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Organic & Biomolecular Chemistry
Page 14 of 17
DOI: 10.1039/C7OB00458C
ARTICLE
Journal Name
H-16a), 2.06−1.93 (m, 6H, H-15a, H-7a, H-12a), 1.65−1.33 (m, 12H, 6), 26.6 (C-7), 26.0 (C-11), 21.7 (C-15), 14.0 (C-18) ppm; HRESI-MS
H-15b, H-8, H-11b, H-14, H-12b, H-7b), 0.91 (s, 6H, CH3-18) ppm; m/z calcd for C21H26NO280Se ([M+H]+): 404.1123, found: 404.1117.
13C-NMR (125.7 MHz, CDCl3) δ 221.0 (C-17), 156.5 (C-3), 138.0 (C-5),
132.6 (C-10), 126.5 (C-1), 114.9 (C-4), 111.4 (C-2), 67.9 (CH2Se), 50.5
(C-14), 48.1 (C-13), 44.1 (C-9), 38.5 (C-8), 36.0 (C-16), 31.7 (C-12), yl]diselenide 48. Compound 47 (0.13 g, 0.086 mmol) was dissolved
29.8 (C-6), 28.4 (CH2Se), 26.6 (C-7), 26.0 (C-11), 21.7 (C-5), 14.0 (C- in a 3:1:1 TFA THF H2O mixture (8 ml) and the reaction was kept
18) ppm; HRESI-MS m/z calcd for C40H50NaO480Se2 ([M+Na]+): stirring at rt for 2 h; after that, it was neutralized with a sat. aq.
Bis[(25R)- 16β-Acetoxy- 3β-hydroxy-22-oxocholest-5-en-26-
−
−
777.1932, found: 777.1910.
NaHCO3 solution, and diluted with CH2Cl2. The organic layer was
separated, washed with brine, dried over MgSO4 and filtrated; the
filtrate was concentrated to dryness and purified by column
General procedure for the preparation of selenoureas 39, 40
To a solution of 3-(2’-aminoethoxy)estra-1,3,5(10)-trien-17-one 38 chromatography (3:2 hexane-EtOAc) to give 48 as a yellow oil. Yield:
ꢀ ꢁꢃꢅ
(60.0 mg, 0.19 mmol) in CH2Cl2 (5 mL) was added the corresponding 30 mg, 33%. α
+17 (c 0.2, CHCl3). 1H-NMR (500 MHz, CDCl3) δ
ꢂ
isoselenocyanate (3.0 equiv.), and the reaction was kept at rt, under 5.32 (m, 1H, H-6), 4.95 (ddd, 1H, J15ax,16= 4.9 Hz, J16,17= J15eq,16 = 8.1
Ar and in the dark during the time indicated in each case. After that, Hz, H-16), 3.51 (m, 1H, H-3), 2.96 (dd, 1H, J25,26a= 5.6 Hz, J26a,26b
it was concentrated to dryness, and the residue was purified by 12.0 Hz, H-26a), 2.94 (m, 1H, H-20), 2.80 (dd, 1H, J25,26b= 7.3 Hz, H-
column chromatography (4:1 cyclohexane EtOAc). 26b), 2.62 (ddd, 1H, J23a,24a= 10.4 Hz, J23a,24b= 5.4 Hz, J23a,23b= 17.8 Hz,
3-[2´-(3´´-p-Tolylselenoureido)ethoxy]estra-1,3,5(10)-trien-17- H-23a), 2.39 (m, 1H, H-15a), 2.34 (ddd, 1H, J23b,24b= 10.1 Hz, J23b,24a
=
−
=
one 39. p-Tolyl isoselenocyanate (113.1 mg, 0.58 mmol) was used, 5.0 Hz, H-23b), 2.28 (m, 1H, H-4a), 2.22 (m, 1H, H-4b), 1.95 (s, 3H,
ꢀ ꢁꢃꢄ
and the reaction took place for 4 h. Yield: 29.5 mg, 30%. α
+51 OC(O)CH3), 1.92 (m, 1H, H-2a), 1.92 (m, 1H, H-12eq), 1.89 (m, 1H, H-
ꢂ
1
(c 0.95, CH2Cl2); H-NMR (300 MHz, CDCl3) δ 8.10 (brs, 1H, Ar-NH), 17), 1.82 (m, 1H, H-7a), 1.82 (m, 1H, H-1a), 1.72 (m, 1H, H-24a), 1.71
