CN1821261A - Steroid C,D cycle rearrangement formed compounds - Google Patents

Steroid C,D cycle rearrangement formed compounds Download PDF

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CN1821261A
CN1821261A CN 200610025049 CN200610025049A CN1821261A CN 1821261 A CN1821261 A CN 1821261A CN 200610025049 CN200610025049 CN 200610025049 CN 200610025049 A CN200610025049 A CN 200610025049A CN 1821261 A CN1821261 A CN 1821261A
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compound
steroidal
compounds
omom
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田伟生
许启海
兰泉
肖晴
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Shanghai Institute of Organic Chemistry of CAS
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Shanghai Institute of Organic Chemistry of CAS
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Abstract

The present invention relates to a kind of compounds with novel structure and their synthesis process. These compounds are prepared through the [4+2] cycloaddition reaction of compound with conjugated double bond in the steroid D cycle and singlet oxygen to produce unstable beta-peroxide, and breaking and re-arrangement of the peroxide bond to obtain the compounds. The compounds have the structural expression as shown. The present invention has simple operation process, and the compounds possess carbon skeleton similar to that of tricyclene compound and may be synthesized through photocatalytic re-arrangement reaction.

Description

Steroidal C, the D ring is reset a compounds that generates
Technical field
The compound that the present invention relates to a class formation novelty with and synthetic method.[4+2] cycloaddition reaction takes place in compound and singlet oxygen that steroidal D ring has conjugated double bond, the β of generation-peralcohol instability, and the compound that obtains a class formation novelty is reset in the peroxide bridge fracture.
Technical background
The tricyclene compounds is the important compound of a class, and they extensively are present in occurring in nature, also has many analogues to be synthesized out, this compounds is many all have good biological activity (referring to J.Am.Chem.Soc.1966,88,5937; Aust.J.Chem.1990,43; 21; Eur.J.Org.Chem.2004,17,3686; J.Nat.Prod.2001,64,389; J.Nat.Prod.2001,64,1489):
Figure A20061002504900041
[4+2] cycloaddition reaction can take place with singlet oxygen in the compound that steroidal D ring has conjugated double bond, generate α-peralcohol, α-peralcohol reduction fracture peroxide bridge can obtain 14, and the 17-dihydroxyl compound is (referring to J.Org.Chem.2002,67,4742-4746; Org.Lett.2003,5,2849-2852).People such as Tian Weisheng have conjugated double bond by the D ring and have the 22-hydroxyl or [4+2] reaction of the steroidal compounds of 22-carbonyl and singlet oxygen, obtain 14 α of a series of novel structures, and 17 α-oxo bridge steroidal compounds pass through zinc powder reduction and S again NA series of conversions such as 2 ' replacement obtain a series of 17 Alpha-hydroxy steroidal lactones and 17 Alpha-hydroxy steroidal inner ethers smoothly, realized 17 alpha-hydroxy introducings and steroidal E the ring structure (CN 200610024586.0; CN 200610024780.9).17 Alpha-hydroxy steroidal lactones and 17 Alpha-hydroxy steroidal inner ethers all are important synthetic precursors, can be used for synthesizing Cephalostatine molecule such as Cephalostatin 1 (CN 200310108533.3) and other and contain 17 alpha-hydroxy steroidal compounds.
In [4+2] of above-mentioned singlet oxygen cycloaddition process, except generating α-peralcohol, also generate β-peralcohol simultaneously, β-peroxide bridge and 18-angular methyl(group) are in the same one side of steroidal D ring, because the influence of 18-angular methyl(group), the D ring of β-superoxide is too crowded, causes the peroxide bridge homolysis, then C 8-C 14, C 13-C 17The compound 3 that can obtain a class formation novelty is reset in bond rupture:
Figure A20061002504900051
From the coupling constant of hydrogen spectrum as can be seen, in the compound 3 after the rearrangement 15, the two keys of 16-still keep Z formula configuration, and the X diffractogram of compound 3e monocrystalline has further been proved conclusively the structure of this compounds.
The method of compound 3 reference literatures and simple substance bromine addition (referring to Can.J.Chem.1957,35,236; Chem.Ber.1972,105,929), can obtain the product 4 of two bromos:
Compound 3 is closely similar with the carbon skeleton of tricyclene compounds noted earlier, and the photochemical rearrangement reaction can be used as the New Policy of synthetic this compounds.
Summary of the invention
The compound that the purpose of this invention is to provide a class formation novelty.
Another object of the present invention provides the method for synthetic above-claimed cpd.
