 2.00 (m, 5H), 2.11 (m, 1H), 2.20 (m, 2H), 2.30 (m, 1H), 3.21 (m, 2H), 3.29 (m, 3H), 3.50 (m, 1H), 3.67 (m, 1H), 3.81 (s, 3H), 3.92 (t, J = 4 Hz, 1H), 4.02 (m, 1H), 5.04 (d, J = 10 Hz, 1H), 5.13 (dd, J = 17 Hz and 2 Hz, 1H), 5.40 (m, 1H), 5.87 (t, J = 7 Hz, 1H), 5.99 (t, J = 11 Hz, 1H), 6.37 (d, J = 10 Hz, 1H), 6.64 (m, 1H), 6.97 (d, J = 9 Hz, 2H), 7.83 (d, J = 9 Hz, 2H), 8.42 (d, J = 10 Hz, 1H); HRMS calculated for C47H69N2O9 (M + H)+, 805.4998; found 805.5009.
Compound 24 was prepared by reaction of brevenal with 3-ethoxybenzoylhydrazide (39a) to give the product as a white solid in 41% yield. 1H NMR (CD3OD), δ 0.86 (t, J = 7 Hz, 2H), 0.94 (d, J = 7 Hz, 3H), 1.01 (s, 3H), 1.09 (s, 3H), 1.16 (s, 3H), 1.27 (m, 9H), 1.38 (t, J = 7 Hz, 3H), 1.49 (m, 1H), 1.59 (m, 3H), 1.74 (m, 4H), 1.83 (m, 4H), 2.00 (m, 6H), 2.13 (m, 2H), 2.24 (m, 2H), 2.34 (m, 1H), 3.22 (m, 2H), 3.31 (m, 2H), 3.52 (m, 1H), 3.69 (m, 1H), 3.94 (m, 1H), 4.05 (m, 2H), 5.05 (d, J = 10 Hz, 1H), 5.15 (dd, J = 17 Hz and 1 Hz, 1H), 5.41 (m, 1H), 5.90 (m, 1H), 6.01 (m, 1H), 6.39 (d, J = 10 Hz, 1H), 6.66 (m, 1H), 7.08 (d, J = 8 Hz, 1H), 7.36 (t, J = 8 Hz, 1H), 7.41 (m, 2H), 8.45 (d, J = 10 Hz, 1H); HRMS calculated for C48H71N2O9 (M + H)+, 819.5154; found 819.5159.
Compound 25 was prepared by reaction of brevenal with 3-propoxybenzoylhydrazide (39b) to give the product as a white solid in 64% yield. 1H NMR (CD3OD), δ 0.86 (t, J = 7 Hz, 2H), 0.94 (d, J = 7 Hz, 3H), 1.02 (m, 5H), 1.09 (s, 3H), 1.17 (s, 3H), 1.27 (m, 9H), 1.48 (m, 1H), 1.59 (m, 3H), 1.75 (m, 6H), 1.84 (m, 4H), 2.01 (m, 5H), 2.13 (m, 2H), 2.22 (m, 2H), 2.33 (m, 1H), 3.22 (m, 2H), 3.31 (m, 2H), 3.52 (m, 1H), 3.70 (m, 1H), 3.96 (m, 3H), 4.03 (m, 1H), 5.05 (d, J = 10 Hz, 1H), 5.15 (d, J = 16 Hz, 1H), 5.30 (t, J = 5 Hz, 1H), 5.40 (m, 1H), 5.90 (m, 1H), 6.00 (t, J = 11 Hz, 1H), 6.39 (d, J = 9 Hz, 1H), 6.67 (m, 1H), 7.09 (d, J = 8 Hz, 1H), 7.36 (t, J = 8 Hz, 1H), 7.41 (m, 2H), 8.46 (d, J = 10 Hz, 1H); HRMS calculated for C49H73N2O9 (M + H)+, 833.5311; found 833.5321.
