N. Sewald et al.
Ar-H), 7.20 (d, J=1.9 Hz, 1H; uB-C2’H), 7.15 (dd, J=7.5, 4.9 Hz, 1H;
NH), 7.04 (dd, J=8.4, 1.9 Hz, 1H; uB-C6’H), 6.81 (d, J=8.4 Hz, 1H; uB-
C5’H), 6.62 (d, J=7.9 Hz, 1H; NH), 6.25 (dm, J=17.0 Hz, 1H; uB-
NHC(O)CH=CHA), 6.09 (dd, J=17.0, 10.3 Hz, 1H; uB-NHC(O)CH=
CH2), 5.60 (dd, J=1.1, 10.4 Hz, 1H; uB-NHC(O)CH=CHB), 5.56 (ddm,
J=14.6, 10.1 Hz, 1H; uA-CbH), 4.95–5.05 (m, 3H; uA-CaHA and uA-
CdH and uD-CaH), 4.91 (dm, J=17.0 Hz, 1H; uA-CaHB), 4.75 (ddd, J=
7.5, 6.7, 6.7 Hz, 1H; uB-CaH), 4.71 (d, J=8.9 Hz, 1H; uA-ChH), 4.44 (s,
2H; uA-C4’CH2), 3.87 (dd, J=9.0, 1.8 Hz, 1H; uA-CzH), 3.85 (s, 3H; uB-
C4’OCH3), 3.55 (dd, J=13.3, 8.1 Hz, 1H; uC-CbHA), 3.38 (s, 3H; uA-
CH2OCH3), 3.22 (dd, J=13.4, 4.4 Hz, 1H; uC-CbHB), 3.08 (dd, J=13.9,
6.2 Hz, 1H; uB-CbHA), 2.97 (dd, J=13.9, 6.5 Hz, 1H; uB-CbHB), 2.33
(dm, J=14.9 Hz, 1H; uA-CgHA), 2.25 (ddd, J=14.6, 7.3, 7.3 Hz, 1H; uA-
CgHB), 1.91 (ddq, J=6.6, 1.7, 6.8 Hz, 1H; uA-CeH), 1.65–1.77 (m, 2H;
uD-CbHA and uD-CgH), 1.57 (m, 1H; uD-CbHB), 1.51 (s, 3H; uA-C-
ACTHGNUNERTU(NGN CH3)2), 1.44 (s, 3H; uA-CAHCUTNTRGEN(GNUN CH3)2), 1.28 (s, 9H; uA-CCAHTNUGTREN(NUGN CH3)3), 1.18 (s,
3H; uC-CaCH3), 1.15 (s, 3H; uC-CaCH3), 1.10 (d, J=6.8 Hz, 3H; uA-
CeCH3), 0.95 (d, J=6.0 Hz, 3H; uD-CdH3), 0.88 ppm (d, J=6.2 Hz, 3H;
uD-CdH3); 13C NMR (126 MHz, CDCl3): d=175.6, 171.4, 171.2, 165.0,
153.8, 140.2, 136.4, 132.4, 131.2, 130.6, 129.8, 128.6, 127.7, 126.6, 122.0,
118.6, 111.9, 108.8, 81.7, 80.0, 76.9, 73.5, 70.8, 63.8, 56.0, 54.4, 47.4, 43.8,
39.3, 37.6, 35.7, 34.8, 27.7, 27.2, 27.1, 24.8, 23.3, 23.2, 22.3, 21.2, 9.7 ppm;
MS (ESI): m/z: calcd for [C46H65ClN2O10+Na]+: 863.4; found: 863.6
[M+Na]+.
Cyclic, acetonide-protected depsipeptide 22a (R=H): The seco-ADCB
fragment (R=H) 21a (494 mg; 0.65 mmol) was dissolved in dry CH2Cl2
(65 mL). The commercially available Grubbs second-generation catalyst
(28 mg; 0.033 mmol; 5 mol%) was added and the reaction mixture was
heated at reflux for 6 h. Then the solvent was removed in vacuum
(408C). The residue was purified by flash chromatography on silica gel.
