16 alpha-bromosteroid compound and its synthesis method

A technology of steroid compound and synthesis method, which is applied in the field of a class of 16α-bromo steroid compound and its synthesis, and can solve the problem of no literature report and the like

Inactive Publication Date: 2006-09-13
SHANGHAI INST OF ORGANIC CHEMISTRY - CHINESE ACAD OF SCI
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Problems solved by technology

Synthesis of steroidal drugs and steroidal molecules with potential biological activity f...
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Abstract

The invention relates to 16alpha-bromization steroid compounding and the synthetic method. When the pregnant sterol and the acetlyation bromization reagent have the reaction of the regioselective acetylation,a series of 16alpha-bromization steroid compound of the novel fabric are gained. The formula of the steroid compound is the above formula, so represents the turning up or the adown; R1 is H, OH, 0Ac, OMOM or OTBDPS; R2 is H or Br; R3 is H, Br or R3 and R4 form the 5,6-double bond; R4 is H or Br; R5 is H, OH, Oac or OMOM; thereinto, Ac is the acetyl, TBDPS is the tertiary diphenyl silicone base, MOM is the methoxy methylene. The method provided by the invention is simple, fit for the industrialized produce and makes it possible to utilize effectively the pregnant sterol (the degradation product of the steroid sapogenines).

Application Domain

Steroids preparation

Technology Topic

Double bondRegioselectivity +6

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  • 16 alpha-bromosteroid compound and its synthesis method
  • 16 alpha-bromosteroid compound and its synthesis method
  • 16 alpha-bromosteroid compound and its synthesis method

Examples

  • Experimental program(7)

Example Embodiment

[0022] Example 1 Synthesis of Compounds 2a and 2b
[0023]
[0024] Put 1 g (3 mmol) of pregnatriol 1a in a 25 ml dry reaction flask, and under stirring, control the temperature at 0° C., and add 6 ml of 30% hydrogen bromide-acetic acid solution. After pregnatriol was dissolved in 30% hydrogen bromide-acetic acid solution, the temperature was raised to 45°C and the reaction was continued for 1.5 hours. The reaction was followed by TLC and the pregnantriol reaction was complete. The acetic acid was distilled off under reduced pressure, and the obtained residue was dissolved in diethyl ether. The ether solution was washed with saturated sodium bicarbonate solution and saturated brine, dried over anhydrous sodium sulfate, and the resulting crude reaction product was concentrated and subjected to silica gel column chromatography to obtain 1.176 g of compound 2a (yield 82%) and 0.134 g of compound 2b (yield 82%). rate 9%).
[0025] Compound 2a, colorless crystal, m.p.123~125℃, [α] 20 D -13.1(c 0.95, CHCl 3 ); 1 H-NMR (CDCl 3 , 300MHz)δ: 0.64(s, 3H), 0.82(s, 3H), 1.33(d, J=5.2Hz, 3H), 2.06(s, 3H), 2.07(s, 3H), 4.29(ddd, J =7.1, 7.5, 1.3Hz, 1H), 4.69 (m, 1H), 5.09 (m, 1H); IR (liquid paraffin) v: 2924, 2845, 1732, 1433, 1384, 1245, 1033cm -1; MS (70ev) m/z (%): 424 (M + +1-AcOH, 2), 395 (424-C 2 H 5 , 2), 343 (424-Br, 12), 283 (343-AcOH, 100); elemental analysis calculated value C 25 H 39 O 4 Br: C 62.11, H 8.07; found C 62.17, H 8.17.
[0026] Compound 2b, colorless crystal, m.p.122~123℃, [α] 20 D -20.5(c 0.10, CH 2 Cl 2 ); 1 H-NMR (CDCl 3 , 300MHz)δ: 0.64(s, 3H), 0.78(s, 3H), 1.31(d, J=6.3Hz, 3H), 2.07(s, 3H), 4.29(m, 1H), 4.73(m, 1H) ), 5.09 (m, 1H); IR (liquid paraffin) v: 2917, 2843, 1723, 1458, 1384, 1278, 1033cm -1; Elemental analysis calculated value C 23 H 36 O 2 Br 2 : C 54.77, H 7.19; found C54.52, H 7.68.