14 α of the present invention, the structure of 17 α-oxo bridge steroidal compounds is as follows:
Figure A20061002504900062
Represent singly-bound or two key; R 1Be H, MOM, Bn, THP, Ac, Bz, Piv, TMS, TES, TBS or TBDPS; R 2Be H, OH, OAc, OBz, OPiv, OTES, OTBS or OTBDPS; R 3Be H, OH, OMOM, OBn, OTHP, OAc, OBz, OPiv, OTMS, OTES, OTBS or OTBDPS; R 4For H, Me, Et, Pr, Perhaps with R 5Become carbonyl; R 5Be H, Me, Et, Pr or and R 4Become carbonyl; R 6Be H, OH, OMOM, OBn, OTHP, OAc, OBz, OPiv, OTMS, OTES, OTBS, OTBDPS or R 6With R 7Acetone becomes to contract; R 7Be H, OH, OMOM or OAc; R 8Be H or Me; R 9Be H, OH, OMOM, OTES or R 9With R 10Become carbonyl or X (CH 2) nX, X are oxygen or sulphur, n=2 or 3; R 10Be H, OH, OMOM or OTES;
Wherein, Me is a methyl, and Et is an ethyl; Pr is a propyl group, and MOM is the methoxy methylene radical, and Bn is a benzyl; THP is a THP trtrahydropyranyl; Ac is an ethanoyl, and Bz is a benzoyl, and Piv is a pivaloyl group; TMS is trimethyl silicon based; TES is that triethyl is silica-based, and TBS is that tertiary butyl dimethyl is silica-based, and TBDPS is that tert-butyl diphenyl is silica-based.
The synthetic method of compound of the present invention is as follows:
In organic solvent and in the presence of the photosensitizers, conjugated diene compound 1 stirs under-10 ℃～100 ℃ and illumination and feeds excess of oxygen 0.1～24h, obtain compound 3 and α-peralcohol 2, compound 1 is 1: 0.001～0.5 with the mol ratio of photosensitizers, the used light source of illumination is the tungsten incandescent light of natural light or 5～1000 watts, and described photosensitizers is tetraphenylporphyrin (TPP), methylene blue (MB), rose-red (RB) or acridine orange (RO).
Organic solvent described in the above-mentioned reaction is methylene dichloride, trichloromethane, tetracol phenixin, ethylene dichloride, ether, the tetrahydrochysene furan food in one's mouth (THF), 1,4-diox (dioxane), benzene, toluene or acetonitrile, the structural formula of described compound 1, compound 2 and compound 3 is as follows:
Wherein R 1～R 5Described as defined above.
The carbon skeleton of compound of the present invention and aforementioned tricyclene compounds is closely similar, and the photochemical rearrangement reaction can be used as the New Policy of synthetic this compounds.
Description of drawings
Fig. 1 is the X diffractogram of compound 3e monocrystalline of the present invention.
Specific implementation method
To help to understand the present invention by following specific implementation method, but not limit content of the present invention.
Raw material 1a～1h that the present invention uses can obtain by patented method (CN 200610024586.0) is synthetic.
Embodiment 1 compound 3a's is synthetic
Figure A20061002504900072
0.574g 1a is dissolved in the anhydrous CH of 30mL 2Cl 2In, adding 6mg TPP (0.5%eq), ice bath feeds excess of oxygen, illumination.TLC follows the tracks of and detects to the reaction end.Concentrate, column chromatography gets 245mg compound 2a, yield 40%, 292mg compound 3a, yield 47%.
Compound 2a white plates crystal C 28H 44O 8FW 508 m.p.96-97 ℃
[α] D 19＝52.3°(c＝0.90，CHCl 3)
