The Journal of Organic Chemistry
Article
Synthesis of Compound 5a (DA2).
RBF, DMF was added and stirred for 12 h at RT. Upon
completion, water was added to the reaction mixture and
extracted thrice with ethyl acetate. The combined organic layer
was dried over Na2SO4 and concentrated under vacuum to get a
crude product. The obtained crude product was purified by silica
gel column chromatography using ethyl acetate/hexane as an
eluent, (Rf = 0.6, solvent = 50% ethyl acetate/hexane) to get
1
yellow colored liquid (30 mg, 90%). H NMR (400 MHz,
CDCl3): 6.62−6.35 (m, 9H), 4.94 (s, 4H), 4.50 (s, 2H), 3.93 (t,
J = 6.4 Hz, 8H), 3.71−3.53 (m, 14H), 3.36 (t, J = 4 Hz, 2H),
1.80−1.73 (m, 8H), 1.48−1.25 (m, 30H), 0.90 (t, J = 6.4 Hz,
12H). 13C NMR {1H} NMR (100 MHz, CDCl3): δC 160.6,
160.2, 140.9, 139.4, 106.7, 105.9, 101.3, 100.9, 73.3, 70.8, 70.2,
69.5, 68.2, 50.8, 31.7, 29.8, 29.2, 25.7, 22.8, 14.2. HRMS (ESI−
TOF) m/z: [M + Na] calcd for C53H83N3O10Na, 944.5976;
found, 944.5977.
Synthesis and characterization data of compound 5a were
previously reported by our group.14 1H NMR (400 MHz,
CDCl3): δH 6.60 (d, J = 2 Hz, 2H), 6.55−6.53 (m, 5H), 6.40 (t, J
= 2 Hz, 2H), 4.95 (s, 4H), 4.62 (s, 2H), 3.93 (t, J = 6.8 Hz, 8H),
1.764 (quint, J = 6.8 Hz, 8H), 1.48−1.41 (m, 8H) 1.13−1.29 (m,
16H) 0.91 (t, J = 6.8 Hz, 12H); 13C NMR {1H} NMR (100
MHz, CDCl3): δC 160.6, 160.3, 143.5, 139.1, 105.9, 101.5,
105.9, 70.3, 68.2, 65.6, 31.7, 29.4, 25.8, 22.7, 14.4; MALDI−
TOF MS (M + K+): 784.46 (C45H68O7 + K+ calculated 784.46).
Synthesis of Compound 5b.
Synthesis of Compound 1l.
Synthesis and characterization of compound 1l was previously
reported by our group.13 1H NMR (400 MHz, D2O): δH 4.19−
4.02 (m, 4H), 3.78−3.55 (m, 31H), 2.17−2.08 (m, 4H), 1.31 (t,
J = 7.2 Hz, 6H). 13C NMR {1H} NMR (100 MHz, D2O): δC
70.7, 70.6, 70.4, 70.6, 70.5, 70.2, 70.1, 65.2, 50.7, 27.8, 26.4, 16.4.
Synthesis of Compound 1j.
In an oven-dried RBF, compound 5a (100 mg, 0.138 mmol) was
dissolved with stirring in THF. Sodium hydride (NaH) (6.6 mg,
0.277 mmol) was added to a flask in small portions at 0 °C. After
1 h, ditosyl TEG (138 mg, 0.276 mmol) was added dropwise,
maintaining the reaction at the same temperature. Then, the
reaction was stirred for 12 h at RT. Upon completion, excess
NaH was quenched with the dropwise addition of water. The
resulting reaction mixture was extracted in DCM thrice. The
combined organic layer was dried over Na2SO4 and concen-
trated under vacuum. The obtained crude product was purified
by silica gel column chromatography using ethyl acetate/hexane
as an eluent, (Rf = 0.46, solvent = 50% ethyl acetate/hexane) to
In an oven-dried RBF, the above-obtained activated ester of
clyclooctatrine (1.1 equiv) and compound 1l (1 equiv) were
dissolved in DMF under stirring. Then, Et3N (1.1 equiv) was
added slowly to the reaction mixture and stirred at RT for 12 h.
Upon the completion of the reaction, DMF and Et3N were
evaporated under vacuum. To the obtained residue, water was
added and extracted thrice with DCM. The combined organic
layer was dried over Na2SO4 and concentrated under vacuum to
get the crude product, which was purified by silica gel column
1
get yellow colored liquid (58 mg, 40%). H NMR (400 MHz,
CDCl3): δH 7.77 (d, J = 8 Hz, 2H), 7.31 (d, J = 8 Hz, 2H), 6.60−
6.40 (m, 10H), 4.93 (s, 4H), 4.50 (s, 2H), 4.13 (t, J = 6 Hz, 2H),
3.93 (t, J = 8 Hz, 8H), 3.71−3.52 (m, 16H), 2.43 (s, 2H), 1.79−
1.72 (m, 12H), 1.48−1.19 (m, 28H), 0.9 (t, J = 8 Hz, 12H). 13C
NMR {1H} NMR (100 MHz, CDCl3): δC 160.8, 160.2, 145.1,
139.1, 133.1, 130.0, 128.3, 106.7, 105.9, 101.2, 100.9, 73.1, 70.8,
70.6, 70.2, 69.4, 69.1, 68.9, 68.6, 68.2, 31.7, 29.4, 26.0, 22.7, 14.2.
HRMS (ESI−TOF) m/z: [M + Na] calcd for C60H90O13SNa,
1073.6000; found, 1073.5997.
1
chromatography using MeOH/DCM as an eluent. H NMR
(400 MHz, CDCl3): δH 4.23 (m, 4H), 3.60−3.40 (m, 27H),
2.46 (m, 2H), 2.22 (m, 2H), 1.63 (m, 14H). MALDI−TOF MS:
calcd for C31H56NO12P + Na, 688.61; found, 688.63.
Synthesis of Compound 1k.
Synthesis of Compound 5c (DA1).
In an oven-dried RBF, the above-obtained compound 1j (1
equiv) was taken, and LiBr (20 equiv) was added. To the
mixture, DMF was added and heated at 95 °C for 20 h. Upon
completion, water was added and extracted thrice with ethyl
acetate. The water layer was collected, and 2N HCl was added
and stirred for another 30 min. The mixture was then extracted
thrice with ethyl acetate. The combined organic layer was dried
over Na2SO4 and concentrated under vacuum to get the crude
product, which was used without purification.
To the mixture of compound 5a (40 mg, 0.04 mmol) and
sodium azide (NaN3) (9.0 mg, 0.06 mmol) in an oven-dried
8587
J. Org. Chem. 2021, 86, 8576−8589