Compound 26 was prepared by reaction of brevenal with 3-isopropoxybenzoylhydrazide (39c) to give the product as a white solid in 41% yield. 1H NMR (CD3OD), δ 0.86 (t, J = 7 Hz, 2H), 0.94 (m, 3H), 1.01 (s, 3H), 1.10 (s, 3H), 1.16 (s, 3H), 1.25 (m, 7H), 1.30 (m, 8H), 1.49 (m, 1H), 1.59 (m, 3H), 1.72 (m, 4H), 1.83 (m, 4H), 2.00 (m, 5H), 2.13 (m, 2H), 2.22 (m, 2H), 3.22 (m, 2H), 3.30 (m, 2H), 3.52 (m, 1H), 3.68 (m, 1H), 3.94 (m, 1H), 4.04 (m, 1H), 4.64 (m, 1H), 5.05 (d, J = 10 Hz, 1H), 5.15 (d, J = 17 Hz, 1H), 5.31 (t, J = 5 Hz, 1H), 5.42 (m, 1H), 5.90 (t, J = 7 Hz, 1H), 6.00 (t, J = 10 Hz, 1H), 6.38 (d, J = 11 Hz, 1H), 6.66 (m, 1H), 7.08 (dd, J = 7 Hz and 2 Hz, 1H), 7.35 (t, J = 9 Hz, 1H), 7.40 (m, 2H), 8.45 (d, J = 10 Hz, 1H); HRMS calculated for C49H73N2O9 (M + H)+, 833.5311; found 833.5294.
Compound 27 was prepared by reaction of brevenal with 3-(allyloxy)benzoylhydrazide (39d) to give the product as a white solid in 77% yield. 1H NMR (CD3OD), δ 0.94 (d, J = 6 Hz, 3H), 1.01 (s, 3H), 1.09 (s, 3H), 1.16 (s, 3H), 1.27 (m, 3H), 1.34 (m, 2H), 1.49 (m, 2H), 1.60 (m, 4H), 1.73 (m, 6H), 1.83 (m, 4H), 2.00 (m, 6H), 2.12 (m, 2H), 2.23 (m, 3H), 2.33 (m, 1H), 3.22 (m, 2H), 3.30 (m, 2H), 3.52 (m, 1H), 3.69 (m, 1H), 3.94 (m, 1H), 4.04 (m, 1H), 4.58 (d, J = 4 Hz, 2H), 5.05 (d, J = 9 Hz, 1H), 5.15 (d, J = 17 Hz, 1H), 5.23 (d, J = 11 Hz, 1H), 5.41 (m, 2H), 5.90 (t, J = 7 Hz, 1H), 6.04 (m, 2H), 6.38 (d, J = 10 Hz, 1H), 6.67 (m, 1H), 7.12 (d, J = 7 Hz, 1H), 7.37 (t, J = 6 Hz, 1H), 7.42 (br s, 2H), 8.45 (d, J = 10 Hz, 1H); HRMS calculated for C49H71N2O9 (M + H)+, 831.5154; found 831.5169.
Compound 28 was prepared by reaction of brevenal with 3,5-dimethoxybenzoylhydrazide (41) to give the product as a pale yellow solid in 78% yield. 1H NMR (CD3OD), δ 0.92 (d, J = 7 Hz, 3H), 0.99 (s, 3H), 1.08 (s, 3H), 1.15 (s, 3H), 1.25 (m, 4H), 1.32 (m, 2H), 1.48 (m, 2H), 1.58 (m, 4H), 1.71 (m, 6H), 1.82 (m, 4H), 1.99 (m, 6H), 2.13 (m, 2H), 2.22 (m, 2H), 2.32 (m, 1H), 3.20 (m, 2H), 3.29 (m, 2H), 3.50 (m, 1H), 3.65 (m, 1H), 3.79 (s, 6H), 3.92 (br s, 1H), 4.02 (m, 1H), 5.04 (d, J = 10 Hz, 1H), 5.14 (d, 1H), 5.40 (m, 1H), 5.89 (m, 1H), 5.99 (t, J = 11 Hz, 1H), 6.36 (d, J = 10 Hz, 1H), 6.64 (m, 2H), 7.00 (s, 2H), 8.44 (d, J = 9 Hz, 1H); HRMS calculated for C48H71N2O10 (M + H)+, 835.5103; found 835.5109.
Compound 29 was prepared by reaction of brevenal with 3-hydroxybenzoylhydrazide to give the product as a white solid in 36% yield. 1H NMR (CD3OD), δ 0.98 (d, J = 7 Hz, 3H), 1.05 (s, 3H), 1.14 (s, 3H), 1.21 (s, 3H), 1.32 (m, 9H), 1.39 (m, 2H), 1.54 (m, 2H), 1.65 (m, 4H), 1.77 (m, 5H), 1.88 (m, 4H), 2.05 (m, 5H), 2.29 (m, 4H), 3.26 (m, 2H), 3.35 (m, 2H), 3.56 (m, 1H), 3.72 (m, 1H), 3.98 (t, J = 4 Hz, 1H), 4.08 (m, 1H), 5.10 (d, J = 10 Hz, 1H), 5.19 (d, J = 18 Hz, 1H), 5.45 (m, 1H), 5.94 (m, 1H), 6.04 (t, J = 10 Hz, 1H), 6.42 (d, J = 10 Hz, 1H), 6.70 (m, 1H), 7.00 (m, 1H), 7.32 (m, 2H), 8.48 (t, J = 10 Hz, 1H); HRMS calculated for C46H67N2O9 (M + H)+, 791.4841; found 791.4818.