7.19 (m, 4H, Ar-H), 7.07 (d, 1H, J1,2= 8.2 Hz, H-1), 6.74 (brs, 1H, CH2- (m, 1H, H-25), 1.53 (m, 1H, H-11a), 1.52 (m, 1H, H-2b), 1.51 (m, 1H,
NH), 6.62 (dd, 1H, J2,4 = 2.6 Hz, H-2), 6.56 (d, 1H, H-4), 4.13 (m, 4H, H-8), 1.46 (m, 1H, H-7b), 1.46 (m, 1H, H-11b), 1.37 (m, 1H, H-24b),
H-1´, H-2´), 2.87 (m, 2H, H-6a,H-6b), 2.50 (dd, 1H, J15,16a= 8.4 Hz, 1.26 (ddd, 1H, J11eq,12ax= 4.0 Hz, J12ax,12eq= J11ax,12ax= 12.6 Hz, H-12ax),
J16a,16b = 18.3 Hz, H-16a), 2.40
Ar), 2.24 (m, 1H, H-9), 2.14 (dt, 1H, J15a,16b=J15b,16b=8.9 Hz, H-16b), H-15b), 1.0 (m, 1H, H-14), 0.99 (s, 3H, CH3-19), 0.97 (d, 3H, J25,27
2.08 1.92 (m, 3H, H-15a, H-7a, H-12a), 1.63
1.47 (m, 6H, H-15b, H- 6.5 Hz, CH3-27), 0.95 (m, 1H, H-9), 0.85 (s, 3H, CH3-18); 13C-NMR
−2.35 (m, 1H, H-11a), 2.37 (s, 3H, CH3- 1.12 (d, 3H, J20,21= 7.1 Hz, CH3-21), 1.08 (m, 1H, H-1b), 1.01 (m, 1H,
=
−
−
8, H-14, H-12b, H-11b, H-7b), 0.90 (s, 3H, CH3-18) ppm; 13C-NMR (125.7 MHz, CDCl3) δ 213.0 (C-22), 170.0 (OC(O)CH3), 140.8 (C-5),
(125.7 MHz, CDCl3) δ 220.9 (C-17), 179.3 (CSe), 156.4 (C-3), 138.3 121.4 (C-6), 75.9 (C-16), 71.7 (C-3), 55.1 (C-17), 54.0 (C-14), 49.9 (C-
(C-5), 138.1 (Ar-C-ipso), 133.0 (C-10), 132.9 (Ar-C-p), 131.1 (Ar-C-m), 9), 43.6 (C-20), 42.3 (C-4), 41.9 (C-13), 39.7 (C-12), 38.9 (C-26), 38.8
126.7 (C-1), 125.4 (Ar-C-o), 114.5 (C-4), 112.5 (C-2), 66.5 (CH2O), (C-23), 37.2 (C-1), 36.5 (C-10), 34.9 (C-15), 34.0 (C-25), 31.7 (C-2),
50.5 (C-14), 48.1 (C-13), 47.7 (CH2N), 44.1 (C-9), 38.5 (C-8), 36.0 (C- 31.6 (C-7), 31.3 (C-8), 29.9 (C-24), 21.4 (OAc), 20.8 (C-11), 19.6 (C-
16), 31.7 (C-12), 29.8 (C-6), 26.6 (C-7), 26.1 (C-11), 21.7 (C-15), 21.2 19), 19.5 (C-27), 16.9 (C-21), 13.4 (C-18); HRESI-MS calcd for
(CH3-Ar), 14.0 (C-18) ppm; HRESI-MS m/z calcd for C58H90NaO880Se2 ([M+Na]+): 1097.4858, found: 1097.4862.
C28H34N2NaO280Se ([M+Na]+): 533.1678, found: 533.1662.
3-(2’-Isoselenocyanatoethoxy)estra-1,3,5(10)-trien-17-one 42.
[(25R)-3β,16β-Dihydroxy-22-oxocholest-5-en-26-
A solution of triphosgene (119 mg, 0.40 mmol) in dry CH2Cl2 (10 mL) yl]selenocyanate 51. KSeCN (0.15 g, 1.01 mmol) was added, under
was dropwise added (roughly 1 h) over a refluxing solution of 3-(2’- Ar, to a solution of 50 (0.12 g, 0.20 mmol) in dry THF (7 mL). The
formamidoethoxy)estra-1,3,5(10)-trien-17-one 41 (102.8 mg, 0.30 mixture was refluxed during 9.5 h in the dark, and after that it was
mmol) and Et3N (0.46 mL, 3.30 mmol) in dry CH2Cl2 (10 mL) under concentrated to dryness. Column chromatography (4:1
Ar. After the addition, the corresponding mixture was refluxed hexane EtOAc) afforded 51 as a colorless oil. Yield: 89 mg, 87%.
