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M. van der Knaap et al. / Bioorg. Med. Chem. 17 (2009) 6318–6328
24.72, 24.56, 23.30, 23.14, 19.75, 19.56; HRMS: calcd for
[C74H103N13O11+H]2+
675.90228, found: 675.90263. RP-HPLC:
10–90%, Rt = 8.70 min.
Compound 1e: compound 9 (50 mg, 36
EtOH (2 mL) and ammonium formate (23 mg, 360
added. The solution was purged with argon and 10% Pd/C
(20 mg) was added. The resulting suspension was stirred for 1 h
and filtered through a double Whatman filter. The solution was
concentrated and coevaporated with ethanol to give compound
10 that was used without further purification. Compound 10
13C NMR (151 MHz, MeOH) d 175.57, 173.69, 173.65, 173.56,
172.87, 172.87, 172.53, 139.48, 136.99, 132.43, 130.85, 130.50,
129.78, 128.59, 121.57, 62.14, 62.09, 60.51, 56.07, 56.01, 52.56,
51.57, 48.12, 48.03, 42.10, 40.69, 37.40, 36.79, 32.07, 31.03,
30.90, 30.78, 30.73, 25.76, 24.73, 24.59, 24.55, 23.31, 23.15,
:
l
mol) was dissolved in
l
mol) was
19.75, 19.56, 10.23; HRMS: calcd for [C63H97N13O11+H]2+
:
606.87880, found: 606.87884. RP-HPLC: 10–90%, Rt = 7.45 min.
Compound 1h: compound 9 (50 mg, 36
lmol) was dissolved in
EtOH (2 mL) and ammonium formate (23 mg, 360
lmol) was
added. The solution was purged with argon and 10% Pd/C
(20 mg) was added. The resulting suspension was stirred for 1 h
and filtered through a double Whatman filter. The solution was
concentrated and coevaporated with ethanol to give compound
10 that was used without further purification. Compound 10
(38
redissolved in DCM (2 mL). Under an argon atmosphere Et3N
(3 equiv, 16 L) was added, followed by triphenylacetyl chlo-
ride16 (3 equiv, 35
L). Stirring was continued for 3 h and the
lmol) was coevaporated twice with dichloroethane and
l
l
reaction mixture was concentrated. The residue was taken up
in DCM (1 mL) and TFA (1 mL) was added. After stirring for 1 h,
concentrating under reduced pressure and HPLC purification,
(38
lmol) was coevaporated twice with dichloroethane and redis-
solved in DCM (2 mL). Under an argon atmosphere, Et3N (3 equiv,
16
12
l
l
L) was added, followed by isobutyryl chloride (3 equiv,
L). After 30 min the reaction was concentrated. The residue
compound 1e was obtained in 38% yield (14 lmol, 18 mg) as a
colorless oil.
was taken up in DCM (1 mL) and TFA (1 mL) was added. After stir-
ring for 1 h, concentrating under reduced pressure and HPLC puri-
fication, compound 1h was obtained in 33% yield (12 lmol, 15 mg)
13C NMR (151 MHz, MeOH) d 174.38, 173.69, 173.55, 172.85,
172.51, 144.61, 138.75, 136.98, 133.41, 131.65, 130.82, 130.50,
129.79, 129.06, 128.13, 123.08, 62.13, 60.50, 56.07, 55.98, 55.92,
52.54, 51.55, 47.99, 47.42, 42.09, 40.66, 32.08, 30.87, 30.70,
27.43, 25.75, 25.05, 24.72, 24.56, 23.31, 23.14, 19.75, 19.56, 9.26;
as a colorless oil.
13C NMR (151 MHz, MeOH) d 178.81, 173.74, 173.67, 173.55,
172.90, 172.50, 139.53, 136.97, 132.46, 130.84, 130.49, 129.79,
128.81, 128.61, 121.71, 115.06, 115.01, 62.16, 62.10, 60.51,
56.07, 55.99, 52.54, 51.55, 49.58, 49.43, 49.29, 49.15, 49.01,
48.87, 48.72, 48.15, 48.04, 42.10, 40.70, 40.60, 37.40, 37.05,
36.78, 32.09, 30.88, 30.81, 30.76, 25.76, 24.73, 24.59, 24.55,
23.31, 23.14, 19.95, 19.91, 19.76, 19.56; HRMS: calcd for
[C64H99N13O11+H]2+: 613.88663, found: 613.88671. RP-HPLC: 10–
90%, Rt = 8.42 min.
