JPS6136510B2 - - Google Patents
Info
- Publication number
- JPS6136510B2 JPS6136510B2 JP53007406A JP740678A JPS6136510B2 JP S6136510 B2 JPS6136510 B2 JP S6136510B2 JP 53007406 A JP53007406 A JP 53007406A JP 740678 A JP740678 A JP 740678A JP S6136510 B2 JPS6136510 B2 JP S6136510B2
- Authority
- JP
- Japan
- Prior art keywords
- dihydroxyprovitamin
- spectrum
- compound
- ether
- etoh
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- -1 epoxide compounds Chemical class 0.000 description 4
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 238000001819 mass spectrum Methods 0.000 description 3
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 238000002211 ultraviolet spectrum Methods 0.000 description 2
- 239000011710 vitamin D Substances 0.000 description 2
- 229940046008 vitamin d Drugs 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 1
- 239000004593 Epoxy Substances 0.000 description 1
- 208000037147 Hypercalcaemia Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical class [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
- 230000003167 anti-vitamin Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 1
- 230000000148 hypercalcaemia Effects 0.000 description 1
- 208000030915 hypercalcemia disease Diseases 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- YUGCAAVRZWBXEQ-WHTXLNIXSA-N previtamin D3 Chemical compound C=1([C@@H]2CC[C@@H]([C@]2(CCC=1)C)[C@H](C)CCCC(C)C)\C=C/C1=C(C)CC[C@H](O)C1 YUGCAAVRZWBXEQ-WHTXLNIXSA-N 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 150000003710 vitamin D derivatives Chemical group 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Description
【発明の詳細な説明】
本発明は次式（）で示される１β・25−ジヒ
ドロキシビタミンD3に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to 1β·25-dihydroxyvitamin D 3 represented by the following formula ().
式（）で示される本発明の化合物は新規化合
物であり、例えば１β・25−ジヒドロキシプロビ
タミンD3を出発物質とし、以下これをビタミン
Ｄ骨格を合成するため通常用いられる手段である
紫外線照射によるステロイドのＢ環の開裂−異性
化という一連の反応に附すことにより製造され
る。なお、ここで１β・25−ジヒドロキシプロビ
タミンD3は特開昭51−100056号公報に記載の化
合物、すなわち１α・25−ジヒドロキシビタミン
D3を合成する際の中間副生物である１β・２β
−エポキシド化合物（）を水素化金属類、例え
ば水素化アルミニウムリチウムで還元することに
よつて製造される。 The compound of the present invention represented by the formula () is a new compound, for example, using 1β25-dihydroxyprovitamin D3 as a starting material, which is treated by ultraviolet irradiation, which is a commonly used means for synthesizing the vitamin D skeleton. It is produced by subjecting it to a series of reactions of cleavage and isomerization of the B ring of a steroid. Note that 1β・25-dihydroxyprovitamin D 3 is the compound described in JP-A-51-100056, that is, 1α・25-dihydroxyprovitamin D 3.
1β and 2β are intermediate by-products when synthesizing D3
- prepared by reducing epoxide compounds () with metal hydrides, such as lithium aluminum hydride.
このようにして得られた本発明の化合物（）
は抗ビタミンＤ作用を有し高カルシウム血症治療
剤として極めて有用である。 Compound of the present invention thus obtained ()
has an anti-vitamin D effect and is extremely useful as a therapeutic agent for hypercalcemia.
実施例 １
１β・２β−エポキシコレスタ−５・７−ジエ
ン−３β・25−ジオールと４−フニニル−１・
２・４−トリアゾン−３・５−ジオンの１・４−
環化付加体200mgを無水テトラヒドロフラン20ml
に溶解し、水素化アルミニウムリチウム200mgを
加え１時間穏かに還流煮沸させ、冷却後、飽和硫
酸ナトリウム水を加え過剰の水素化アルミニウム
リチウムを分解する。析出物を去し、液を硫
酸マグネシウムで乾燥し、溶媒を留去する。クロ
ロホルムを加え析出した結晶を取する。メタノ
ール・エーテルで再結晶１β・25−ジヒドロキシ
プロビタミンD348.1mgを得る。融点212〜214℃。Example 1 1β・2β-epoxy cholesta-5・7-diene-3β・25-diol and 4-funinyl-1・
1,4- of 2,4-triazone-3,5-dione
200 mg of cycloadduct in 20 ml of anhydrous tetrahydrofuran
Add 200 mg of lithium aluminum hydride and boil under gentle reflux for 1 hour. After cooling, add saturated sodium sulfate water to decompose excess lithium aluminum hydride. The precipitate was removed, the liquid was dried over magnesium sulfate, and the solvent was distilled off. Add chloroform and collect the precipitated crystals. Recrystallize with methanol ether to obtain 48.1 mg of 1β25-dihydroxyprovitamin D 3 . Melting point 212-214℃.