The product was obtained as an amorphous solid (397 mg, 85%). Rf =
0.25 (hexane/EtOAc 1:2); [a]2D4 (0.96 g/100 mL, CHCl3): +14.6; 1H NMR
(500 MHz, CDCl3): d=7.30–7.43 (m, 5H; uA-Ar-H), 7.20 (m, 1H; NH),
7.19 (d, J=1.8 Hz, 1H; uB-C2’H), 7.05 (dd, J=8.3, 1.8 Hz, 1H; uB-C6’H),
6.83 (d, J=8.4 Hz, 1H; uB-C5’H), 6.63 (ddd, J=15.0, 10.7, 4.3 Hz, 1H;
uA-CbH), 5.67 (d, J=15.2 Hz, 1H; uA-CaH), 5.60 (d, J=7.8 Hz, 1H;
NH), 5.04 (ddd, J=10.7, 7.4, 1.0 Hz, 1H; uA-CdH), 4.79 (dd, J=10.3,
3.5 Hz, 1H; uD-CaH), 4.72 (ddm, J=7.6, 5.7 Hz, 1H; uB-CaH), 4.70 (d,
J=8.9 Hz, 1H; uA-ChH), 3.87 (s, 3H; uB-C4’OCH3), 3.79 (dd, J=8.8,
1.8 Hz, 1H; uA-CzH), 3.38 (dd, J=13.4, 8.4 Hz, 1H; uC-CbHA), 3.13 (dd,
J=13.7, 3.3 Hz, 1H; uC-CbHB), 3.11 (dd, J=14.2, 4.9 Hz, 1H; uB-CbHA),
3.02 (dd, J=14.4, 7.7 Hz, 1H; uB-CbHB), 2.47 (dm, J=14.3 Hz, 1H; uA-
CgHA), 2.22 (ddd, J=14.2, 11.2, 11.2 Hz, 1H; uA-CgHB), 1.84 (ddq, J=
6.8, 1.6, 6.8 Hz, 1H; uA-CeH), 1.75 (ddd, J=13.9, 10.4, 5.0 Hz, 1H; uD-
(CH3)2), 1.17 (s, 3H; uC-CaCH3), 1.14 (s, 3H;
ACHTUNGTRENNUNG(CH3)2), 1.45 (s, 3H; uA-CHCATUNGTRENNUGN
uC-CaCH3), 1.11 (d, J=7.0 Hz, 3H; uA-CeCH3), 0.94 (d, J=6.3 Hz, 3H;
uD-CdH3), 0.87 ppm (d, J=6.3 Hz, 3H; uD-CdH3); 13C NMR (126 MHz,
CDCl3): d=175.6, 171.5, 170.9, 164.9, 153.8, 138.5, 137.0, 132.4, 131.2,
130.6, 129.7, 128.6, 128.1, 126.8, 126.7, 122.1, 118.6, 111.9, 108.9, 81.7,
80.1, 76.9, 74.3, 70.8, 58.1, 56.0, 54.3, 47.4, 43.8, 39.4, 37.6, 35.6, 34.9, 27.2,
27.1, 24.8, 23.3, 23.2, 22.3, 21.2, 9.8 ppm; MS (ESI): m/z: calcd for
[C43H59ClN2O10+H]+: 799.4; found: 799.2 [M+H]+; calcd for
[C43H59ClN2O10+Na]+: 821.4; found: 821.4 [M+Na]+; calcd for
[C43H59ClN2O10+Cl]ꢀ: 833.4; found: 833.5 [M+Cl]ꢀ.
