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(silica gel; hexane:EtOAc = 15:1) to yield 13c as a yellowish oil (0.89 g,
93%). Rf: 0.20 (hexane:EtOAc = 20:1). 1H NMR (600 MHz, CDCl3): δ
0.88 (t, J = 7.0 Hz, 12H, CH3), 1.20–1.40 (m, 48H, hexyldecyl CH2),
1.61 (m, 2H, hexyldecyl CH), 1.90 (ddd, J = 14.9, 10.5, 2.2 Hz, 1H,
H5a), 2.07 (dd, J = 15.5, 10.6 Hz, 1H, H2a), 2.32 (ddd, J = 15.5, 6.6,
4.7 Hz, 1H, H2e), 2.47 (ddd, J = 14.9, 4.9, 1.7 Hz, 1H, H5e), 2.63 (dt,
J = 6.6, 10.5 Hz, 1H, H3), 2.86 (dt, J = 4.9, 10.4 Hz, 1H, H4), 3.19 (t,
J = 4.2 Hz, 1H, H1), 3.25 (dt, J = 3.7, 1.8 Hz, 1H, H6), 3.93 (ddd, J =
10.8, 5.6, 1.0 Hz, 2H, COOCH2), 4.01 (dt, J = 10.8, 5.8, Hz, 2H,
COOCH2). 13C NMR (150 MHz, CDCl3): δ 14.1 (CH3), 22.7 (CH2), 26.4
(CH2, C2), 26.7 (CH2), 27.2 (CH2, C5), 29.36, 29.61, 29.66, 30.0, 31.15,
31.20, 31.87, 31.94 (CH2), 37.30, 37.32 (CH, hexyldecyl), 37.7 (CH, C4),
40.05 (CH, C3), 50.4 (CH, C1), 51.9 (CH, C6), 67.5 (COOCH2), 173.8,
174.8 (C_O). HRMS: C40H74O5, calcd. m/z [M+H]+ 635.5615, found
635.5583.
40.68 (CH, C1), 40.77 (CH, C2), 51.5 (NCH2, morpholyl), 65.2 (CH, C5),
65.5 (CH, C4), 65.89, 65.95 (COOCH2), 68.2 (OCH2, morpholyl), 176.1,
176.3 (C_O). HRMS: C50H91NO6, calcd. m/z [M+H]+ 802.6925, found
802.6769.
2.2.11. Didodecyl cis-4-hydroxy-trans-5-(2-hydroxyethylamino)cyclohex-
ane-trans-1,2-dicarboxylate (5)
Didodecyl 7-oxabicyclo[4.1.0]heptane-trans-3,4-dicarboxylate 13a
(0.7 g, 1.33 mmol) and 2-aminoethanol (1.6 mL, 26.6 mmol) were
stirred for 72 h at room temperature in 1.1 mL of THF:H2O (10:1). The
reaction mixture was concentrated on the rotary evaporator, and the
crude product was purified by column chromatography (silica gel;
CHCl3:CH3OH = 15:1) to yield 5 as an ivory solid (0.24 g, 30%). Rf:
0.28 (CHCl3:CH3OH = 10:1), mp 55.0–57.0 °C. 1H NMR (600 MHz,
CDCl3): δ 0.84 (t, J = 6.9 Hz, 6H, CH3), 1.18–1.33 (m, 36H, dodecyl
CH2), 1.47 (ddd, J = 13.4, 8.9, 4.5 Hz, 1H, H6a), 1.58 (m, 4H, dodecyl
CH2), 1.67 (ddd, J = 13.8, 9.0, 4.9 Hz, 1H, H3a), 2.20 (ddd, J = 13.6,
4.8, 3.6 Hz, 1H, H3e), 2.27 (ddd, J = 13.5, 4.8, 3.7 Hz, 1H, H6e), 2.48
(dt, J = 3.5, 8.8 Hz, 1H, H5), 2.64 (ddd, J = 12.2, 6.2, 3.7 Hz, 1H,
CH2N), 2.86 (ddd, J = 12.2, 6.4, 3.6 Hz, 1H, CH2N), 3.10 (q, J = 5.0 Hz,
1H, H1), 3.19 (q, J = 5.0 Hz, 1H, H2), 3.50 (dt, J = 3.7, 8.5 Hz, 1H, H4),
3.61 (ddd, J = 10.8, 6.5, 3.8 Hz, 1H, morpholyl CH2O), 3.65 (ddd, J =
10.9, 6.4, 3.7 Hz, 1H, morpholyl CH2O), 4.05 (m, 4H, COOCH2). 13C
NMR (150 MHz, CDCl3): δ 14.1 (CH3), 22.6, 25.85, 25.89 (CH2), 28.3
(CH2, C6), 28.51, 28.56, 29.2, 29.3, 29.49, 29.56, 29.59 (CH2), 31.3
(CH2, C3), 31.9 (CH2), 40.2 (CH, C1+C2), 48.4 (NCH2), 58.65 (CH, C5),
61.45 (OCH2), 65.13, 65.16 (COOCH2), 69.34 (CH, C4), 173.7, 174.0
(C_O). HRMS: C34H65NO6, calcd. m/z [M+H]+ 584.4890, found
584.4933.
