344 Journal of Medicinal Chemistry, 2009, Vol. 52, No. 2
Venkatraman et al.
(dd, 1 H, J ) 5.4 and 4.7 Hz), 3.64 (dt, 1 H, J ) 4.4 and 9.7 Hz),
3.07-2.87 (m, 4 H), 2.67 (s, 3 H), 1.70-1.62 (m, 2 H), 1.45-0.87
(m, 18 H), 0.99 (s, 3 H), 0.85 (s, 3 H), 0.81 (s, 9 H), 0.42-0.39
(m, 2 H), 0.21-0.18 (m, 2 H). 13C NMR (125 MHz, CDCl3), δ,
198.5, 172.0, 171.7, 162.0, 158.2, 133.8, 133.0, 128.9, 137.7, 60.4,
55.7, 52.7, 51.4, 47.6, 43.7, 36.0, 35.0, 32.2, 31.6, 31.3, 28.4, 27.8,
28.0, 27.4, 27.1, 27.0, 26.9, 26.6, 26.3, 24.4, 22.3, 19.4, 13.6, 11.4,
4.1, 4.0. MS (ESI, m/z relative intensity), 799 [(M + Na)+, 60],
777 [(M + 1)+, 100].
(16aS,17aR,17bS)-13(S)-[[[[2,2-Dimethyl-1(S)-[[methyl(2-thienylsul-
fonyl)amino]methyl]propyl]amino]carbonyl]amino]octadecahydro-
17,17-dimethyl-r,1,14-trioxo-N-(2-propenyl)-2H-cyclopropa[3,4]pyrrolo-
[1,2-a][1,4]diazacyclohexadecine-3(S)-acetamide [44]. 1H NMR (500
MHz, DMSO-d6), δ, 8.06 (bs, 1 H), 7.62 (dd, 1 H, J ) 1.3 and 3.8
Hz), 7.57 (dd, 1 H, J ) 1.3 and 2.5 Hz), 7.49 (b, 1H), 7.16 (dd, 1
H, J ) 3.8 and 1.3 Hz), 5.93-5.67 (m, 2 H), 5.69 (bt, 1 H, J ) 8.2
Hz), 5.27-5.19 (m, 2 H), 4.72 (m, 1 H), 4.63 (s, 1 H), 4.31 (d, 1
H, J ) 10.4 Hz), 4.06-3.90 (m, 5 H), 2.93-2.77 (m, 2 H), 2.85
(s, 3 H), 1.92-1.31 (m, 20 H), 1.04 (s, 3 H), 0.93 (s, 3 H), 0.91 (s,
9 H). 13C NMR (125 MHz, CDCl3), δ, 198.5, 173.7, 171.7, 159.3,
158.2, 138.7, 133.3, 132.2, 131.9, 127.9, 117.6, 60.7, 54.9, 53.7,
51.7, 51.0, 48.4, 42.2, 35.2, 34.5, 33.4, 32.5, 31.0, 27.9, 27.3, 27.1,
27.3, 26.9, 26.4, 25.8, 25.0, 23.3, 26.7, 19.3, 13.5. MS (ESI, m/z
relative intensity) 817 [(M + Na + CH3OH)+, 60], 795 [(M +
Na)+, 65], 763 [(M + 1)+, 100]. HRMS calcd for C37H58NaN6O7S2
[M + Na]+: 785.3706. Found: 785.3706.
(16aS,17aR,17bS)-13(S)-[[[[1(S)-(Cyclopropylcarbonyl)-2-methyl-
propyl]amino]carbonyl]amino]octadecahydro-17,17-dimethyl-r,1,14-
trioxo-N-(2-propenyl)-2H-cyclopropa[3,4]pyrrolo[1,2-a][1,4]diazacyclo-
hexadecine-3(S)-acetamide [45]. 1H NMR (500 MHz, DMSO-d6), δ,
8.89 (t, 1 H, J ) 5.7 Hz), 8.37 (d, 1 H, J ) 9.1 Hz), 6.39 (d, 1 H,
J ) 8.8 Hz), 6.23 (d, 1 H, J ) 8.8 Hz), 5.85-5.36 (m, 1H), 5.30
(t, 1 H, J ) 9.7 Hz), 5.14-5.06 (m, 2 H), 4.35 (s, 1 H), 4.26 (dt,
1 H, J ) 1.9 and 10.1 Hz), 3.91-3.71 (m, 4 H), 2.21-2.15 (m, 2
H), 1.73-1.64 (m, 2 H), 1.52-0.72 (m, 23 H), 1.00 (s, 3 H), 0.87
(s, 3 H), 0.70 (d, 6 H, J ) 6.6 Hz). 13C NMR (125 MHz, CDCl3),
δ, 210.8, 198.2, 172.0, 171.4, 162.1, 157.9, 135.0, 116.4, 64.5, 60.5,
52.8, 51.4, 47.6, 41.7, 32.1, 31.5, 31.2, 30.1, 28.3, 28.0, 27.8, 27.3,
26.9, 26.6, 26.2, 24.4, 22.4, 20.4, 19.4, 18.8, 17.8, 13.6, 11.7, 11.2,
8.5. MS (ESI, m/z relative intensity), 628 [(M + 1)+, 100], 461
(20), 450 (10).