seco-ADCB fragment 21c (R=CH2OiPr): The procedure is analogous to
the one given for 21a; starting from unit A building block 2c. Yield:
109 mg (72%); Rf =0.29 (hexane/EtOAc 1:1); [a]2D4 (1.04 g/100 mL,
1
CHCl3): ꢀ25.8; H NMR (500 MHz, CDCl3): d=7.34 (m, 4H; uA-Ar-H),
7.18 (d, J=1.6 Hz, 1H; uB-C2’H), 7.14 (dd, J=7.4, 4.4 Hz, 1H; NH), 7.03
(dd, J=8.3, 1.6 Hz, 1H; uB-C6’H), 6.80 (d, J=8.4 Hz, 1H; uB-C5’H), 6.47
(d, J=7.8 Hz, 1H; NH), 6.25 (dm, J=17.0 Hz, 1H; uB-NHC(O)CH=
CHA), 6.08 (dd, J=17.0, 10.2 Hz, 1H; uB-NHC(O)CH=CH2), 5.61 (dm,
J=10.3 Hz, 1H; uB-NHC(O)CH=CHB), 5.48–5.67 (m, 1H; uA-CbH),
4.89–5.08 (m, 4H; uA-CdH and uA-CaH2 and uD-CaH), 4.75 (ddd, J=
7.1, 6.9, 6.7 Hz, 1H; uB-CaH), 4.70 (d, J=8.8 Hz, 1H; uA-ChH), 4.49 (s,
2H; uA-C4’CH2), 3.85 (s, 3H; uB-C4’OCH3), 3.84–3.88 (m, 1H; uA-CzH),
CbHA), 1.65 (m, 1H; uD-CgH), 1.50 (s, 3H; uA-C
uA-C
(CH3)2), 1.35 (ddd, J=13.7, 9.0, 3.7 Hz, 1H; uD-CbHB), 1.22 (s, 3H;
ACHTUGNTRENUN(NG CH3)2), 1.46 (s, 3H;
AHCTUNGTRENNUNG
uC-CaCH3), 1.15 (s, 3H; uC-CaCH3), 1.13 (d, J=6.9 Hz, 3H; uA-CeCH3),
0.92 (d, J=6.6 Hz, 3H; uD-CdH3), 0.83 ppm (d, J=6.6 Hz, 3H; uD-
CdH3); 13C NMR (126 MHz, CDCl3): d=177.9, 170.4, 170.2, 165.1, 154.1,
142.4, 137.6, 130.9, 129.6, 128.8, 128.6, 128.3, 126.6, 124.4, 122.5, 112.3,
109.1, 82.4, 80.2, 75.8, 71.2, 56.1, 54.4, 46.5, 42.8, 39.5, 36.8, 35.8, 35.3,
27.2, 27.0, 24.7, 23.0, 22.9, 22.7, 21.4, 9.7 ppm; MS (ESI): m/z: calcd for
[C39H51ClN2O9-C3H6O+H]+: 669.3; found: 669.2 [MꢀC3H6O+H]+; calcd
for [C39H51ClN2O9+H]+: 727.3; found: 727.2 [M+H]+; calcd for
[C39H51ClN2O9+Na]+: 749.3; found: 749.2 [M+Na]+; calcd for
[C39H51ClN2O9+Cl]ꢀ: 761.3; found: 761.4 [M+Cl]ꢀ.
