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DOI: 10.1055/s-2002-34947
Stereoselective Approach to some Novel 16-Methylated and 16-Halomethylated Tetrahydropyran and δ-Lactone Derivatives in both the Normal and the 13α-Estrone Series
Publication History
Publication Date:
21 October 2002 (online)
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Abstract
Intramolecular cyclizations of the 3-methyl ether of an unsaturated d-secoestrone alcohol and secoestrone carboxylic acid in both the normal and the 13α-estrone series are reported. The ring-closure reactions furnished substituted, new oxa-d-homoestrone derivatives stereoselectively.
Key words
cyclizations - etherification - esterification - diastereoselectivity - estrone derivatives
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References
General Procedure
for the Synthesis of 16-Methyl Tetrahyropyrans: Compound 3 or 4 (300 mg,
1.00 mmol) was dissolved in CH2Cl2 (5 mL)
and BF3·OEt2 (48% solution in
Et2O, 0.47 mL, 1.5 mmol) was added drop wise during stirring
of the mixture under reflux for 72 h. The solution was then diluted
with water (10 mL) and extracted with CH2Cl2 (3 × 10
mL), and the combined organic phases were dried over Na2SO4.
Evaporation in vacuo and purification by column chromatography (silica
gel, CH2Cl2) afforded 5 (261 mg,
87%) or 9 (168 mg, 56%)
and 10 (90 mg, 30%). 5: A colorless oil; Rf = 0.43
(CH2Cl2). 1H NMR (500
MHz, CDCl3): δ = 1.15
(s, 3 H, 18-H3), 1.16 (d, 3 H, J = 6.8 Hz, 16a-H3),
2.83 (m, 2 H, 6-H2), 3.15 (d, 1 H, J = 11.3
Hz, one of 17-H2), 3.54 (m, 1 H, 16α-H), 3.76
(s, 3 H, 3-OMe), 3.81 (d, 1 H, J = 11.3 Hz, the other17-H2),
6.63 (d, 1 H, J = 2.3 Hz, 4-H), 6.70
(dd, 1 H, J = 8.6
Hz, J = 2.3
Hz, 2-H) and 7.18 (d, 1 H, J = 8.6 Hz, 1-H). 13C
NMR (125 MHz, CDCl3): δ = 22.1
(C-16a), 26.8, 27.3, 27.8 (C-18), 30.2, 30.7, 32.6 (C-13), 37.0,
37.6, 43.0, 45.0, 55.2 (3-OMe), 68.1 (C-16), 71.6 (C-17), 111.6
(C-2), 113.4 (C-4), 126.4 (C-1), 132.8 (C-10), 138.1 (C-5) and 157.6
(C-3). MS (EI): m/z (relative intensity) = 300
(M+, 100). - C20H28O2. 9: Mp 99-101 °C.
Rf = 0.47
(CH2Cl2). 1H NMR (300
MHz, CDCl3): δ = 0.98 (s,
3 H, 18-H3), 1.22 (d, 3 H, J = 6.0 Hz, 16a-H3),
2.84 (m, 2 H, 6-H2), 3.22 (d, 1 H, J = 10.6
Hz, one 17-H2), 3.46 (m, 1 H, 16α-H), 3.47 (d,
1 H, J = 10.6
Hz, the other 17-H2), 3.78 (s, 3 H, 3-OMe), 6.62 (d,
1 H, J = 2.4
Hz, 4-H), 6.72 (dd, 1 H, J = 8.6 Hz, J = 2.4
Hz, 2-H) and 7.21 (d, 1 H, J = 8.6 Hz, 1-H). 13C
NMR (125 MHz, CDCl3): δ = 16.7 (C-18), 22.1 (C-16a),
25.6 (C-11), 25.7 (C-7), 30.0 (C-6), 32.3, 34.0 (C-13), 35.4, 38.6
(C-8), 43.8 (C-9), 47.7 (C-14), 55.2 (3-OMe), 74.9 (C-16), 80.0
(C-17), 111.6 (C-2), 113.6 (C-4), 126.1 (C-1), 132.8 (C-10), 137.9
(C-5), 157.5 (C-3). IR (KBr): 1080, 1238, 1502, 1606, 2864, 2922,
2940 cm-1. MS (EI): m/z (relative
intensity) = 300 (M+, 100), 173(27). - C20H28O2. 10: A colorless oil. Rf = 0.42
(CH2Cl2). 1H NMR (300
MHz, CDCl3): δ = 1.02
(s, 3 H, 18-H3), 1.29 (d, 3 H, J = 6.9 Hz, 16a-H3),
2.84 (m, 2 H, 6-H2), 3.15 (d, 1 H, J = 11.0
Hz) and 3.40 (d, 1 H, J = 11.0
Hz, 17-H2), 3.78 (s, 3 H, 3-OMe), 4.30 (m, 1 H, 16β-H),
6.63 (d, 1 H, J = 2.5
Hz, 4-H), 6.72 (dd, 1 H, J = 8.6 Hz, J = 2.5
Hz, 2-H) and 7.21 (d, 1 H, J = 8.6 Hz, 1-H). 13C
NMR (125 MHz, CDCl3): δ = 16.2 and 17.3
(C-16a
and C-18), 25.6 (C-11), 25.8 (C-7), 28.6, 30.0, 34.5 (C-13), 35.8,
38.6 (C-8), 41.5 (C-9), 43.8 (C-14), 55.2 (3-OMe), 69.3 (C-16),
72.2 (C-17), 111.6 (C-2), 113.6 (C-4), 126.1 (C-1), 132.9 (C-10),
137.9 (C-5), 157.6 (C-3).
- C20H28O2.
The compounds give correct elemental analyses.