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135.0 (C, C10), 142.1 (C, C8), 147.1 (C, C5) ppm; MS (ESI+, m/z): derivative 23 in 92% yield. Rf: 0.5 (10% EtOAc/hexane); IR
1
630 [(M + H)+, 100%].
(NaCl): n 2946, 2873, 1758, 1650, 1469 cmꢀ1; H NMR (300.13
1a-[(4-Methoxytetrahydro-2H-pyran-4-yl)oxy]vitamin D3 (17). MHz, CDCl3): d 0.54 (s, 3H, Me18), 0.93 (d, 3H, Me21, J 6.2 Hz),
00
TBAF (120 mL, 0.12 mmol, 1.0 M in THF) was added dropwise to 1.19 (t, 3H, Me3 , J 6.9 Hz), 1.21 (s, 6H, Me26 + Me27), 0.98–2.50
a solution of silyl ether 16 (30 mg, 0.05 mmol) in anhydrous THF (several m, 2H2 + H4ax + H1ax + 2H9 + 2H11 + 2H12 + H14 + 2H15
+
(480 mL) at 0 ꢁC in darkness. The reaction mixture was followed 2H16 + H17 + H20 + 2H22 + 2H23 + 2H24), 2.66 (1H, dd, H4eq, J 13.4,
00
by TLC (5% EtOAc/hexane) until complete consumption of 3.9 Hz), 2.80 (dd, 1H, H1eq, J 11.6, 3.2 Hz), 3.61 (q, 2H, H2 , J 7.1
00
00
starting material (4 h). Then, solvent was evaporated and the Hz), 4.56 (dd, 1H, H3 cis, J 6.2, 2.0 Hz), 4.75 (s, 2H, H1 ), 4.86 (d,
0
mixture was extracted with EtOAc. The combined organic frac- 1H, H19, J 2.0 Hz), 4.88 (m, 1H, H3), 4.90 (dd, 1H, H3 trans, J 13.9,
tions were dried (Na2SO4) and concentrated under vacuum. The 2.0 Hz), 5.07 (d, 1H, H19, J 2.0 Hz), 6.02 (d, 1H, H7, J 11.3 Hz),
0
crude was puried by column chromatography (20% EtOAc/ 6.24 (d, 1H, H6, J 11.4 Hz), 7.10 (dd, 1H, H2 , J 13.8, 6.3 Hz) ppm;
13
00
hexane) to give 17 in 70% yield. Rf: 0.3 (30% EtOAc/hexane);
C NMR (75.5 MHz, CDCl3): d 12.1 (Me18), 15.3 (Me3 ), 19.0
IR (NaCl): n 3269, 2951, 2867, 1467, 1351, 1301 cmꢀ1; H NMR (Me21), 20.7 (CH2), 22.4 (CH2), 23.7 (CH2), 26.5 and 26.6 (Me26
(300.13 MHz, CDCl3): d 0.52 (s, 3H, Me18), 0.86 (2d, 6H, Me26 Me27), 27.8 (CH2), 29.2 (CH2), 31.9 (CH2), 32.0 (CH2), 36.3 (CH,
Me27, J 6.1 Hz), 0.91 (d, 3H, Me21, J 6.2 Hz), 1.00–2.35 (several m,
27H, 2H2 + H4ax + H9ax + 2H11 + 2H12 + H14 + 2H15 + 2H16 + H17
+
1
+
C
C
20), 36.6 (CH2), 40.7 (CH2, C12), 42.0 (CH2), 42.4 (CH2), 46.1 (C,
13), 56.5 and 56.8 (2CH, C17 + C14), 63.1 (CH2, C2 ), 76.3 (C, C25),
00
+
0
0
00
0
H
H
20 + 2H22 + 2H23 + 2H24 + H25 + 2H5 + 2H2 + OH), 2.62 (dd, 1H, 76.7 (CH, C3), 89.7 (CH2, C1 ), 97.7 (CH2, C3 ), 113.2 (CH2, C19),
0
4eq, J 11.5, 3.1 Hz), 2.82 (dd, 1H, H9eq, J 13.1, 3.8 Hz), 3.23 (s, 117.6 (CH, C7), 123.1 (CH, C6), 133.5 (C, C10), 142.8 (CH, C2 ),
3H, H6 ), 3.63 (m, 2H, H3 ), 3.72 (m, 2H, H4 ), 4.23 (m, 1H, H3), 143.0 (C, C8), 144.2 (C5), 152.3 (C]O) ppm; MS (ESI+, m/z): 551
4.51 (m, 1H, H1), 4.76 (s, 1H, OH), 4.97 (d, 1H, H19, J 2.3 Hz), [(M + Na)+, 100%]; HRMS (ESI+, m/z): calcd for C33H52NaO5 (M +
5.27 (d, 1H, H19, J 1.6 Hz), 6.02 (d, 1H, H7, J 11.4 Hz), 6.33 (d, 1H, Na)+: 551.3707, found: 551.3710.