Compound 30 was prepared by reaction of brevenal with 3-methylbenzoylhydrazide to give the product as a white solid in 78% yield. 1H NMR (CD3OD), δ 0.98 (d, J = 7 Hz, 3H), 1.05 (s, 3H), 1.14 (s, 3H), 1.21 (s, 3H), 1.30 (m, 3H), 1.39 (m, 2H), 1.54 (m, 2H), 1.64 (m, 4H), 1.78 (m, 6H), 1.87 (m, 5H), 2.05 (m, 6H), 2.18 (m, 1H), 2.28 (m, 3H), 2.36 (m, 1H), 2.43 (s, 3H), 3.26 (m, 2H), 3.35 (m, 2H), 3.57 (m, 1H), 3.73 (m, 1H), 3.98 (t, J = 4 Hz, 1H), 4.08 (m, 1H), 5.10 (d, J = 10 Hz, 1H), 5.19 (dd, J = 17 Hz and 2 Hz, 1H), 5.47 (m, 1H), 5.94 (t, J = 7 Hz, 1H), 6.05 (t, J = 11 Hz, 1H), 6.43 (d, J = 10 Hz, 1H), 6.71 (m, 1H), 7.40 (m, 2H), 7.69 (d, J = 7 Hz, 1H), 7.73 (s, 1H), 8.50 (d, J = 10 Hz, 1H); HRMS calculated for C47H69N2O8 (M + H)+, 789.5048; found 789.5065.
Compound 31 was prepared by reaction of brevenal with 3-dimethylaminobenzoylhydrazide (44a) to give the product as a white solid in 60% yield. 1H NMR (CD3OD), δ 0.98 (d, J = 7 Hz, 3H), 1.05 (s, 3H), 1.14 (s, 3H), 1.21 (s, 3H), 1.29 (m, 3H), 1.39 (m, 2H), 1.53 (m, 2H), 1.64 (m, 4H), 1.77 (m, 6H), 1.88 (m, 5H), 2.04 (m, 6H), 2.16 (m, 1H), 2.28 (m, 3H), 2.38 (m, 1H), 3.01 (s, 6H), 3.26 (m, 2H), 3.34 (m, 2H), 3.57 (m, 1H), 3.74 (m, 1H), 3.98 (t, J = 4 Hz, 1H), 4.08 (m, 1H), 5.10 (d, J = 10 Hz, 1H), 5.19 (dd, J = 17 Hz and 2 Hz, 1H), 5.46 (m, 1H), 5.94 (t, J = 7 Hz, 1H), 6.05 (t, J = 11 Hz, 1H), 6.43 (dd, J = 10 Hz and 3 Hz, 1H), 6.70 (m, 1H), 6.98 (dd, J = 8 Hz and 2 Hz, 1H), 7.19 (d, J = 8 Hz, 1H), 7.27 (br s, 1H), 7.31 (t, J = 8 Hz, 1H), 8.51 (br s, 1H); HRMS calculated for C48H72N3O8 (M + H)+, 818.5314; found 818.5334.
Compound 32 was prepared by reaction of brevenal with 3-fluorobenzoylhydrazide to give the product as a pale yellow solid in 63% yield. 1H NMR (CD3OD), δ 0.94 (d, J = 7 Hz, 3H), 1.01 (s, 3H), 1.10 (s, 3H), 1.17 (s, 3H), 1.27 (m, 3H), 1.36 (m, 2H), 1.49 (m, 2H), 1.61 (m, 4H), 1.73 (m, 6H), 1.86 (m, 5H), 2.01 (m, 6H), 2.12 (m, 1H), 2.24 (m, 3H), 2.34 (m, 1H), 3.23 (m, 2H), 3.31 (m, 2H), 3.52 (m, 1H), 3.69 (m, 1H), 3.94 (t, J = 4 Hz, 1H), 4.04 (m, 1H), 5.06 (d, J = 10 Hz, 1H), 5.15 (dd, J = 17 Hz and 2 Hz, 1H), 5.41 (m, 1H), 5.91 (t, J = 7 Hz, 1H), 6.01 (t, J = 11 Hz, 1H), 6.39 (d, J = 10 Hz, 1H), 6.66 (dt, J = 17 Hz and 11 Hz, 1H), 7.30 (m, 1H), 7.50 (m, 1H), 7.61 (d, J = 8 Hz, 1H), 7.70 (d, J = 7 Hz, 1H), 8.46 (d, J = 10 Hz, 1H); HRMS calculated for C46H66FN2O8 (M + H)+, 793.4798; found 793.4807.
