C. Alexenberg, et al.
ChemistryandPhysicsofLipids221(2019)128–139
data. The NMR reveals varying amounts of lysoPC 13.
186–188 ºC; 1H NMR (CDCl3) δ 5.21 (m, 1H, H2), 4.37 (m, 1H, H1b),
4.28 (m, 2H, H4), 4.13 (m, 1H, H1a), 4.00 (m, 2H, H14′′), 3.89 (m. 2H,
H3), 3.79 (m, 2H, H5), 3.38 (s, 9H, H6), 2.29 (2 ”t”, J = 7 Hz, 4H, H2′
and H2′′), 1.81 (m, 4H, H13′′ and H15′′), 1.58 (m, 8H, H3′, H3′′ and H12′′),
1.26 (m, 44H, methylenes: H4′–H15′, H4′′–H11′′ and H16′′–H17′′), 0.88 (2
”t”, J = 7, 6H, H16′ and H18′′). 13C NMR (CDCl3) δ 173.57 and 173.21
(C1′ and C1′′), 70.29 (d, Jcp = 6.5 Hz, C4), 66.41 (d, Jcp = 3 Hz, C5),
63.90 (d, Jcp = 3 Hz, C2), 62.80 (C1), 59.72 (C3), 58.94 (C14′′), 54.61
(C6), 39.23 and 39.93 (C13′′ and C15′′), 34.34 and 34.16 (C2′ and C2′′),
31.95 (C14′), 29.74, 29.69, 29.64, 29.58, 29.56, 29.39, 29.22, 29.19 and
29.13 (methylenes: C4′–C13′ and C4′′–C11′′), 27.63 (C12′′ and C16′′), 24.99
and 24.93 (C3′ and C3′′), 22.71 and 22.20 (C15′ and C17′′), 14.124 and
13.971 (C16′ and C18′′). MS (TOF-ES+) m/z: 842.52 (MH++2, 97.6%),
2.3.4.1. 1-Palmitoyl-2-(2′′-bromopalmitoyl)-sn-glycero-3-
phosphatidylcholine (14a). 74% yield, Phase Transition Temp. (melt):
172–174 °C; 1H NMR (CDCl3) δ 5.28 (m, 1H, H2), 4.40 (m, 1H, H1b),
4.27 (m, 2H, H4), 4.21 (m, 1H, H1a), 4.08 (m, 1H, H2′′), 3.99 (m, 2H,
H3), 3.86 (m, 2H, H5), 3.37 (s, 9H, H6), 2.26 (m, 2H, H2′), 1.96 (m, 2H,
H3′′), 1.58 (m, 2H, H3′), 1.29 (m, 48H, methylenes: H4′–H15′ and
H4′′–H15′′), 0.88 (”t”, J = 7 Hz, 6H, H16′ and H16′′). 13C NMR (CDCl3)
δ 173.85 and 169.54 (C1′ and C1′′), 72.18 (d, Jcp = 7.5 Hz, C4), 66.89
(d, Jcp =6.5 Hz, C5), 63.76 (d, Jcp =3 Hz, C2), 62.46 (C1), 59.83 (d, Jcp
=3 Hz, C3), 54.56 (C6), 45.80 (C2′′), 34.96 (C2′ and C3′′), 31.93 (C14′ and
C14′′), 29.73, 29.68, 29.63, 29.57, 29.46, 29.37, 29.29, 29.23, 28.97
and 28.81 (methylenes: C4′–C13′ and C5′′–C13′′), 27.26 (C4′′), 24.87 (C3′),
22.68 (C15′ and C15′′), 14.09 (C16′ and C16′′). MS (TOF-ES+) m/z:
814.48 (MH++2, 99.1%), 812.48 (MH+ 100%), 496.32 (MH+-CO-
840.51 (MH+
, 100%). HRMS (MALDI matrix DHB) m/z calc.
(C42H8479BrNO8P, MH+) 840.5112, obsd. 840.5110. FTIR 2921 and
2854 (s), 1748 (w, C]O), 1648 (s), 1548 and 1479 (w), 1237 (w,
C
15H30Br, 71.9%). HRMS (MALDI matrix THAP) m/z calc.
CeO,P]O), 1086 (s), 864 (w, PeOeR), 813 (w, CeBr) cm−1
.
(C40H8079BrNO8P, MH+) 812.4740, obsd. 812.4799. FTIR 2916 and
2850 (s), 1733 (m, C]O) 1473 (m), 1240 (m, CeO and P]O), 1062 (s),
2.4. Synthesis of n-iodophospholipids 17a–d:
865 (w, PeOeR-ester), 814 (w, CeBr) cm−1
.