1HNMR(CDCl 3)：δ6.44(1H，d，J＝19.2Hz，16-H)，6.42(1H，d，J＝19.2Hz，15-H)，4.70(2H，m，12-OCH 2OCH 3)，4.68(2H，s，3-OCH 2OCH 3)，4.23-4.20(2H，m，22-H)，4.20(1H，dd，J 1＝11.7Hz，J 2＝4.5Hz，12-H)，3.51(1H，m，3-H)，3.37(3H，s，12-OCH 2OCH 3)，3.36(3H，s，3-OCH 2OCH 3)，2.53(1H，q，J＝6.0Hz，20-H)，2.07(3H，s，22-OAc)，1.14(3H，d，J＝6.3Hz，21-CH 3)，0.97(3H，s，18-CH 3)，0.83(3H，s，19-CH 3)
IR(KBr)υ(cm -1)：3059，2941，2866，1743，1231，1039，917
EIMS(m/z)：508(M +)
Ultimate analysis: calculated value (%) C66.12 H8.72
Measured value (%) C66.15 H8.72
Compound 3a light yellow oil C 28H 44O 8FW 508
[α] D 17.9＝-44.4°(c＝0.82，CHCl 3)
1HNMR(CDCl 3)：δ6.42(1H，d，J＝20.7Hz，16-H)，6.39(1H，d，J＝19.2Hz，15-H)，4.67(2H，s，3-OCH 2OCH 3)，4.66(1H，AB，J＝6.6Hz，12-OCH 2OCH 3)，4.61(1H，AB，J＝6.6Hz，12-OCH 2OCH 3)，4.52(1H，dd，t?like，J＝6.9Hz，12-H)，4.21(2H，m，22-H)，3.49(1H，m，3-H)，3.36(3H，s，12-OCH 2OCH 3)，3.35(3H，s，3-OCH 2OCH 3)，2.99(1H，q，J＝6.6Hz，20-H)，2.06(3H，s，22-OAc)，1.24(3H，s，18-CH 3)，1.13(3H，d，J＝6.0Hz，21-CH 3)，0.78(3H，s，19-CH 3)
13CNMR(CDCl 3)：δ206.5，203.5，170.6，135.8，96.1，94.3，80.0，76.0，64.9，57.8，55.2，54.9，51.0，50.2，44.7，43.9，37.3，35.0，34.2，32.4，28.9，28.0，27.4，20.6，17.7，12.8，11.0
IR(KBr)υ(cm -1)：2937，2860，1745，1699，1606，1451，1374，1234，1044
EIMS(m/z)：508(M +)
Ultimate analysis: calculated value (%) C66.12 H8.72
Measured value (%) C66.04 H8.78
Embodiment 2 compound 3b's is synthetic
Figure A20061002504900081
0.637g compound 1b is dissolved in the anhydrous CH of 30mL 2Cl 2In, adding 6mg TPP (0.5%eq), ice bath feeds excess of oxygen, illumination.TLC follows the tracks of and detects to the reaction end.Concentrate, column chromatography gets 210mg compound 2b, yield 31%, 422mg compound 3b, yield 62%.
Compound 2b white solid C 26H 42O 7FW 466 m.p.110-111 ℃
[α] D 17.1＝35.4°(c＝1.165，CHCl 3)
1HNMR(CDCl 3)：δ6.47(2H，s，15-H，16-H)，4.73(2H，AB，J＝6.6Hz，12-OCH 2OCH 3)，4.67(2H，s，3-OCH 2OCH 3)，4.06(1H，dd，J 1＝11.4Hz，J 2＝4.2Hz，12-H)，3.68(2H，m，22-H)，3.50(1H，m，3-H)，3.37(3H，s，12-OCH 2OCH 3)，3.33(3H，s，3-OCH 2OCH 3)，2.67(1H，q，J＝6.0Hz，20-H)，1.14(3H，d，J＝6.3Hz，21-CH 3)，0.97(3H，s，18-CH 3)，0.83(3H，s，19-CH 3)
13CNMR(CDCl 3)：δ134.4，133.9，98.6，98.3，98.3，96.1，94.5，76.6，75.9，75.5，64.0，63.9，55.9，55.1，45.6，44.0，36.7，35.6，34.9，33.1，28.5，28.4，27.2，26.4，14.7，13.0，11.5
IR(KBr)υ(cm -1)：3475，3065，2935，2862，2821，1471，1147，1045，914，745
Ultimate analysis: calculated value (%) C66.93 H9.07
Measured value (%) C66.95 H9.35
Compound 3b light yellow oil C 26H 42O 7FW 466
[α] D 17.1＝-29.9°(c＝0.34，CHCl 3)
1HNMR(CDCl 3)：δ6.41(2H，s，15-H，16-H)，4.65(2H，s，3-OCH 2OCH 3)，4.64(1H，AB，J＝6.6Hz，12-OCH 2OCH 3)，4.58(1H，AB，J＝6.6Hz，12-OCH 2OCH 3)，4.48(1H，dd，t?like，J＝6.9Hz，12-H)，3.76(2H，m，22-H)，3.47(1H，m，3-H)，3.33(3H，s，12-OCH 2OCH 3)，3.32(3H，s，3-OCH 2OCH 3)，2.85(1H，q，J＝7.2Hz，20-H)，1.27(3H，s，18-Me)，1.13(3H，d，J＝6.0Hz，21-CH 3)，0.76(3H，s，19-CH 3)
13CNMR(CDCl 3)：δ207.9，206.1，136.5，136.0，96.1，94.5，80.0，76.2，64.2，58.1，55.3，55.0，51.2，48.0，44.1，37.5，35.2，34.3，32.6，29.0，28.2，27.5，17.9，12.6，11.1
IR(KBr)υ(cm -1)：3471，2933，2861，1757，1695，1606，1451，1384，1148，1045，917，734
EIMS(m/z)：466(M +)
HRMS (EI), C 26H 42O 7Na + 1: calculated value 489.2820
Measured value 489.2822
Embodiment 3 compound 3c's is synthetic
Figure A20061002504900091
0.716g compound 1c is dissolved in the anhydrous CH of 30mL 2Cl 2In, adding 6mg TPP (0.5%eq), ice bath feeds excess of oxygen, illumination.TLC follows the tracks of and detects to the reaction end.Concentrate, column chromatography gets 311mg compound 2c, yield 40.8%, 157mg compound 3c, yield 20.6%.