0
0
0
H6, J 11.4 Hz) ppm; 13C NMR (75.5 MHz, CDCl3): d ꢀ12.0 (Me18),
3-O-(tert-Butyldimethylsilyl)-25-(vinyloxycarbonyloxy)vitamin
19.0 (Me21), 22.3 (CH2), 22.7 and 23.0 (Me26 + Me27), 23.7 (CH2), D3 (26). Same procedure as 8. The residue was puried by
0
24.0 (CH2), 27.8 (CH2), 28.2 (CH, C25), 29.1 (CH2), 35.0 (2CH2, C2 column chromatography (4% EtOAc/hexane as eluent) to give
1
0
+ C5 ), 36.2 (CH2), 36.3 (CH, C20), 39.6 (CH2), 40.7 (CH2), 43.1 the derivative 26 in 73% yield; Rf: 0.5 (5% EtOAc/hexane); H
(CH2), 45.8 (CH2), 46.0 (C, C13), 48.7 (CH3), 56.5 (CH, C17), 56.8 NMR (300.13 MHz, CDCl3): d 0.07 (s, 6H, SiMe), 0.54 (s, 3H,
0
0
(CH, C14), 65.20 and 65.23 (CH2, C3 and C4 ), 67.2 (CH, C3), 69.6 Me18), 0.89 (s, 9H, SiCMe3), 0.92 (d, 3H, Me21, J 6.4 Hz), 1.49 (s,
0
(CH, C1), 99.1 (C, C1 ), 112.8 (CH2, C19), 117.3 (CH, C7), 123.8 6H, Me26 + Me27), 0.98–2.50 (several m, 2H2 + 2H4 + H1ax + 2H9 +
(CH, C6), 134.2 (C, C10), 142.9 (C, C8), 147.2 (C, C5) ppm; HRMS 2H11 + 2H12 + H14 + 2H15 + 2H1 + H17 + H20 + 2H22 + 2H23 + 2H24),
(ESI+, m/z): calcd for C33H54O4Na [(M + Na)+]: 537.3914, found: 2.83 (d, 1H, H1eq, J 11.7 Hz), 3.82 (m, 1H, H3), 4.51 (d, H3 , 1H, J
0
0
537.3903.
6.0 Hz) 4.78 (s, 1H, H19), 4.87 (d, 1H, H3 , J 13.9 Hz), 5.00 (s, 1H,
1a-(4-Methoxytetrahydro-2H-pyran-4-yl)oxy-3-O-(vinyloxycar- H19), 6.01 (d, 2H, H7, J 10.5 Hz) 6.16 (d, 2H, H6, J 10.9 Hz), 7.06
bonyl)vitamin D3 (18). Same procedure as 8. The residue was (dd, 1H, H2 , J 13.6, 5.9 Hz) ppm; 13C NMR (75.5 MHz, CDCl3):
0
puried by column chromatography (8% EtOAc/hexane as d ꢀ4.5 (SiMe), ꢀ4.4 (SiMe), 12.3 (Me18), 18.3 (SiC), 18.9 (Me21),
eluent) to give the derivative 18 in 83% yield. Rf: 0.3 (10% 20.6 (CH2), 22.4 (CH2), 23.6 (CH2), 25.8 (Me26 + Me27), 26.1
EtOAc/hexane); IR (NaCl): n 2952, 2867, 2359, 23411657, 1467, (SiCMe3), 27.9 (CH2), 29.1 (CH2), 29.9 (CH2), 32.9 (CH2, C1), 36.2
1
1351, 1260 cmꢀ1; H NMR (300.13 MHz, CDCl3): d 0.52 (s, 3H, (CH, C20), 36.3 (CH2), 36.6 (CH2), 40.7 (CH2, C12), 41.0 (CH2),
Me18), 0.85 (d, 3H, Me26, J 6.6 Hz), 0.87 (d, 3H, Me27, J 6.1 Hz), 45.9 (C, C13), 47.1 (CH2), 56.5 and 56.7 (2CH, C14 + C17), 70.7
0
0.92 (d, 3H, Me21, J 6.2 Hz), 1.00–2.49 (several m, 27H), 2.73 (m, (CH, C3), 86.0 (C, C25), 97.1 (CH2, C3 ), 112.3 (CH2, C19), 118.0
00
00
00