HRMS: calcd for [C80H107N13O11+H]2+
713.91824. RP-HPLC: 10–90%, Rt = 9.77 min.
Compound 1f: compound 9 (50 mg, 36
:
713.91793, found:
lmol) was dissolved in
EtOH (2 mL) and ammonium formate (23 mg, 360 lmol) was
added. The solution was purged with argon and 10% Pd/C
(20 mg) was added. The resulting suspension was stirred for 1 h
and filtered through a double Whatman filter. The solution was
concentrated and coevaporated with ethanol to give compound
10 that was used without further purification. Compound 10
Compound 1i: compound 9 (50 mg, 36
lmol) was dissolved in
EtOH (2 mL) and ammonium formate (23 mg, 360
lmol) was
(38
solved in DCM (2 mL). Under an argon atmosphere Et3N (3 equiv,
16 L) was added, followed by acetyl chloride (3 equiv, 8 L). Stir-
ring was continued for 30 min and the reaction mixture concen-
trated under reduced pressure. The residue was taken up in
DCM (1 mL) and TFA (1 mL) was added. After stirring for 1 h, con-
centrating under reduced pressure and HPLC purification, com-
l
mol) was coevaporated twice with dichloroethane and redis-
added. The solution was purged with argon and 10% Pd/C
(20 mg) was added. The resulting suspension was stirred for 1 h
and filtered through a double Whatman filter. The solution was
concentrated and coevaporated with ethanol to give compound
10 that was used without further purification. Compound 10
l
l
(36
solved in DCM (2 mL). Under an argon atmosphere, Et3N (10 equiv,
50 L) was added, followed by pivaloyl chloride (5 equiv, 22 L).
lmol) was coevaporated twice with dichloroethane and redis-
pound 1f was obtained in 25% yield (9
lmol, 11 mg) as an off-
l
l
white oil.
Stirring was continued for 8 h and the reaction was concentrated.
The residue was taken up in DCM (1 mL) and TFA (1 mL) was
added. After stirring for 1 h, concentrating under reduced pressure
and HPLC purification, compound 1i was obtained in 27% yield
13C NMR (151 MHz, MeOH) d 173.72, 173.68, 173.67, 173.67,
173.54, 172.89, 172.89, 172.49, 171.86, 139.41, 136.96, 132.53,
130.85, 130.85, 130.49, 129.79, 129.79, 128.81, 128.61, 121.58,
121.58, 62.14, 62.10, 60.51, 56.06, 56.00, 52.54, 51.55, 49.58,
49.43, 49.29, 49.15, 49.01, 48.87, 48.72, 48.12, 48.04, 42.10,
40.70, 37.39, 36.77, 32.09, 30.88, 30.78, 30.75, 25.76, 24.73,
24.58, 24.55, 23.84, 23.31, 23.14, 19.76, 19.57; HRMS: calcd for
[C62H95N13O11+H]2+: 599.87098, found: 599.87095. RP-HPLC: 10–
90%, Rt = 7.82 min.
(10 lmol, 12 mg) as a colorless oil.
13C NMR (151 MHz, MeOH) d 180.14, 173.73, 173.73, 173.64,
173.61, 173.56, 172.86, 172.86, 172.54, 172.54, 139.29, 136.98,
132.89, 130.69, 130.50, 129.78, 128.59, 123.16, 62.17, 62.08,
60.52, 56.07, 55.98, 52.56, 51.56, 48.15, 48.02, 42.09, 40.69,
40.59, 40.54, 37.39, 36.77, 32.06, 30.89, 30.79, 27.81, 25.75,
24.73, 24.60, 24.54, 23.31, 23.14, 19.75, 19.58; HRMS: calcd for
Compound 1g: compound 9 (50 mg, 36
EtOH (2 mL) and ammonium formate (23 mg, 360
l
mol) was dissolved in
lmol) was
[C65H101N13O11+H]2+
10–90%, Rt = 8.41 min.
Compound 1j: compound 9 (50 mg, 36
EtOH (2 mL) and ammonium formate (23 mg, 360
: 620.89445, found: 620.89479. RP-HPLC:
added. The solution was purged with argon and 10% Pd/C
(20 mg) was added. The resulting suspension was stirred for 1 h
and filtered through a double Whatman filter. The solution was
concentrated and coevaporated with ethanol to give compound
10 that was used without further purification. Compound 10
lmol) was dissolved in
lmol) was
added. The solution was purged with argon and 10% Pd/C
(20 mg) was added. The resulting suspension was stirred for 1 h
and filtered through a double Whatman filter. The solution was
concentrated and coevaporated with ethanol to give compound
10 that was used without further purification. Compound 10
(36
lmol) was coevaporated twice with dichloroethane and redis-
solved in DCM (2 mL). Under an argon atmosphere, Et3N (5 equiv,
25
10
l
l
L) was added, followed by propionyl chloride (3 equiv,
L). Stirring was continued for 2 h and the reaction concen-
(36
solved in DCM (2 mL). Under an argon atmosphere, Et3N (3 equiv,
15 L) was added, followed by acetyl chloride (3 equiv,
lmol) was coevaporated twice with dichloroethane and redis-
trated. The residue was taken up in DCM (1 mL) and TFA (1 mL)
was added. After stirring for 1 h, concentrating under reduced
pressure and HPLC purification, compound 1g was obtained in
lL l
22 mg). After 4 h the reaction was concentrated. The residue was
18% yield (6 lmol, 8 mg) as a colorless oil.
taken up in DCM (1 mL) and TFA (1 mL) was added. After stirring