Compound 2c C 30H 50O 7FW 522
1HNMR(CDCl 3)：δ6.15(1H，16-H，s)，5.87(1H，15-H，s)，4.71-4.61(4H，3-OCH 2OCH 3，12-OCH 2OCH 3，m)，3.55-3.48(2H，3-H，22-H，m)，3.39(3H，12-OCH 2OCH 3，s)，3.37(3H，3-OCH 2OCH 3，s)，2.67(1H，q，J＝6.0Hz，20-H)，2.85(1H，12-H，d-d，J 1＝11.1Hz，J 2＝4.5Hz)，1.06(6H，22-CH 2CH 2CH 3CH 3，s)，0.92(3H，18-H，s)，0.91(3H，21-H，d，J＝3.9Hz)，0.85(3H，19-H，s)
IR(KBr)υ(cm -1)：3475，3065，2935，2862，2821，1471，1147，1045，914，745
Ultimate analysis: calculated value (%) C68.93 H9.64
Measured value (%) C68.91 H9.55
Compound 3c light yellow oil C 30H 50O 7FW 522
1HNMR(CDCl 3)：δ6.21(1H，16-H，s)，6.08(1H，15-H，s)，4.70-4.61(4H，3-OCH 2OCH 3，12-OCH 2OCH 3，m)，3.65-3.46(2H，3-H，22-H，m)，3.39(3H，12-OCH 2OCH 3，s)，3.37(3H，3-OCH 2OCH 3，s)，2.75(1H，q，J＝6.0Hz，20-H)，2.89(1H，12-H，d-d，J 1＝11.1Hz，J 2＝4.5Hz)，1.06(6H，22-CH 2CH 2CH 2CH 3，s)，0.92(3H，18-H，s)，0.91(3H，21-H，d，J＝3.9Hz)，0.85(3H，19-H，s)
IR(KBr)υ(cm -1)：3471，3065，2933，2861，1758，1693，1606，1384，1148，1045，917，734EIMS(m/z)：522(M +)
Embodiment 4 compound 3d's is synthetic
0.883g compound 1d is dissolved in the anhydrous CH of 30mL 2Cl 2In, adding 6mg TPP (0.5%eq), ice bath feeds excess of oxygen, illumination.TLC follows the tracks of and detects to the reaction end.Concentrate, column chromatography gets 371mg compound 2d, yield 39.9%, 485mg compound 3d, yield 52.2%.
Compound 2d C 39H 60O 5Si FW 636
1HNMR(CDCl 3)：δ7.39-7.25(5H，Ar，m)，6.18(1H，16-H，s)，5.85(1H，15-H，s)，5.25(1H，6-H，d，J＝4.8Hz)，3.57(2H，26-H，t，J＝6.6Hz)，3.46(1H，3-H，m)，3.10(1H，22-H，J＝5.7Hz)，2.82(6H，23-H，24-H，25-H，m)，2.74(1H，20-H，m)，1.05(3H，21-H，d，J＝6.6Hz)，1.00(3H，18-H，s)，0.91(1H，19-H，s)，0.84(9H，-SiCMe 3，s)，0.00(6H，-SiMe 2，s)
IR(KBr)υ(cm -1)：3479，2935，2862，1470，1145，1041，913，744
Ultimate analysis: calculated value (%) C73.54 H9.49
Measured value (%) C73.39 H9.55
Compound 3d C 39H 60O 5Si FW 636
1HNMR(CDCl 3)：δ7.39-7.25(5H，Ar，m)，6.37(1H，16-H，s)，6.12(1H，15-H，s)，5.24(1H，6-H，d，J＝4.5Hz)，3.55(2H，26-H，t，J＝6.6Hz)，3.44(1H，3-H，m)，3.18(1H，22-H，J＝5.7Hz)，2.82(6H，23-H，24-H，25-H，m)，2.91(1H，20-H，m)，1.16(3H，21-H，d，J＝6.6Hz)，1.00(3H，18-H，s)，0.91(1H，19-H，s)，0.84(9H，-SiCMe 3，s)，0.00(6H，-SiMe 2，s)
IR(KBr)υ(cm -1)：3471，2934，2865，1757，1693，1606，1384，1148，1045，917，734
EIMS(m/z)：636(M +)
Embodiment 5 compound 3e's is synthetic
Figure A20061002504900111
68mg compound 1e is dissolved in the anhydrous CH of 10mL 2Cl 2In, adding 0.3mg TPP (0.5%eq), ice bath feeds excess of oxygen, illumination.TLC follows the tracks of and detects to the reaction end.Concentrate, column chromatography gets 5mg compound 2e, yield 7%, 30mg compound 3e, yield 42%.