3.67 (uA-CHACHTUNGTRENNUNG
(CH3)2), 3.56 (dd, J=13.3, 8.3 Hz, 1H; uC-CbHA), 3.24 (dd,
J=13.4, 4.4 Hz, 1H; uC-CbHB), 3.08 (dd, J=13.9, 6.2 Hz, 1H; uB-CbHA),
2.98 (dd, J=13.9, 6.2 Hz, 1H; uB-CbHB), 2.34 (ddd, J=14.5, 5.2, 5.2 Hz,
1H; uA-CgHA), 2.25 (ddd, J=14.6, 7.3, 7.3 Hz, 1H; uA-CgHB), 1.90
(dqm, J=8.1, 6.9 Hz, 1H; uA-CeH), 1.63–1.77 (m, 2H; uD-CbHA and
uD-CgH), 1.56 (m, 1H; uD-CbHB), 1.50 (s, 3H; uA-C
3H; uA-C(CH3)2), 1.21 (d, J=6.0 Hz, 6H; uA-CH
ACHTUNGTRENNUNG
Cyclic, acetonide-protected depsipeptide 22b (R=CH2OMe): The proce-
dure is analogous to the one given for 22a; starting from 21b. Yield:
76 mg (71%); Rf =0.22 (hexane/EtOAc 1:2); [a]2D4 (0.91 g/100 mL,
CHCl3): +9.6; 1H NMR (600 MHz, CDCl3): d=7.30–7.37 (m, 4H; uA-
Ar-H), 7.22 (dd, J=8.0, 3.4 Hz, 1H; NH), 7.19 (m, 1H; uB-C2’H), 7.05
(dm, J=8.4 Hz, 1H; uB-C6’H), 6.83 (d, J=8.4 Hz, 1H; uB-C5’H), 6.64
(ddd, J=15.0, 10.7, 4.3 Hz, 1H; uA-CbH), 5.75 (d, J=7.8 Hz, 1H; NH),
5.67 (d, J=15.2 Hz, 1H; uA-CaH), 5.03 (ddm, J=10.2, 7.8 Hz, 1H; uA-
CdH), 4.79 (dd, J=10.2, 3.3 Hz, 1H; uD-CaH), 4.71 (m, 1H; uB-CaH),
4.70 (d, J=8.6 Hz, 1H; uA-ChH), 4.45 (s, 2H; uA-C4’CH2), 3.86 (s, 3H;
uB-C4’OCH3), 3.79 (dm, J=8.7 Hz, 1H; uA-CzH), 3.39 (dm, J=8.8 Hz,
1H; uC-CbHA), 3.37 (s, 3H; uA-CH2OCH3), 3.14 (dd, J=10.9, 2.3 Hz,
1H; uC-CbHB), 3.12 (dd, J=13.3, 4.4 Hz, 1H; uB-CbHA), 3.01 (dd, J=
14.5, 8.0 Hz, 1H; uB-CbHB), 2.48 (dm, J=13.4 Hz, 1H; uA-CgHA), 2.22
(ddd, J=14.0, 11.4, 11.4 Hz, 1H; uA-CgHB), 1.82 (dqm, J=6.7, 6.8 Hz,
1H; uA-CeH), 1.76 (ddd, J=13.9, 10.4, 4.9 Hz, 1H; uD-CbHA), 1.67 (m,
N
ACHTUNGTRENNUNG
uC-CaCH3), 1.14 (s, 3H; uC-CaCH3), 1.11 (d, J=7.0 Hz, 3H; uA-CeCH3),
0.94 (d, J=6.2 Hz, 3H; uD-CdH3), 0.87 ppm (d, J=6.3 Hz, 3H; uD-
CdH3); 13C NMR (126 MHz, CDCl3): d=175.6, 171.5, 170.8, 164.9, 153.9,
139.5, 136.7, 132.4, 131.2, 130.6, 129.6, 128.6, 127.9, 126.8, 126.7, 122.1,
118.6, 111.9, 108.9, 81.7, 80.1, 77.0, 71.0 70.8, 69.6, 56.0, 54.3, 47.4, 43.8,
39.3, 37.6, 35.7, 34.9, 27.3, 27.1, 24.8, 23.3, 23.2, 22.3, 22.11, 22.08, 21.2,
9.8 ppm; MS (ESI): m/z: calcd for [C45H63ClN2O10+Na]+: 849.4; found:
849.5 [M+Na]+; calcd for [C45H63ClN2O10ꢀH]ꢀ: 825.4; found: 825.5
[MꢀH]ꢀ; calcd for [C45H63ClN2O10 +Cl]ꢀ: 861.4; found: 861.6 [M+Cl]ꢀ.