The synthesis of n-iodophospholipids 17a–d begins, along the same
lines as for the corresponding bromophospholipids, from n-ketoesters
9b–d (through n-hydroxystearate esters 10b–d) or commercially
2.3.4.2. 1-Palmitoyl-2-(6′′-bromostearoyl)-sn-glycero-3-
phosphatidylcholine (14b). 71% yield. Phase Transition Temp (melt):
167–169 °C; 1H NMR (CDCl3) δ 5.20 (m, 1H, H2), 4.39 (m, 1H, H1b),
4.30 (m, 2H, H4), 4.11 (m, 1H, H1a), 4.00 (m, 1H, H6′′), 3.94 (m, 2H,
H3), 3.75 (m, 2H, H5), 3.32 (s, 9H, H6), 2.39 (m, 6H, H2′,H2′′ and H5′′),
1.80 (m, 10H, H3′, H3′′, H4′′, H7′′ and H8′′), 1.57 (m, 8H, H4′, H5′, H9′′ and
H10′′), 1.26 (m, 34H, methylenes: H6′–H15′ and H11′′–H17′′), 0.88 (”t”,
J = 7 Hz, 6H, H16′ and H18′′). 13C NMR (CDCl3) δ 173.66 and 172.97
(C1′ and C1′′), 70.63 (d, Jcp = 7 Hz, C4), 66.43 (d, Jcp = 5.5 Hz, C5),
63.51 (d, Jcp =4 Hz, C2), 62.59 (C1), 59.36 (d, Jcp =4 Hz, C3), 58.59
(C6′′), 54.49 (C6), 39.38 and 38.87 (C5′′ and C7′′), 34.17 and 34.13 (C2′
and C2′′), 31.95 (C14′ and C16′′), 30.94, 29.77, 29.71, 29.66, 29.63,
29.59, 29.40, 29.25, 29.16 and 29.06 (methylenes: C4′-C13′ and
C9′′–C15′′), 27.70 and 27.21 (C4′′ and C8′′), 24.93 and 24.35 (C3′ and
C3′′), 22.71 (C15′ and C17′′), 14.14 (C16′ and C18′′). MS (TOF-ES+) m/z:
842.51 (MH++2, 100%), 840.51 (MH+ 89.5%), 496.32 (MH+−CO-
2.4.1. Preparation of iodostearate esters 15b–d
Iodooesters 15b–d were prepared from the corresponding hydro-
xyesters 10b–d with triphenylphospine and iodine according to the
(1) the reaction was carried out under dryness conditions; (2) the re-
action was carried out in dry chloroform (not dichloromethane); (3)
The iodine was added in ice water bath to the flask with the hydro-
xystearate (1 equivalent.) and imidazole (2.3 equivalents), in several
portions during a course of 2 h.; (4) the reaction was run at r.t. over-
night; (5) the reaction was quenched by saturated sodium thiosulfate,
distilled water and ether, dried, and purified by extraction into cold
hexane – to give the pure iodide esters as a yellow oil.
C
17H34Br, 81.6%). HRMS (MALDI matrix DHB) m/z calc.
(C42H8479BrNO8P,MH+) 840.5112, obsd. 840.5050. FTIR 2920 (s),
2.4.1.1. Methyl 6-iodostearate (15b). 46% yield; 1H NMR (CDCl3) δ
4.01 (septet, J =4 Hz, 1H, H6), 3.57 (s, 3H, OCH3), 2.25 (t, J = 7.5,
2 H Hz, H2), 1.78 (m, 2H, H5), 1.66–1.29 (m, 8H, H3–H4 and H7–H8),
1.19 (m, 18H, H9- H17, methylenes), 0.81 (”t”, J = 7 Hz, 3H, H18). 13C
NMR (CDCl3): δ 172.63 (C1), 50.41 (OCH3), 39.71 and 39.27 (C5 and
C7), 38.37 (C6), 32.83 (C2), 30.97 (C16), 28.76, 28.72, 28.70, 28.64,
28.56, 28.54 and 28.41 (methylenes: C9-C15), 28.10 and 27.90 (C4 and
C8), 23.15 (C3), 21.73 (C17), 13.16 (C18). MS (TOF-ES+) m/z: 447
2852 (s), 1737 (m, C]O) 1477 (m), 1237 (m, CeO and P]O) and
1062 (s), 866 (w, P-O-R-ester) 816 (w, CeBr) cm−1
.