Compound 2e white foam shape thing C 37H 60O 9S 2FW 712
[α] D 19.6＝35.7°(c＝0.66，CHCl 3)
1HNMR(CDCl 3)：δ6.63(1H，d，J＝6.0Hz，16-H)，6.31(1H，d，J＝5.7Hz，15-H)，4.77(2H，s，12-OCH 2OCH 3)，4.67(2H，s，3-OCH 2OCH 3)，4.38(1H，s，22-H)，4.18(1H，d，J＝4.2Hz，22-OH)，4.11(1H，dd，J 1＝11.4Hz，J 2＝4.2Hz，12-H)，3.88(1H，AB，J 1＝8.1Hz，26-H)，3.83(1H，AB，J 1＝8.1Hz，26-H)，3.50(1H，m，3-H)，3.37(3H，s，12-OCH 2OCH 3)，3.35(3H，s，3-OCH 2OCH 3)，3.06-2.65(6H，m，S-ketal)，1.08(3H，s，18-CH 3)，0.80(3H，s，19-CH 3)
IR(KBr)υ(cm -1)：3464，2982，2931，2863，1466，1374，1105，1043，914
ESIMS(m/z)：735.4(M ++Na)
Ultimate analysis: calculated value (%) C62.33 H8.48
Measured value (%) C62.22 H8.61
Compound 3e white foam shape thing C 37H 60O 9S 2FW 712
1HNMR(CDCl 3)：δ6.35(1H，d，J＝11.7Hz，16-H)，6.22(1H，d，J＝11.7Hz，15-H)，4.86(1H，d，J＝6.6Hz，22-H)，4.66(2H，s，3-OCH 2OCH 3)，4.65(1H，AB，J＝6.6Hz，12-OCH 2OCH 3)，4.61(1H，AB，J＝6.6Hz，12-OCH 2OCH 3)，4.40(1H，d，J＝11.1Hz，12-H)，3.91(1H，AB，J 1＝8.4Hz，26-H)，3.86(1H，AB，J 1＝9.0Hz，26-H)，3.43(1H，m，3-H)，3.40(3H，s，12-OCH 2OCH 3)，3.35(3H，s，3-OCH 2OCH 3)，2.81(1H，s，22-OH)，1.08(3H，s，18-CH 3)，0.78(3H，s，19-CH 3)
The X diffractogram of compound 3e monocrystalline as shown in Figure 1.
Embodiment 6 compound 3g's is synthetic
70mg compound 1g is dissolved in the 10mL methylene dichloride, adds photosensitizers TPP, feeds excess of oxygen, illumination.TLC tracks to reaction to be finished.Concentrate, column chromatography gets 34mg compound 2g, yield 48.5%, 36mg compound 3g, yield 51.4%.
Compound 2g white foam shape thing C 35H 52O 10FW 632
[α] D 18＝13.3°(c＝0.73，CHCl 3)
1HNMR(CDCl 3)：δ6.41(d，J＝5.7Hz，1H，16-H)，6.35(d，J＝5.7Hz，1H，15-H)，5.33(dd，J 1＝11.4Hz，J 2＝4.8Hz，1H，12-H)，5.09(t，J＝6.3Hz，1-H，22-H)，4.68(m，1H，3-H)，3.87(m，1H，26-H)，2.05-2.02(s，12H，3-，12-，22-，26-OCOCH 3)，1.12(d，3H，J＝6.9Hz，21-Me)，1.01(s，3H，18-Me)，0.92(d，J＝6.9Hz，3H，27-Me)0.82(s，3H，19-Me)
IR(KBr)υ(cm -1)：2929，2866，1737，1718，1581，1466，1373，1238，1045，1023，978，755
EIMS(m/z)：572(M +-CH 3COOH)
HRMS (EI), C 35H 52O 10Na + 1: calculated value 655.3458
Measured value 655.3453
Compound 3g light yellow oil C 35H 52O 10FW 632
[α] D 18.8＝-33.1°(c＝1.60，CHCl 3)
1HNMR(CDCl 3)：δ6.51(d，J＝12.3Hz，1H，16-H)，6.46(d，J＝12.3Hz，1H，15-H)，5.33(t，J＝7.2Hz，1H，12-H)，5.16(m，1H，22-H)，4.66(m，1H，3-H)，3.88(m，1H，26-H)，3.03(m，1H，20-H)，2.05-2.02(s，12H，3-，12-，22-，26-OCOCH 3)，0.93(d，J＝6.9Hz，3H，27-Me)，0.78(s，3H，19-Me)
IR(KBr)υ(cm -1)：2928，2858，1737，1702，1601，1459，1373，1243，1022，983，607
EIMS(m/z)：632(M +)
HRMS (EI), C 35H 52O 10Na + 1: calculated value 655.3458
Measured value 655.3453
Embodiment 7 compound 3h's is synthetic
Substrate 1h 0.091g (0.18mmol) is dissolved in 10mL exsiccant methylene dichloride, and ice bath adds a little TPP down, feeds excessive oxygen, and 100W incandescent light photograph heats up naturally, and 2h reacts end.Pressure reducing and steaming solvent, silica gel column chromatography get yellow oily compound 2h 0.025g, yield 25.9%, yellow oily compound 3h 0.049g, yield 50.7%.
