SONG ET AL.
7
3.3 | tert-Butyl 2,2-dimethyl-4-oxo-
3,8,11,14,17,20,23,26,29,32,35,38,41-tridecaoxa-
5-azatetratetracontan-44-oate (15) and di-
tert-butyl 4-(tert-butoxycarbonyl)-
7,10,13,16,19,22,25,28,31,34,37,40-dodecaoxa-
4-azatritetracontanedioate (16)
(0.5 mL). The solution was stirred at room temperature for
18 hours and then concentrated. Flash chromatography
on silica gel (gradient 0% to 100% EtOAc in heptane) gave
22 (82.6 mg, 87%) as colorless oil. 1H NMR (CDCl3,
400 MHz) δ 7.66 (d, J = 12.6 Hz, 1H), 7.28-7.38 (m, 5H),
5.27 (d, J = 12.6 Hz, 1H), 5.16 (s, 2H), 3.98-4.02 (m, 2H),
3.74-3.78 (m, 2H), 3.63-3.69 (m, 10 H), 3.38 (t, J = 5.1 Hz,
2 H); MS (ES, m/z) 402 (M + Na+).
To
a
solution
of
tert-butyl
(35-hydroxy-3,-
6,9,12,15,18,21,24,27,30,33-undecaoxapentatriacontyl)car-
bamate (14, 229 mg, 0.36 mmol) and tert-butyl acrylate
(46 mg, 0.36 mmol) in CH2Cl2 (1.5 mL) at room tempera-
ture were added Bu4NBr (23 mg, 0.07 mmol) and NaOH
(50 wt% in H2O, 0.1 mL). The mixture was stirred at room
temperature for 3 hours. Water (2 mL) was added, and the
mixture was extracted with CH2Cl2 (2 mL × 4). The com-
bined extracts were washed with H2O (2 mL) and dried
over MgSO4. Filtration and concentration of the filtrate
gave the crude product as colorless oil. Flash chromatogra-
phy on silica gel (gradient EtOAc to 10% MeOH in CH2Cl2)
gave 184 mg of colorless oil, which was a mixture of 15 and
16. Compound 15: 1H NMR (CDCl3, 400 MHz) δ 5.07 (brs,
1H), 3.71 (t, J = 8.0 Hz, 2H), 3.59-3.68 (m, 44H), 3.54 (t, J =
4.0 Hz, 2H), 3.32 (q, J = 4.0 Hz, 2H), 2.50 (t, J = 8.0 Hz,
2H), 1.45 (s, 18H); MS (ES, m/z) 796 (M + Na+). Com-
pound 16: MS (ES, m/z) 925 (M + Na+).
3.6 | Benzyl (E)-3-oxo-1-phenyl-
2,7,10,13,16-pentaoxa-4-azanonadec-17-en-
19-oate (23)
To a stirred solution of benzyl propiolate (18, 30 mg,
0.19 mmol) in CH2Cl2 (1 mL) at room temperature were
added benzyl (2-(2-(2-(2-hydroxyethoxy)ethoxy)ethoxy)
ethyl)carbamate (20, 93 mg, 0.29 mmol) and N-
methylmorpholine (29 mg, 0.29 mmol). The solution was
stirred at room temperature for 3.5 hours and then concen-
trated. Flash chromatography on silica gel (gradient 0% to
100% EtOAc in heptane) gave 23 (75.7 mg, 82%) as color-
less oil. 1H NMR (CDCl3, 400 MHz) δ 7.63 (d, J = 12.1 Hz,
1H), 7.26-7.38 (m, 10H), 5.31 (brs, 1H, NH), 5.25 (d, J =
12.1 Hz, 1H), 5.15 (s, 2H), 5.09 (s, 2H), 3.91-3.98 (m, 2H),
3.67-3.74 (m, 2H), 3.58-3.66 (m, 8 H), 3.55 (t, J = 5.1 Hz,
2 H), 3.39 (q, J = 5.2 Hz, 2H); MS (ES, m/z) 488 (M + H+).
3.4 | Benzyl (E)-2,2-dimethyl-4-oxo-
3,8,11,14,17-pentaoxa-5-azaicos-18-en-
20-oate (21)
3.7 | Benzyl (E)-2,2-dimethyl-4-oxo-
3,8,11,14,17,20,23,26,29,32,35,38,41-tridecaoxa-
5-azatetratetracont-42-en-44-oate (24)
To a stirred solution of benzyl propiolate (18, 400 mg,
2.5 mmol) in CH2Cl2 (15 mL) were added tert-butyl
(2-(2-(2-(2-hydroxyethoxy)ethoxy)ethoxy)ethyl)carbamate
(11, 1.099 g, 3.75 mmol) and N-methylmorpholine
(379 mg, 3.75 mmol). The solution was stirred at room
temperature for 18 hours and then concentrated. Flash
chromatography on silica gel (gradient 0% to 100% EtOAc
To a stirred solution of benzyl propiolate (18, 52 mg,
0.33 mmol) in CH2Cl2 (1 mL) at room temperature were
added
tert-butyl
(35-hydroxy-3,-
6,9,12,15,18,21,24,27,30,33-undecaoxapentatriacontyl)car-
bamate (14, 210 mg, 0.33 mmol) and N-methylmorpholine
(49 mg, 0.49 mmol). The solution was stirred at room tem-
perature for 5 hours and then concentrated. Flash chroma-
tography (gradient CH2Cl2 to 10% MeOH in CH2Cl2) gave
24 (229.7 mg, 88%) as colorless oil. 1H NMR (CDCl3,
400 MHz) δ 7.66 (d, J = 12.6 Hz, 1H), 7.28-7.39 (m, 5H),
5.27 (d, J = 12.6 Hz, 1H), 5.16 (s, 2H), 5.06 (brs, 1H, NH),
3.97-4.02 (m, 2H), 3.73-3.78 (m, 2H), 3.57-3.73 (m, 40 H),
3.54 (t, J = 5.1 Hz, 2 H), 3.26-3.35 (m, 2H); MS (ES, m/z)
828 (M + Na+).
1
in heptane) gave 21 (1.007 g, 89%) as colorless oil. H
NMR (CDCl3, 400 MHz) δ 7.66 (d, J = 12.6 Hz, 1H),
7.29-7.38 (m, 5H), 5.27 (d, J = 12.6 Hz, 1H), 5.16 (s, 2H),
5.01 (brs, 1H, NH), 3.98-4.04 (m, 2H), 3.74-3.79 (m, 2H),
3.58-3.71 (m, 8 H), 3.53 (t, J = 5.1 Hz, 2 H), 3.27-3.35 (m,
2H), 1.44 (s, 9H); MS (ES, m/z) 476 (M + Na+).
3.5 | Benzyl (E)-1-azido-
3,6,9,12-tetraoxapentadec-13-en-15-oate (22)
3.8 | 2,2-Dimethyl-4-oxo-
3,8,11,14,17-pentaoxa-5-azaicosan-20-oic
acid (25)
To a mixture of 2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)
ethan-1-ol (7, 66 mg, 0.3 mmol) and N-methylmorpholine
(30 mg, 0.3 mmol) in CH2Cl2 (0.5 mL) was added a solu-
tion of benzyl propiolate (18, 40 mg, 0.25 mmol) in CH2Cl2
A mixture of compound 21 (985 mg, 2.17 mmol) and
Pd/C (10 wt%, 231 mg, 0.22 mmol) in 30 mL of THF was