(16aS,17aR,17bS)-13(S)-[[[[2,2-Dimethyl-1(S)-[[methyl(2-pyridinyl-
sulfonyl)amino]methyl]propyl]amino]carbonyl]amino]octadecahydro-
17,17-dimethyl-r,1,14-trioxo-N-(2-propenyl)-2H-cyclopropa[3,4]-
pyrrolo[1,2-a][1,4]diazacyclohexadecine-3(S)-acetamide [48]. 1H NMR
(500 MHz, DMSO-d6), δ, 8.89 (t, 1 H, J ) 5.9 Hz), 8.72 (d, 1H,
J ) 5.1 Hz), 8.37 (d, 1 H, J ) 8.8 Hz), 8.07 (t, 1 H, J ) 7.3 Hz),
7.88 (d, 1 H, J ) 7.3 Hz), 7.66 (dd, 1 H, J ) 5.1 and 2.9 Hz), 6.13
(d, 1 H, J ) 8.8 Hz), 5.84-5.73 (m, 2 H), 5.28 (t, 1 H, J ) 9.5
Hz), 5.06 (dd, 2 H, J ) 18.0 and 3.0 Hz), 4.30 (s, 1 H), 4.25 (t, 1
H, J ) 8.8 Hz), 3.92 (d, 1 H, J ) 10.3 Hz), 3.77-3.60 (m, 4 H),
3.20 (d, 1 H, J ) 10.2 Hz), 3.05 (t, 1 H, J ) 10.2 Hz), 2.75 (s, 3
H), 1.63 (m, 1 H), 1.45-0.83 (m, 19 H), 0.97 (s, 3 H), 0.83 (s, 3
H), 0.77 (s, 9 H). 13C NMR (125 MHz, DMSO-d6), δ, 198.3, 172.1,
171.7, 162.1, 162.0, 158.3, 157.1, 151.1, 139.6, 135.0, 128.0, 123.3,
116.5, 60.5, 55.8, 52.8, 52.3, 51.5, 47.6, 41.7, 36.4, 35.0, 32.2, 31.8,
31.6, 28.5, 28.0, 27.9, 27.4, 27.2, 27.1, 26.9, 26.6, 26.3, 22.3, 19.5,
15.0, 13.7. MS (ESI, m/z relative intensity) 780 [(M + Na)+, 50],
758 [(M + H)+, 100].
198.2, 172.0, 171.6, 162.0, 158.1, 135.0, 116.4, 60.4, 55.8, 52.8,
51.6, 51.3, 47.6, 41.7, 38.5, 36.0, 34.9, 32.3, 31.6, 31.2, 28.4, 27.9,
27.3, 27.1, 27.0, 26.9, 26.6, 26.2, 24.4, 22.3, 19.4, 13.6. MS (ESI,
m/z relative intensity) 724 [(M + 1)+, 100], 461 (10).