The faint yellow oily thing of compound 2h C 31H 50O 8550
[α] D 20.7＝+38.21°(c＝0.71，CHCl 3)
1H?NMR(CDCl 3)：δ6.50(d，1H，J＝6Hz，15-H?or?16-H)，6.40(d，1H，J＝5.7Hz，15-Hor?16-H)，4.71(s，2H，12-OCH 2OCH 3)，4.69(s，2H，3-OCH 2OCH 3)，4.22(s，1H，22-Ha)，4.20(s，1H，22-Hb)，4.04(dd，1H，J 1＝12.0Hz，J 2＝4.5Hz，12-H)，3.51(m，1H，3-H)，3.38(s，3H，12-OCH 2OCH 3)，3.36(s，3H，3-OCH 2OCH 3)，2.54(m，1H，20-H)，1.23(s，9H，16-OC(CH 3) 3)，1.18(d，3H，J＝7.2Hz，21-CH 3)，0.97(s，3H，18-CH 3)，0.82(s，3H，19-CH 3)
13C?NMR(CDCl 3)：δ178.32，134.65，133.19，98.26，98.19，96.38，94.54，75.93，75.49，65.77，64.09，55.71，55.11，45.63，44.02，38.80，36.77，35.65，34.98，33.17，31.69，28.60，28.46，27.16，27.08，26.81，14.34，13.02，11.55
IR(KBr)ν(cm -1)：2932，2832，1731，1481，1284，1150，1105，1044，916，547
ESI-Ms(m/z)：551.5[M+H +]；568.3[M+NH 4 +]；573.4[M+Na +]；589.3[M+K +]
HRMS (ESI), [C 31H 50O 8Na] +: calculated value 573.3397
Measured value 573.3398
The faint yellow oily thing of compound 3h C 31H 50O 8FW 550
[α] D 20.5＝-31.19°(c＝0.7367，CHCl 3)
1H?NMR(300MHz，CDCl 3)：δ6.43(d，1H，J＝9Hz，15-H?or?16-H)，6.38(d，1H，J＝12Hz，15-H?or?16-H)，4.63(m，4H，12-OCH 2OCH 3，3-OCH 2OCH 3)，4.19(m，2H，22-Ha，22-Hb)，3.49(m，1H，3-H)，3.363(s，3H，12-OCH 2OCH 3)，3.355(s，3H，3-OCH 2OCH 3)，2.99(dd，1H，J 1＝13.2Hz，J 2＝6.3Hz，12-H)，1.23(d，3H，J＝7.8Hz，21-CH 3)，1.20(s，3H，18-CH 3)，1.19(s，9H，16-OC(CH 3) 3)，0.78(s，3H，19-CH 3)；
ESI-MS(m/z)：551.3[M+H +]；573.4[M+Na +]；589.3[M+K +]；
Embodiment 8 compound 3j's is synthetic
Figure A20061002504900141
0.291g (0.67mmol) compound 1j is dissolved in 12mL exsiccant methylene dichloride, ice-water bath adds 2mg TPP down, feeds excess of oxygen, and 100W incandescent light photograph heats up naturally, and TLC shows that the 2h afterreaction finishes.Pressure reducing and steaming solvent, silica gel column chromatography get white solid 2j 0.094g, yield 30.1%, compound 3j 0.049g, yield 15.7%.