Example Embodiment

[0027] Example 2 Synthesis of Compounds 2a and 2c
[0028]
[0029] Put 339 mg (1 mmol) of pregesterone 1a in a 25 ml dry reaction flask, and add 1 ml of anhydrous dichloromethane to dissolve. With stirring at room temperature, 2 ml of 30% hydrogen bromide-acetic acid solution (5 mmol) was added dropwise to the reaction flask. After dropping, the temperature was raised to 30°C and the reaction was continued for 1 hour. The reaction was followed by TLC. After the reaction of pregnantriol was completed, acetic acid and dichloromethane were distilled off under reduced pressure to obtain a residue. The obtained residue was dissolved in ether, washed with saturated sodium bicarbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated to obtain a crude reaction product. The crude reaction product was subjected to silica gel column chromatography (column chromatography eluent: petroleum ether (boiling range 60-90°C)/ethyl acetate, gradient) to obtain 372 mg of compound 2a (yield 47%) and 399 mg of colorless oily compound 2c (39% yield).
[0030] Compound 2a, data as before.
[0031] Compound 2c, [α] 20 D -12.9(c 0.72, CHCl 3 ); 1 H-NMR (CDCl 3 , 300MHz)δ: 0.64(s, 3H), 0.80(s, 3H), 1.31(d, J=6.3Hz, 3H), 2.07(s, 3H), 3.62(m, 1H), 4.29(m, 1H) ), 5.09 (dq, J=6.3, 6.7Hz, 1H); IR(KBr) v: 3468, 2924, 1706, 1377, 1274, 1243, 1053cm -1; MS (70ev) m/z (%): 365 (M + -AcOH-Me, 3), 353 (M + +2-AcOH-C 2 H 5 , 4), 351 (M + -AcOH-C 2 H 5 , 4), 301 (M + -AcOH-Br, 75), 215 (100); elemental analysis calculated value C 23 H 37 O 3 Br: C 62.58, H 8.45; found C 62.64, H 8.59.

Example Embodiment

[0032] Example 3 Synthesis of compound 2d
[0033]
[0034] Put 0.832g (2.36mmol) of pregesterol 1b in a 25ml dry reaction flask, and under stirring, control the temperature at 0°C, and add 5ml of 30% hydrogen bromide-acetic acid solution. After pregesterol was dissolved in 30% hydrogen bromide-acetic acid solution, the temperature was raised to 45°C and the reaction was continued for 2 hours. The reaction was followed by TLC, and the reaction of pregesterol was complete. The acetic acid was distilled off under reduced pressure, and the obtained residue was dissolved in diethyl ether. The ether solution was washed with saturated sodium bicarbonate solution and saturated brine, dried over anhydrous sodium sulfate, and the resulting crude reaction product was concentrated and subjected to silica gel column chromatography to obtain 1.026 g of compound 2d (yield 80.2%).
[0035] compound 2d, 1 H-NMR (CDCl 3 , 300MHz)δ: 0.65(s, 3H), 0.80(s, 3H), 1.35(d, J=5.2Hz, 3H), 2.04(s, 3H), 2.06(s, 3H), 2.07(s, 3H) ), 4.27 (ddd, J=7.1, 7.5, 1.3Hz, 1H), 4.54 (m, 1H), 4.69 (m, 1H), 5.07 (m, 1H); IR (liquid paraffin) v: 2921, 1737, 1732, 1431, 1382, 1242, 1031cm -1; MS m/z (%): 542(75), 540(73); Elemental analysis calculated value C 27 H 41 BrO 6 : C59.89, H 7.63; Found C 59.85, H 7.68.

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