2.3.4.3. 1-Palmitoyl-2-(10′′-bromostearoyl)-sn-glycero-3-
phosphatidylcholine (14c). 46% yield, Phase Transition Temp (melt):
177–179 °C; 1H NMR (CDCl3) δ 5.19 (m, 1H, H2), 4.40 (m, 1H, H1b),
4.38 (m, 2H, H4), 4.10 (m, 1H, H1a), 4.01 (m, 1H, H10′′), 3.92 (m, 2H,
H3), 3.77 (m, 2H, H5), 3.33 (s, 9H, H6), 2.27 (2′'t”, J = 7.5 Hz, 4H, H2′
and H2′′), 1.79 (m, 4H, H9′′ and H11′′), 1.57 (m, 8H, H3′, H3′′, H8′′ and
H12′′), 1.26 (m, 42H, methylenes: H4′–H15′, H4′′–H7′′ and H13′′–H17′′),
0.88 (2′'t”, J = 6, 6H, H16′ and H18′′). 13C NMR (CDCl3) δ 173.63 and
173.27 (C1′ and C1′′), 70.54 (d, Jcp =4 Hz, C4), 66.47 (d, Jcp =5.5 Hz,
C5), 63.58 (d, Jcp =4.5 Hz, C2), 63.03 (C1), 59.39 (d, Jcp =4 Hz, C3),
58.95 (C10′′), 54.504 (C6), 39.29 and 39.26 (C9′′ and C11′′), 34.33 and
34.18 (C2′ and C2′′), 31.96 and 31.88 (C14′ and C16′′), 29.77, 29.71,
29.63, 29.49, 29.45, 29.40, 29.34, 29.27, 29.22 and 29.13 (methylenes:
C4′–C13′, C4′′–C7′′ and C13′′–C15′′), 27.65 (C8′′ and C12′′), 24.98 and 24.94
(C3′ and C3′′), 22.71 and 22.68 (C15′ and C17′′), 14.13 and 14.11 (C16′
and C18′′). MS (TOF-ES+) m/z: 842.52 (MH++2, 94.4%), 840.51
(MH+, 100%), 496.35 (MH+-CO-C17H34Br, 78.9%). HRMS (MALDI
matrix DHB) m/z calc. (C42H8479BrNO8P, MH+) 840.5112, obsd.
840.5110. FTIR 2927 and 2859 (s), 1748 and 1725 (w, C]O), 1548
and 1486 (w), 1236 (w, CeO, P]O), 1086 (s), 864 (w, PeOeR), 813
, ,
(MNa+ 100%), 319 (MNa+-HI, 27.52%), 279 (MNa+-C12H24
41.12%); anal. HRMS (ESI): calcd (C19H37O2I, M+) 424.182, obsd.
424.184. FTIR 2921 (s), 2852 (s), 1739 (s, C]O), 1436 (m), 1169 (s,
CeO), 721 (m, CeI) cm−1
.
2.4.1.2. Methyl 10-iodostearate (15c). 46% yield; 1H NMR (CDCl3)
δ 4.11 (septet, J =4 Hz, 1H, H10), 3.67 (s, 3H, OCH3), 2.30 (t,
J = 7.5 Hz, 2H, H2), 1.85 (m, 2H, H9), 1.68 (m, 2H, H11), 1.62 (m,
2H, H3), 1.52 (m, 2H, H8), 1.39 (m, 2H, H12), 1.30 (m, 18H,
methylenes: H4–H7 and H13–H17), 0.88 (”t”, J = 7 Hz, 3H, H18). 13C
NMR (CDCl3): δ 174.29 (C1), 51.45 (OCH3), 40.70 and 40.68 (C9 and
C
11), 40.64 (C10), 34.10 (C2), 31.86 (C16), 29.54, 29.50, 29.45, 29.32,
29.26, 29.17 and 29.10 (methylenes: C4–C7 and C13–C15), 28.87 and
28.78 (C8 and C12), 24.93 (C3), 22.665 (C17), 14.11 (C18). MS (TOF-ES
+) m/z: 447 (MNa+, 100%), 335 (MNa+-C8H17+H+, 3.65%), 319
(MNa+-HI, 11.1%); anal. HRMS (ESI): calcd (C19H37O2I, M+) 424.182,
obsd. 424.184. FTIR 2923 and 2853 (s), 1739 (s, C]O), 1435 (m), 1169
(w, CeBr) cm−1
.
(m, CeO), 720 (m, CeI) cm−1
.
2.3.4.4. 1-Palmitoyl-2-(14′′-bromostearoyl)-sn-glycero-3-
phosphatidylcholine (14d). 80% yield. Phase Transition Temp (melt):
2.4.1.3. Methyl 14-iodostearate (15d). 65% yield; 1H NMR (CDCl3)
132