Compound 2j off-white color solid C 26H 40O 7464 m.p.:100～101 ℃
[α] D 20＝+70°(c＝0.145，CH 2Cl 2)
1H?NMR(300MHz，CDCl 3)：δ9.88(d，1H，J＝1.8Hz，22-CHO)，6.44(s，2H，15-Hand?16-H)，4.72，4.71(AB，2H，J AB＝6.9Hz，12-OCH 2OCH 3)，4.68(s，2H，3-OCH 2OCH 3)，4.08(dd，1H，J 1＝12Hz，J 2＝4.8Hz，12-H)，3.50(m，1H，3-H)，3.37(s，3H，12-OCH 2OCH 3)，3.367(s，3H，3-OCH 2OCH 3)，3.25(m，1H，20-H)，1.25(d，3H，J＝6.9Hz，21-CH 3)，0.94(s，3H，18-CH 3)，0.83(s，3H，19-CH 3)
13C?NMR(75MHz，CDCl 3)：200.72，134.11，133.95，98.37，96.32，94.52，75.87，75.41，64.45，55.77，55.12，45.64，44.68，44.05，36.76，35.65，34.93，33.24，28.52，28.43，27.28，26.67，13.07，11.54，10.77
IR(KBr)υ(cm -1)：2979，2927，1718，1456，1442，1148，1102，1043，915，743，709
ESI-Ms(m/z)：482.4[M+NH 4 +]
HRMS (ESI), C 26H 40O 7Na + 1: calculated value 487.2672
Measured value 487.2666
Compound 3j yellow oil C 26H 40O 7464
1H?NMR(300MHz，CDCl 3)：δ9.86(d，1H，J＝1.8Hz，22-CHO)，6.58(s，2H，15-Hand?16-H)，4.72，4.71(AB，2H，J AB＝6.9Hz，12-OCH 2OCH 3)，4.68(s，2H，3-OCH 2OCH 3)，4.15(dd，1H，J 1＝12Hz，J 2＝4.8Hz，12-H)，3.50(m，1H，3-H)，3.37(s，3H，12-OCH 2OCH 3)，3.37(s，3H，3-OCH 2OCH 3)，3.34(m，1H，20-H)，1.45(d，3H，J＝6.9Hz，21-CH 3)，0.94(s，3H，18-CH 3)，0.83(s，3H，19-CH 3)
IR(KBr)υ(cm -1)：2927，1757，1718，1695，1456，1148，1102，1043，916，745，708
ESI-Ms(m/z)：482.4[M+NH 4 +]
Embodiment 9 compound 3k's is synthetic
Figure A20061002504900151
0.302g (0.67mmol) compound 1k is dissolved in 12mL exsiccant methylene dichloride, ice-water bath adds 2mgTPP down, feeds excess of oxygen, and 100W incandescent light photograph heats up naturally, and TLC shows that the 4h afterreaction finishes.Pressure reducing and steaming solvent, silica gel column chromatography get white solid 2k 0.125g, yield 38.6%, compound 3k 0.039g, yield 12.0%.
Compound 2k white solid C 24H 40O 8480 m.p.143～144 ℃ (acetone)
[α] D 20＝+33.57°(c＝0.176，CHCl 3)
1H?NMR(300MHz，CDCl 3)：δ6.66(d，1H，J＝6Hz，15-H?or?16-H)，6.40(d，1H，J＝6Hz，15-H?or?16-H)，4.77(s，2H，12-OCH 2OCH 3)，4.69(s，2H，3-OCH 2OCH 3)，4.09(q，1H，J＝4.8Hz，20-H)，3.53(m，1H，3-H)，3.43(s，3H，12-OCH 2OCH 3)，3.38(s，3H，3-OCH 2OCH 3)，3.17(dd，1H，J 1＝10.2Hz，J 2＝6.9Hz，12-H)，1.40(d，3H，J＝6.6Hz，21-CH 3)，0.92(s，3H，18-CH 3)，0.83(s，3H，19-CH 3)
13C?NMR(75MHz，CDCl 3)：177.04，134.36，132.72，98.41，96.29，96.20，94.44，75.96，75.39，64.56，55.90，45.61，43.99，37.65，36.72，35.63，34.89，33.39，28.49，28.39，27.21，26.64，14.93，12.09，11.52
IR(KBr)υ(cm -1)：3438，3060，2942，2830，1740，1464，1184，1105，927
ESI-Ms(m/z)：479.2[M-H +]
HRMS (ESI), C 26H 40O 8Na + 1: calculated value 503.2621
Measured value 503.2615
Compound 3k yellow oil C 24H 40O 8480
1H?NMR(300MHz，CDCl 3)：δ6.60(s，2H，15-H?and?16-H)，4.79(s，2H，12-OCH 2OCH 3)，4.70(s，2H，3-OCH 2OCH 3)，4.49(m，1H，20-H)，3.53(m，1H，3-H)，3.48(s，3H，12-OCH 2OCH 3)，3.37(s，3H，3-OCH 2OCH 3)，3.21(dd，1H，J 1＝10.2Hz，J 2＝6.9Hz，12-H)，1.52(d，3H，J＝6.6Hz，21-CH 3)，0.92(s，3H，18-CH 3)，0.83(s，3H，19-CH 3)
IR(KBr)υ(cm -1)：3439，3061，2942，1759，1742，1697，1464，1184，1105，927
Embodiment 10 compound 4a's is synthetic
Figure A20061002504900171
0.127g 3a is dissolved in 5mLCHCl 3In, 0 ℃ of Br that drips 1.1eq. 2, room temperature reaction 3h, raw material disappears.Saturated NaHSO 3Saturated NaHCO is used in cancellation, organic phase respectively 3With saturated common salt water washing, MgSO 4Drying is filtered, and is spin-dried for, and column chromatography gets 0.149g compound 4a, yield 89.2%.