2.2.9. Bis[cis-8-(2-octylcyclopropyl)octyl]7-oxabicyclo[4.1.0]heptane-trans-
3,4-dicarboxylate (13d)
Bis[cis-8-(2-octylcyclopropyl)octyl]4-cyclohexene-trans-1,2-
dicarboxylate 12d (2.58 g, 3.7 mmol) was dissolved in anhydr.
CH2Cl2 (5 mL), and m-CPBA (1.36 g of 70% tech. grade, 5.53 mmol)
was added in small portions at 0 °C while stirring. The reaction mix-
ture was stirred at 0 °C for another 18 h. After the consumption of
the starting material (TLC; silica gel; hexane:EtOAc = 20:1), chloroform
(12 mL) was added followed by satd. Na2CO3 (15 mL). The mixture was
stirred for 30 min and then the organic phase was washed with satd.
Na2CO3 (4 × 6 mL). The organic layer was dried for 12 h over anhydrous
Na2SO4 and concentrated in vacuo. The crude product was purified by
column chromatography (silica gel; hexane:EtOAc = 20:1) to yield
13d as a colorless oil (1.64 g, 62%). Rf: 0.24 (hexane:EtOAc = 12:1). 1H
NMR (600 MHz, CDCl3): δ −0.35 (dt, J = 4.2, 5.3 Hz, 2H, trans-H in
cyclopropyl CH2), 0.54 (dt, J = 4.1, 8.2 Hz, 2H, cis-H in cyclopropyl
CH2), 0.63 (m, 4H, cyclopropyl CH), 0.87 (t, J = 7.0 Hz, 6H, CH3), 1.11
(m, 4H, octyl CH2), 1.20–1.39 (m, 48H, octyl CH2), 1.59 (m, 4H, octyl
CH2), 1.88 (ddd, J = 14.9, 10.8, 2.1 Hz, 1H, H5a), 2.04 (dd, J = 15.4,
10.9 Hz, 1H, H2a), 2.30 (ddd, J = 15.5, 6.6, 4.8 Hz, 1H, H2e), 2.45 (ddd,
J = 14.9, 4.9, 1.8 Hz, 1H, H5e), 2.60 (dt, J = 6.7, 10.7 Hz, 1H, H3), 2.82
(dt, J = 4.9, 10.6 Hz, 1H, H4), 3.17 (t, J = 4.3 Hz, 1H, H1), 3.23 (dt, J =
3.7, 1.8 Hz, 1H, H6), 4.04 (m, 4H, COOCH2). 13C NMR (150 MHz,
CDCl3): δ 11.0 (CH2, cyclopropyl), 14.2 (CH3), 15.8 (CH, cyclopropyl),
22.8, 25.95 (CH2), 26.5 (CH2, C2), 27.3 (CH2, C5), 28.64, 28.8, 29.36,
29.45, 29.67, 29.78, 30.27, 30.30, 32.0 (CH2), 37.8 (CH, C4), 40.1 (CH,
C3), 50.4 (CH, C1), 52.0 (CH, C6), 65.0 (COOCH2), 173.8, 174.8 (C_O).
HRMS: C46H82O5, calcd. m/z [M+H]+ 715.6241, found 715.6167.
2.2.12. Didodecyl cis-4-hydroxy-trans-5-(2,2,2-trifluoroethylamino)cyclo-
hexane-trans-1,2-dicarboxylate (7) and didodecyl cis-4-chloro-trans-5-
hydroxycyclohexane-trans-1,2-dicarboxylate (10)
2,2,2-Trifluoroethylamine hydrochloride (1.36 g, 10 mmol) was
neutralized by satd. Na2CO3 to pH 7–8 at 0 °C. Didodecyl 7-
oxabicyclo[4.1.0]heptane-trans-3,4-dicarboxylate 13a (0.52 g, 1 mmol)
in iPrOH (1.5 mL) was added, and the mixture was stirred for 7 days
at 40 °C. The reaction mixture was concentrated on the rotary evapora-
tor, and the crude product was purified by column chromatography (sil-
ica gel; hexane:EtOAc = 5:1) to yield 7 as a yellowish viscous oil (0.1 g,
16%) and 10 as a white solid (0.38 g, 68% yield). Compound 7: Rf 0.25
(hexane:EtOAc = 5:1). 1H NMR (600 MHz, CD3OD): δ 0.89 (t, J =
6.9 Hz, 6H, CH3), 1.23–1.40 (m, 36H, dodecyl CH2), 1.61 (m, 4H, dodecyl
CH2), 1.78 (dt, J = 13.9, 4.0 Hz, 1H, H6e), 1.82 (dt, J = 13.7, 4.1 Hz, 1H,
H3e), 1.95 (m, 1H, H6a), 1.97 (m, 1H, H3a), 2.79 (q, J = 3.8 Hz, 1H, H5),
2.99 (dt, J = 3.7, 9.7 Hz, 1H, H1), 3.03 (dt, J = 4.0, 9.7 Hz, 1H, H2), 3.23
(m, 2H, CH2N), 3.74 (dt, J = 3.2, 4.1 Hz, 1H, H4), 4.06 (m, 4H, COOCH2).