Compound 33 was prepared by reaction of brevenal with 3-chlorobenzoylhydrazide (44b) to give the product as a white solid in 35% yield. 1H NMR (CD3OD), δ 0.98 (d, J = 7 Hz, 3H), 1.05 (s, 3H), 1.14 (s, 3H), 1.21 (s, 3H), 1.30 (m, 3H), 1.38 (m, 2H), 1.54 (m, 2H), 1.65 (m, 4H), 1.77 (m, 6H), 1.89 (m, 5H), 2.05 (m, 6H), 2.17 (m, 1H), 2.28 (m, 3H), 2.38 (m, 1H), 3.27 (m, 2H), 3.34 (m, 2H), 3.56 (m, 1H), 3.73 (m, 1H), 3.99 (t, J = 4 Hz, 1H), 4.08 (m, 1H), 5.09 (d, J = 10 Hz, 1H), 5.19 (d, J = 17 Hz, 1H), 5.45 (m, 1H), 5.96 (t, J = 7 Hz, 1H), 6.05 (t, J = 11 Hz, 1H), 6.43 (d, J = 9 Hz, 1H), 6.70 (m, 1H), 7.51 (t, J = 8 Hz, 1H), 7.61 (d, J = 7 Hz, 1H), 7.84 (d, J = 8 Hz, 1H), 7.93 (t, J = 2 Hz, 1H), 8.50 (d, J = 10 Hz, 1H); HRMS calculated for C46H66ClN2O8 (M + H)+, 809.4502; found 809.4497.
Compound 34 was prepared by reaction of brevenal with 2-(3-methoxyphenyl)acetohydrazide (44c) to give the product as a white solid in 68% yield. 1H NMR (CD3OD), δ 0.97 (d, J = 7 Hz, 3H), 1.05 (s, 3H), 1.14 (s, 3H), 1.20 (s, 3H), 1.33 (m, 3H), 1.38 (m, 2H), 1.53 (m, 2H), 1.64 (m, 4H), 1.77 (m, 6H), 1.88 (m, 5H), 2.05 (m, 6H), 2.15 (m, 1H), 2.25 (m, 3H), 2.38 (m, 1H), 3.26 (m, 2H), 3.33 (m, 2H), 3.54 (m, 3H), 3.72 (m, 1H), 3.79 (s, 3H), 3.98 (d, J = 8 Hz, 1H), 4.08 (m, 1H), 5.10 (d, J = 10 Hz, 1H), 5.19 (dd, J = 17 Hz and 1 Hz, 1H), 5.45 (m, 1H), 5.91 (m, 1H), 6.05 (t, J = 11 Hz, 1H), 6.34 (d, J = 10 Hz, 1H), 6.70 (m, 1H), 6.81 (m, 1H), 6.90 (m, 2H), 7.21 (m, 1H), 8.27 (d, J = 10 Hz, 1H); HRMS calculated for C48H71N2O9 (M + H)+, 819.5154; found 819.5140.
Compound 35 was prepared by reaction of brevenal with 3-(3-methoxyphenyl)propanehydrazide (44d) to give the product as a white solid in 50% yield. 1H NMR (CD3OD), δ 0.97 (d, J = 7 Hz, 3H), 1.05 (s, 3H), 1.14 (s, 3H), 1.20 (s, 3H), 1.27 (m, 2H), 1.39 (m, 3H), 1.52 (m, 2H), 1.65 (m, 4H), 1.76 (m, 6H), 1.87 (m, 5H), 2.04 (m, 6H), 2.16 (m, 1H), 2.26 (m, 3H), 2.39 (m, 1H), 2.54 (t, J = 8 Hz, 2H), 2.95 (m, 3H), 3.22 (m, 2H), 3.34 (m, 2H), 3.55 (m, 1H), 3.72 (m, 1H), 3.77 (s, 3H), 3.98 (dd, J = 5 Hz and 1 Hz, 1H), 4.08 (m, 1H), 5.10 (d, J = 10 Hz, 1H), 5.19 (dd, J = 17 Hz and 2 Hz, 1H), 5.47 (m, 1H), 5.89 (m, 1H), 6.05 (t, J = 11 Hz, 1H), 6.33 (d, J = 10 Hz, 1H), 6.72 (m, 1H), 6.80 (m, 2H), 7.18 (m, 1H), 8.16 (m, 1H); HRMS calculated for C49H73N2O9 (M + H)+, 833.5311; found 833.5289.