Compound 4a light yellow oil C 28H 44Br 2O 8FW 668
1HNMR(CDCl 3)：δ4.98(1H，s，16-H)，4.95(1H，s，15-H)，4.66(2H，s，3-OCH 2OCH 3)，4.64(1H，AB，J＝6.3Hz，12-OCH 2OCH 3)，4.61(1H，AB，J＝6.3Hz，12-OCH 2OCH 3)，4.55(1H，dd，t?like，J＝6.9Hz，12-H)，4.20(2H，m，22-H)，3.49(1H，m，3-H)，3.35(3H，s，12-OCH 2OCH 3)，3.34(3H，s，3-OCH 2OCH 3)，3.02(1H，q，J＝6.6Hz，20-H)，2.06(3H，s，22-OAc)，1.28(3H，s，18-CH 3)，1.17(3H，d，J＝6.0Hz，21-CH 3)，0.78(3H，s，19-CH 3)
IR(KBr)υ(cm -1)：2935，1747，1703，1605
Ultimate analysis: calculated value (%) C50.31 H6.63
Measured value (%) C50.34 H6.68.

Claims (4)

1, a class steroidal C, the D ring is reset the compound that generates, and it is characterized in that having following structure:
Figure A2006100250490002C1
Represent singly-bound or two key; R 1Be H, MOM, Bn, THP, Ac, Bz, Piv, TMS, TES, TBS or TBDPS; R 2Be H, OH, OAc, OBz, OPiv, OTES, OTBS or OTBDPS; R 3Be H, OH, OMOM, OBn, OTHP, OAc, OBz, OPiv, OTMS, OTES, OTBS or OTBDPS; R 4For H, Me, Et, Pr,
Figure A2006100250490002C3
Perhaps with R 5Become carbonyl; R 5Be H, Me, Et, Pr or and R 4Become carbonyl; R 6Be H, OH, OMOM, OBn, OTHP, OAc, OBz, OPiv, OTMS, OTES, OTBS, OTBDPS or R 6With R 7Acetone becomes to contract; R 7Be H, OH, OMOM or OAc; R 8Be H or Me; R 9Be H, OH, OMOM, OTES or R 9With R 10Become carbonyl or X (CH 2) nX, X are oxygen or sulphur, n=2 or 3; R 10Be H, OH, OMOM or OTES;
Wherein, Me is a methyl, and Et is an ethyl; Pr is a propyl group, and MOM is the methoxy methylene radical, and Bn is a benzyl; THP is a THP trtrahydropyranyl; Ac is an ethanoyl, and Bz is a benzoyl, and Piv is a pivaloyl group; TMS is trimethyl silicon based; TES is that triethyl is silica-based, and TBS is that tertiary butyl dimethyl is silica-based, and TBDPS is that tert-butyl diphenyl is silica-based.
2, a kind of synthetic method of steroidal compounds as claimed in claim 1 is characterized in that by following method synthetic:
In organic solvent and in the presence of the photosensitizers, the steroidal conjugated dienes stirs under-10 ℃～100 ℃ and illumination and feeds excess of oxygen 0.1～24h, obtain compound as claimed in claim 1, the mol ratio of steroidal conjugated dienes and photosensitizers is 1: 0.001～0.5, and described photosensitizers is tetraphenylporphyrin, methylene blue, rose-red or acridine orange;
The structural formula of described steroidal conjugated dienes is as follows:
Figure A2006100250490002C4
Wherein R 1～R 5Definition according to claim 1.
3, the synthetic method of steroidal compounds as claimed in claim 2 is characterized in that the used light source of described illumination is the tungsten incandescent light of natural light or 5～1000 watts.
4, the synthetic method of steroidal compounds as claimed in claim 2 is characterized in that described organic solvent is methylene dichloride, trichloromethane, tetracol phenixin, ethylene dichloride, ether, tetrahydrofuran (THF), 1,4-diox, benzene, toluene or acetonitrile.
CN 200610025049 2006-03-24 2006-03-24 Steroid C,D cycle rearrangement formed compounds Pending CN1821261A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103785339A (en) * 2013-11-28 2014-05-14 湖南科源生物制品有限公司 Photosensitized oxidation reaction equipment and application thereof
CN107814717A (en) * 2017-11-14 2018-03-20 中国科学院上海有机化学研究所 A kind of steroidal acetylenic acid compound, its synthetic method and purposes

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103785339A (en) * 2013-11-28 2014-05-14 湖南科源生物制品有限公司 Photosensitized oxidation reaction equipment and application thereof
CN103785339B (en) * 2013-11-28 2015-10-28 湖南科源生物制品有限公司 A kind of photosensitized oxidation consersion unit and application thereof
CN107814717A (en) * 2017-11-14 2018-03-20 中国科学院上海有机化学研究所 A kind of steroidal acetylenic acid compound, its synthetic method and purposes
CN107814717B (en) * 2017-11-14 2019-10-15 中国科学院上海有机化学研究所 A kind of steroidal acetylenic acid compound, its synthetic method and purposes

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