−
14 (c 1.12, CH2Cl2); 1H-NMR (500 MHz, CDCl3) δ 5.33 (m, 1H,
ꢀ ꢁꢃꢊ
ꢂ
−
during 2.5 h; then, selenium black (188 mg, 2.38 mmol) was added
ꢉ
and the mixture was refluxed overnight. After that, it was filtrated H-6), 4.33 (ddd, 1H, J16,17= J15eq,16= 7.8 Hz, J15ax,16= 4.6 Hz, H-16), 3.50
over a Celite® pad, the filtrate was concentrated to dryness and the (m, 1H, H-3), 3.14 (dd, 1H, J26a,25= 5.6 Hz, J26a,26b= 12.0 Hz, H-26a),
residue was purified by column chromatography (cyclohexane→7:3 2.90 (dd, 1H, J25,26b= 7.4 Hz, H-26b), 2.28 (m, 1H, H-4a), 2.23 (m, 1H,
ꢀ ꢁꢃꢆ
+50 (c 1.17, H-15eq), 2.22 (m, 1H, H-4b), 1.99 (ddd, 1H, J11ax,12eq= J11eq,12eq= 3.6
cyclohexane
−
EtOAc). Yield: 20.3 mg, 17%.
α
ꢂ
1
CH2Cl2); H-NMR (500 MHz, CDCl3) δ 7.22 (d, 1H, J1,2 = 8.6 Hz, H-1), Hz, J12eq,12ax= 12.6 Hz, H-12eq), 1.96 (m, 1H, H-2a), 1.93 (m, 1H, H-
6.72 (dd, 1H, J2,4= 2.8 Hz, H-2), 6.67 (d, 1H, H-4), 4.17 (t, 2H, JH,H= 5.6 25), 1.84 (m, 1H, H-20), 1.82 (m, 1H, H-1a), 1.82 (m, 1H, H-7a), 1.55
Hz, CH2O), 3.95 (t, 2H, CH2N), 2.90 (m, 2H, H-6a, H-6b), 2.50 (dd, 1H, (m, 1H, H-22a), 1.52 (m, 1H, H-8), 1.50 (m, 1H, H-2b), 1.47 (m, 2H,
J15,16a= 8.5 Hz, J16a,16b = 19.0 Hz, 1H, H-16a), 2.39 (m, 1H, H-11a), H-11), 1.46 (m, 1H, H-7b), 1.41 (m, 1H, H-23a), 1.40 (m, 1H, H-24a),
2.26 (td, 1H, J8,9=J9,11β=10.6 Hz, J9,11α=4.1 Hz, H-9), 2.14 (dt, 1H, 1.30 (m, 1H, H-24b), 1.30 (m, 1H, H-23b), 1.15 (ddd, J15eq,15ax
J15a,16b=J15b,16b=8.9 Hz, H-16b), 2.08 2.00 (m, 2H, H-15a, H-7a), J14,15ax= 13.4 Hz, J15ax,16= 4.6 Hz, 1H, H-15ax), 1.10 (m, 1H, H-12ax),
1.97 1.94 (m, 1H, H-12a), 1.68-1.42 (m, 6H, H-15b, H-8, H-14, H- 1.06 (m, 1H, H-22b), 1.05 (m, 1H, H-1b), 1.04 (d, 3H, J25,27= 6.7 Hz,
11b, H-12b, H-7b), 0.91 (s, 3H, CH3-18); 13C-NMR (125.7 MHz, CDCl3) CH3-27), 1.00 (s, 3H, CH3-19), 0.97 (m, 1H, H-17), 0.96 (d, 3H, J20,21
=
−
−
=
δ 221.3 (C-17), 155.9 (C-3), 137.8 (C-5), 133.5 (C-10), 126.8 (C-1, 6.7 Hz, CH3-21), 0.91 (m, 1H, H-9), 0.87 (s, 3H, CH3-18), 0.85 (m, 1H,
NCSe), 115.2 (C-4), 112.5 (C-2), 65.7 (CH2O), 50.5 (C-14), 48.1 (C-13), H-14). 13C-NMR (125.7 MHz, CDCl3) δ 140.9 (C-5), 121.5 (C-6), 102.5
45.2 (CH2N), 44.1 (C-9), 38.4 (C-8), 36.0 (C-16), 31.7 (C-12), 29.7 (C- (SeCN), 72.4 (C-16), 71.8 (C-3), 61.4 (C-17), 54.5 (C-14), 50.1 (C-9),
42.3 (C-4), 42.3 (C-13), 39.9 (C-12), 37.9 (C-26), 37.2 (C-1), 37.0 (C-
14 | J. Name., 2012, 00, 1-3
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