seco-ADCB fragment 21d (R=CH2OtBu): The procedure is analogous
to the one given for 21a; starting from unit A building block 2d. Yield:
176 mg (72%); Rf =0.31 (hexane/EtOAc 1:1); [a]2D4 (1.04 g/100 mL,
CHCl3): ꢀ29.3; 1H NMR (500 MHz, CDCl3): d=7.26–7.41 (m, 4H; uA-
Ar-H), 7.17–7.26 (m, 2H; uB-C2’H and NH), 7.05 (dm, J=7.6 Hz, 1H;
uB-C6’H), 6.85 (d, J=7.8 Hz, 1H; NH), 6.80 (d, J=8.4 Hz, 1H; uB-C5’H),
6.24 (dm, J=17.0 Hz, 1H; uB-NHC(O)CH=CHA), 6.10 (dd, J=16.5,
10.2 Hz, 1H; uB-NHC(O)CH=CH2), 5.52–5.66 (m, 2H; uA-CbH and uB-
NHC(O)CH=CHB), 4.88–5.11 (m, 4H; uA-CdH and uA-CaH2 and uD-
CaH), 4.76 (dm, J=6.6 Hz, 1H; uB-CaH), 4.70 (d, J=8.7 Hz, 1H; uA-
ChH), 4.43 (s, 2H; uA-C4’CH2), 3.80–3.87 (m, 4H; uB-C4’OCH3 and uA-
CzH), 3.55 (dd, J=13.2, 8.1 Hz, 1H; uC-CbHA), 3.28 (dd, J=13.2, 4.2 Hz,
1H; uC-CbHB), 3.08 (dd, J=13.7, 5.8 Hz, 1H; uB-CbHA), 2.96 (dd, J=
13.7, 6.8 Hz, 1H; uB-CbHB), 2.32–2.41 (m, 1H; uA-CgHA), 2.26 (ddd, J=
14.5, 7.1, 7.2 Hz, 1H; uA-CgHB), 1.89 (m, 1H; uA-CeH), 1.65–1.78 (m,
2H; uD-CbHA and uD-CgH), 1.56 (m, 1H; uD-CbHB), 1.49 (s, 3H; uA-C-
1H; uD-CgH), 1.50 (s, 3H; uA-C
ACHTUNTRGENNU(G CH3)2), 1.45 (s, 3H; uA-CACHTUNTGERN(NUGN CH3)2), 1.37
(ddd, J=13.9, 8.9, 3.3 Hz, 1H; uD-CbHB), 1.22 (s, 3H; uC-CaCH3), 1.15
(s, 3H; uC-CaCH3), 1.12 (d, J=6.8 Hz, 3H; uA-CeCH3), 0.92 (d, J=
6.6 Hz, 3H; uD-CdH3), 0.83 ppm (d, J=6.5 Hz, 3H; uD-CdH3); 13C NMR
(126 MHz, CDCl3): d=177.8, 170.5, 170.2, 165.2, 154.0, 142.3, 138.7,
137.0, 130.9, 129.8, 128.3, 128.1, 126.7, 124.4, 122.5, 112.3, 109.1, 82.3,
79.9, 75.9, 74.3, 71.1, 58.2, 56.1, 54.5, 46.5, 42.8, 39.5, 36.7, 35.8, 35.3, 27.2,
27.0, 24.7, 23.0, 22.9, 22.7, 21.4, 9.6 ppm; MS (ESI): m/z: calcd for
[C41H55ClN2O10+H]+: 771.4; found: 771.6 [M+H]+; calcd for
[C41H55ClN2O10+Na]+: 793.3; found: 793.6 [M+Na]+; calcd for
[C41H55ClN2O10+Cl]ꢀ: 805.3; found: 805.5 [M+Cl]ꢀ.
11284
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 11273 – 11287