(16aS,17aR,17bS)-13(S)-[[[[1(S)-[(1,3-Dihydro-1,3-dioxo-2H-isoin-
dol-2-yl)methyl]-2,2-dimethylpropyl]amino]carbonyl]amino]octa-
decahydro-17,17-dimethyl-r,1,14-trioxo-N-(2-propenyl)-2H-
cyclopropa[3,4]pyrrolo[1,2-a][1,4]diazacyclohexadecine-3(S)-
acetamide [51]. 1H NMR (500 MHz, DMSO-d6), δ, 8.87 (t, 1 H, J
) 6.0 Hz), 8.32 (d, 1 H, J ) 9.1 Hz), 7.83 (bs, 4 H), 5.99 (d, 1 H,
J ) 8.8 Hz), 5.84 (d, 1 H, J ) 10.4 Hz), 5.82-5.75 (m, 1 H), 5.24
(bt, 1 H, J ) 10.4 Hz), 5.13-5.05 (m, 2 H), 4.27 (s, 1 H), 3.88 (dt,
1 H, J ) 4.1 and 9.4 Hz), 3.79-3.49 (m, 7 H), 1.66-1.63 (m, 1
H), 1.39-0.92 (m, 19 H), 0.96 (s, 3 H), 0.93 (s, 9 H), 0.77 (s, 3
H). 13C NMR (125 MHz, CDCl3), δ, 198.1, 171.9, 171.0, 168.6,
162.1, 158.0, 135.0, 135.0, 132.5, 123.6, 116.4, 60.4, 56.2, 52.9,
51.3, 47.4, 41.6, 39.5, 34.3, 31.9, 31.4, 31.2, 28.2, 27.8, 27.8, 27.1,
27.0, 26.8, 26.5, 26.0, 24.5, 22.2, 19.3, 13.5. MS (ESI, m/z relative
intensity) 755 [(M + Na)+, 40], 733 [(M + 1)+, 100].
(16aS,17aR,17bS)-13(S)-[[[[1(S)-[(4,4-Dimethyl-2,6-dioxo-1-pi-
peridinyl)methyl]-2,2-dimethylpropyl]amino]carbonyl]amino]-
octadecahydro-17,17-dimethyl-r,1,14-trioxo-N-(2-propenyl)-2H-
cyclopropa[3,4]pyrrolo[1,2-a][1,4]diazacyclohexadecine-3(S)-ac-
1
etamide [52]. H NMR (500 MHz, DMSO-d6), δ, 8.10 (t, 1 H, J
) 5.7 Hz), 8.37 (d, 1 H, J ) 8.8 Hz), 6.19 (d, 1H, J ) 8.5 Hz),
5.83-5.75 (m, 1 H), 5.58 (d, 1 H, J ) 10.4 Hz), 5.27 (bt, 1 H, J
) 9.1 Hz), 5.13-5.05 (m, 2 H), 4.31 (s, 1 H), 4.18 (t, 1 H, J ) 8.8
Hz), 3.83- 3.65 (m, 6 H), 3.58 (d, 1 H, J ) 12.6 Hz), 2.43 (dd, 4
H, J ) 17.0 and 11.0 Hz), 1.66-1.62 (m, 2 H), 1.44-1.11 (m, 18
H), 0.98 (s, 3 H), 0.96 (s, 6 H), 0.84 (s, 9 H), 0.82 (s, 3 H). 13C
NMR (125 MHz, DMSO-d6), δ, 198.2, 172.8, 172.0, 171.3, 162.1,
158.1, 135.0, 116.4, 60.4, 55.4, 52.8, 51.3, 47.5, 46.3, 41.7, 39.5,
35.0, 32.4, 31.5, 31.2, 29.2, 28.3, 27.9, 27.9, 27.3, 27.0, 26.9, 26.5,
26.1, 24.5, 22.4, 19.4, 13.6. MS (ES, m/z relative intensity) 749
[(M + Na)+, 20], 727 [(M + 1)+, 100].
(16aS,17aR,17bS)-13(S)-[[[[2,2-Dimethyl-1(S)-[(4-methyl-2,
6-dioxo-1-piperazinyl)methyl]propyl]amino]carbonyl]amino]-
octadecahydro-17,17-dimethyl-r,1,14-trioxo-N-(2-propenyl)-2H-
cyclopropa[3,4]pyrrolo[1,2-a][1,4]diazacyclohexadecine-3(S)-
acetamide [53]. 1H NMR (500 MHz, CDCl3): δ, 8.00 (1H, d, J )
7.88 Hz), 7.61 (1H, broad s), 5.95 (1H, broad s), 5.85 (1H, ddt, J
) 5.67, 10.40, 17.02 Hz), 5.63 (1H, t, J ) 8.51 Hz), 5.21 (1H, ddt,
J ) 1.26, 1.57, 17.02 Hz), 5.19 (1H, broad s), 5.18 (1H, dd, J )
1.26, 10.40 Hz), 4.60 (1H, ddd, J ) 3.46, 9.45, 10.40 Hz), 4.54
(1H, s), 4.11 (1H, d, J ) 10.08 Hz), 3.79-4.02 (6H, m), 3.42 (2H,
d, J ) 16.07 Hz), 3.33 (2H, d, J ) 16.07 Hz), 2.37 (3H, s), 1.84
(4H, m), 1.68 (1H, m), 1.43-1.52 (4H, m), 1.15-1.42 (10H, m),
1.05 (1H, m), 0.96 (3H, s), 0.91 (9H, s), 0.81 (3H, s). 13C NMR
(125 MHz, CDCl3), δ, 198.2, 172.9, 171.3, 170.1, 158.8, 157.5,
132.9, 117.2, 60.2, 58.0, 55.9, 53.1, 51.1, 48.1, 43.7, 41.8, 39.4,
34.2, 33.5, 32.3, 30.8, 29.2, 27.3, 26.9, 26.87, 26.84, 26.4, 26.3,
26.0, 25.4, 24.5, 22.8, 18.9, 13.0 ppm. HRMS (ESI) calcd for
C37H60N7O7 [M + H]+: 714.4554. Found: 714.4556.