13C NMR (150 MHz, CD3OD): δ 14.5 (CH3), 23.8, 27.1 (CH2), 28.8 (CH2,
C6), 29.8, 30.4, 30.5, 30.71, 30.74, 30.79, 30.83 (CH2), 31.45 (CH2, C3),
33.1 (CH2), 40.43 (CH, C1), 40.74 (CH, C2), 48.86 (CH2N), 58.0 (CH,
C5), 65.9 (COOCH2), 68.7 (CH, C4), 128.2 (CF3), 176.5 (C_O). HRMS:
C34H62F3NO5, calcd. m/z [M+H]+ 622.4658, found 622.4647. Com-
pound 10: Rf 0.50 (hexane:EtOAc = 5:1); mp 31.5–32.5 °C. 1H NMR
(600 MHz, CD3OD): δ 0.90 (t, J = 6.9 Hz, 6H, CH3), 1.24–1.40 (m, 36H,
dodecyl CH2), 1.62 (br. quin, J = 7.0 Hz, 4H, dodecyl CH2), 1.92
(ddd, J = 13.9, 3.4, 2.8 Hz, 1H, H6e), 2.04 (m, 1H, H6a), 2.07 (dt,
J = 14.1, 3.1 Hz, 1H, H3e), 2.28 (m, 1H, H3a), 3.03 (m, 2H,
H1+H2), 3.94 (q, J = 3.2 Hz, 1H, H5), 4.07 (m, 4H, COOCH2), 4.14
(q, J = 3.2 Hz, 1H, H4). 13C NMR (150 MHz, CD3OD): δ 14.5 (CH3),
23.8, 27.0, 29.7 (CH2), 30.4 (CH2, C6), 30.5, 30.70, 30.74, 30.82
(CH2), 31.75 (CH2, C3), 33.1 (CH2), 40.3 (CH, C1), 40.5 (CH, C2),
59.6 (CH, C4), 65.95, 66.06 (COOCH2), 69.5 (CH, C5), 175.7, 176.2
(C_O). HRMS: C32H59ClO5, calcd. m/z [M+H]+ 559.4129, found
559.4136.
2.2.10.
Bis[cis-8-(2-octylcyclopropyl)octyl]cis-4-hydroxy-trans-5-
morpholinocyclohexane-trans-1,2-dicarboxylate (4)
Bis[cis-8-(2-octylcyclopropyl)octyl] 7-oxabicyclo[4.1.0]heptane-
trans-3,4-dicarboxylate 13d (0.47 g, 0.65 mmol) and morpholine
(0.4 mL, 4.6 mmol) were stirred for 5 days at room temperature in
0.6 mL of i-PrOH:H2O (9:1). The reaction mixture was concentrated
on a rotary evaporator. The crude product was purified by column chro-
matography (silica gel; hexane:EtOAc = 9:2) to yield 4 as a colorless oil
(0.44 g, 84%). Rf: 0.23 (hexane:EtOAc = 9:2). 1H NMR (600 MHz,
CD3OD): δ −0.33 (dt, J = 4.1, 5.2 Hz, 2H, trans-H in cyclopropyl CH2),
0.59 (dt, J = 4.1, 8.1 Hz, 2H, cis-H in cyclopropyl CH2), 0.67 (m, 4H,
cyclopropyl CH), 0.90 (t, J = 6.8 Hz, 6H, CH3), 1.19 (m, 4H, octyl CH2),
1.24–1.44 (m, 48H, octyl CH2), 1.62 (br. quin, J = 6.9 Hz, 4H, octyl
CH2), 1.79 (ddd, J = 13.3, 5.0, 4.8 Hz, 1H, H3e), 1.88 (ddd, J = 14.0,
5.3, 3.8 Hz, 1H, H6e), 2.00 (m, 1H, H6a), 2.02 (m, 1H, H3a), 2.24 (dt,
J = 3.0, 5.2 Hz, 1H, H5), 2.50 (m, 2H, CH2N), 2.59 (m, 2H, CH2N), 2.99
(dt, J = 3.5, 9.4 Hz, 1H, H1), 3.09 (dt, J = 4.4, 9.4 Hz, 1H, H2), 3.70 (m,
4H, morpholyl OCH2), 3.99 (dt, J = 2.7, 5.2 Hz, 1H, H4), 4.07 (m, 4H,
COOCH2). 13C NMR (150 MHz, CD3OD): δ 11.6 (CH2, cyclopropyl), 14.5
(CH3), 16.9 (CH, cyclopropyl), 23.8 (CH2), 24.9 (CH2, C6), 27.1, 29.8,
29.9, 30.4, 30.5, 30.7, 30.8, 31.3 (CH2), 31.9 (CH2, C3), 33.1 (CH2),