2H, H4eq + H9eq), 3.23 (s, 3H, H6 ), 3.66 (m, 4H, H3 + H4 ), 4.52 (CH, C7), 121.5 (CH, C6), 136.5 (C, C10), 141.6 (C, C8), 142.7 (CH,
+
0
0
0
(m, 1H, H1), 4.57 (dd, 1H, H3 , J 6.2, 2.0 Hz), 4.91 (dd, 1H, H3 , J C2 ), 145.6 (C, C5), 150.9 (C]O) ppm; MS (APCI , m/z): 585 [(M +
13.9, 2.0 Hz), 4.99 (d, 1H, H19, J 2.1 Hz), 5.18 (m, 1H, H3), 5.25 (d, H)+, 50%], 497 [(M ꢀ vinyl carbonate)+, 100%], 365 [(M ꢀ vinyl
1H, H19, J 2.1 Hz), 6.02 (d, 1H, H7, J 11.4 Hz), 6.32 (d, 1H, H6, J carbonate ꢀ OTBDMS)+, 55%]; HRMS (ESI+, m/z): calcd for
0
11.4 Hz), 7.09 (dd, 1H, H2 , J 13.9, 6.2 Hz) ppm; 13C NMR (75.5
MHz, CDCl3): d 11.9 (Me18), 19.0 (Me21), 22.2 (CH2), 22.7, 23.0
C
30H60O4Si [(M + H)+]: 585.4260, found: 585.4246.
3-O-[N-(8-Methoxy-3,6-dioxaoctyl)carbamoyl]vitamin D3 (28).
(Me26 + Me27), 23.7 (CH2), 24.0 (CH2), 27.8 (CH2), 28.2 (CH, C25), A solution of vinyl carbonate 8 (57 mg, 0.12 mmol) in anhydrous
29.2 (CH2), 34.9 (CH2), 35.0 (CH2), 36.2 (CH, C20), 36.3 (CH2), THF (1.7 mL) was treated with 51 mg (0.31 mmol) of 2-[2-(2-
39.5 (CH2), 39.6 (CH2), 40.7 (CH2), 41.8 (CH2), 43.1 (CH2), 46.1 methoxyethoxy)ethoxy]ethylamine and the mixture was stirred
ꢁ
00
00
(C13), 48.7 (Me6 ), 56.5 and 56.8 (2CH, C14 + C17), 65.2 (2CH2, C3
at 50 C until TLC showed complete consumption of starting
00
0
00
+ C4 ), 69.7 (CH, C1), 74.7 (CH, C3), 97.8 (CH2, C3 ), 99.3 (C, C1 ), material (48 h). Then, solvent was evaporated and the residue
113.8 (CH2, C19), 117.1 (CH, C7), 124.6 (CH, C6), 132.2 (C, C10), puried by column chromatography (eluent 40% EtOAc/hexane)
142.7 (CH, C2 ), 143.6 (C, C8), 146.0 (C, C5), 152.2 (C]O) ppm; to afford 28 in 73% yield. Rf: 0.4 (60% EtOAc/hexane); 1H NMR
0
HRMS (ESI+, m/z): calcd for C36H56O6Na [(M + Na)+]: 607.3969, (250.13 MHz, CDCl3): d 0.53 (s, 3H, Me18), 0.85 (d, 6H, Me26
+
found: 607.3956.
Me27, J 6.8 Hz), 0.90 (d, 3H, Me21, J 6.7 Hz), 0.80–3.00 (several m),
0
0
3-O-(Vinyloxy)carbonyl-25-ethoxymethyloxyvitamin D3 (23). 3.37–3.62 (several m, 15H, H2 –8 ), 4.82 (s, 1H, H19), 4.88 (m, 1H,
Same procedure as 8. The residue was puried by column H3), 5.03 (s, 1H, H19), 5.42 (br s, 1H, NH), 6.02 (d, 1H, H7, J 12.4
chromatography (10% Et2O/hexane as eluent) to give the Hz), 6.21 (d, 2H, H6, J 12.0 Hz) ppm; 13C NMR (75.5 MHz,
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RSC Adv., 2016, 6, 31840–31849 | 31847