(16aS,17aR,17bS)-13(S)-[[[[1(S)-[(2,4-Dioxo-3-azabicyclo[3.2.1]oct-
3-yl)methyl]-2,2-dimethylpropyl]amino]carbonyl]amino]octadecahydro-
17,17-dimethyl-r,1,14-trioxo-N-(2-propenyl)-2H-cyclopropa[3,4]pyr-
1
rolo[1,2-a][1,4]diazacyclohexadecine-3(S)-acetamide [54]. H NMR
(500 MHz, CDCl3): δ, 8.03 (1H, d, J ) 6.6 Hz), 7.69 (1H, broad
s), 6.04 (1H, broad s), 5.85 (1H, ddt, J ) 5.67, 10.08, 17.0 Hz),
5.64 (1H, broad s), 5.22 (1H, ddt, J ) 1.2, 1.5, 17.0 Hz), 5.21 (1H,
broad s), 5.17 (1H, ddt, J ) 1.2, 1.2, 10.0 Hz), 4.64 (1H, d, J )
8.8 Hz), 4.56 (1H, broad s), 4.16 (1H, d, J ) 10.0 Hz), 3.89-4.02
(3H, m), 3.84 (1H, dt, J ) 4.72, 10.0 Hz), 3.73 (1H, s), 3.71 (1H,
d, J ) 6.3 Hz), 3.13 (1H, broad s), 3.08 (1H, broad s), 2.16 (1H,
d, J ) 11. Hz), 2.02 (3H, m), 1.86 (2H, m), 1.70 (5H, m), 1.58
(1H, dt, J ) 4.0, 12.0 Hz), 1.48 (4H, m), 1.14-1.43 (9H, m), 1.05
(1H, m), 0.96 (3H, s), 0.89 (9H, s), 0.81 (3H, s). 13C NMR (125
MHz, CDCl3): δ 198.4, 173.0, 171.3, 158.8, 157.6, 132.9, 117.2,
60.1, 56.0, 53.1, 51.0, 48.1, 44.9, 44.7, 41.8, 38.8, 34.2, 33.6, 32.5,
32.3, 31.5, 30.8, 29.2, 27.3, 27.2, 26.9, 26.87, 26.83, 26.46, 26.42,
(16aS,17aR,17bS)-13(S)-[[[[1(S)-[[[(Dimethylamino)sulfonyl]methy-
lamino]methyl]-2,2-dimethylpropyl]amino]carbonyl]amino]octadec-
ahydro-17,17-dimethyl-r,1,14-trioxo-N-(2-propenyl)-2H-cyclopro-
pa[3,4]pyrrolo[1,2-a][1,4]diazacyclohexadecine-3(S)-acetamide [50]. 1H
NMR (500 MHz, DMSO-d6), δ, 8.89 (t, 1 H, J ) 6.0 Hz), 8.37 (d,
1 H, J ) 9.1 Hz), 6.15 (d, 1 H, J ) 9.1 Hz), 5.83-5.76 (m, 2 H),
5.29 (t, 1 H, J ) 10.1 Hz), 5.14-5.06 (m, 2 H), 4.33 (s, 1 H), 4.30
(t, 1 H, J ) 9.1 Hz), 3.92 (d, 1 H, J ) 10.4 Hz), 3.81-3.71 (m, 3
H), 3.61 (dt, 1 H, J ) 2.5 and 10.4 Hz), 3.17 (dd, 1 H, J ) 2.8 and
10.7 Hz), 2.94 (dd, 1 H, J ) 11.0 and 2.5 Hz), 2.71 (s, 3 H), 2.69
(s, 6 H), 1.71-1.63 (m, 2 H), 1.46-1.17 (m, 18 H), 0.99 (s, 3 H),
0.84 (s, 3 H), 0.81 (s, 9 H). 13C NMR (125 MHz, DMSO-d6), δ,