UVスペクトルλＥｔｏＨ ｎａｘ（ｎｍ）：295、283、27
2、
264
NMRスペクトル（δind6−DMSO）：0.55
（3H、ｓ）、0.89（3H、ｓ）、1.05（6H、ｓ）、
4.60（2H、ｍ）、5.24（1H、ｄ）、5.53（1H、
ｄ）
マススペクトル（ｍ／ｅ）：416（M+）、398、
380
IRスペクトル（cm-1、KBr）：3330、1660、1610
実施例 ２
１β・25−ジヒドロキシプロビタミンD335mg
をエーテル800mlに溶解し高圧水銀燈（400w）で
１分間20秒間バイコールフイルターを通して光照
射する。エーテルを留去し残渣をセフアデツクス
LH−20、20ｇを充填したカラムクロマトグラフ
イーに附しクロロホルム：ヘキサン（65：35）で
溶出し１β・25−ジヒドロキシプレビタミンD3
の分画を集めて濃縮する。収量7.63mg（ε：9000
としてUVで定量）。１β・25−ジヒドロキシプレ
ビタミンD3をエーテル中10日間室温で暗所に放
置後濃縮し、セフアデツクスLH−20、20ｇを充
填したカラムクロマトグラフイーに附しクロロホ
ルム：ヘキサン（65：35）で溶出し精製して油状
の１β・25−ジヒドロキシビタミンD34.99mgを得
る（ε：18000としてUVで定量）。UV spectrum λ EtoH nax (nm): 295, 283, 27
2,
264 NMR spectrum ( δind6 −DMSO): 0.55
(3H, s), 0.89 (3H, s), 1.05 (6H, s),
4.60 (2H, m), 5.24 (1H, d), 5.53 (1H,
d) Mass spectrum (m/e): 416 (M + ), 398,
380 IR spectrum (cm -1 , KBr): 3330, 1660, 1610 Example 2 1β・25-dihydroxyprovitamin D 3 35 mg
Dissolve in 800 ml of ether and irradiate with a high-pressure mercury lamp (400 W) for 1 minute and 20 seconds through a Vycor filter. Distill the ether and save the residue
Attach to column chromatography packed with 20g of LH-20 and elute with chloroform:hexane (65:35) to extract 1β25-dihydroxyprevitamin D3.
Collect and concentrate the fractions. Yield 7.63 mg (ε: 9000
quantified by UV). 1β・25-dihydroxy previtamin D 3 was left in the dark at room temperature for 10 days in ether, concentrated, applied to column chromatography packed with 20 g of Sephadex LH-20, and eluted with chloroform:hexane (65:35). The product is purified to obtain 4.99 mg of oily 1β·25-dihydroxyvitamin D 3 (determined by UV as ε: 18000).
UVスペクトルλＥｔｏＨ ｎａｘ（ｎｍ）：213、262
λＥｔｏＨ ｎｉｏ：226
マススペクトル（ｍ／ｅ）：416（M+）、398、
380UV spectrum λ EtoH nax (nm): 213, 262 λ EtoH nio : 226 Mass spectrum (m/e): 416 (M + ), 398,
380
図面は本発明の化合物（）のマススペクトル
である。なお、ｍ／e410以上はM+ピーク確認の
ため20倍に拡大してある。
The drawing is a mass spectrum of the compound () of the present invention. The images above m/e410 are magnified 20 times to confirm the M + peak.
Claims (1)
D3。[Claims] 1 formula 1β・25-dihydroxyvitamin represented by
D3 .
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP740678A JPS54103855A (en) | 1978-01-27 | 1978-01-27 | 1beta, 25-dihydroxyvitamin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP740678A JPS54103855A (en) | 1978-01-27 | 1978-01-27 | 1beta, 25-dihydroxyvitamin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS54103855A JPS54103855A (en) | 1979-08-15 |
| JPS6136510B2 true JPS6136510B2 (en) | 1986-08-19 |
Family
ID=11664982
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP740678A Granted JPS54103855A (en) | 1978-01-27 | 1978-01-27 | 1beta, 25-dihydroxyvitamin |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS54103855A (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5250523A (en) * | 1988-04-29 | 1993-10-05 | Wisconsin Alumni Research Foundation | Side chain unsaturated 1α-hydroxyvitanim D homologs |
| JP4910816B2 (en) * | 2007-03-26 | 2012-04-04 | 株式会社ジェイテクト | Measuring device for moving amount of rolling element and measuring method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3697559A (en) * | 1971-02-25 | 1972-10-10 | Wisconsin Alumni Res Found | 1,25-dihydroxycholecalciferol |
| JPS51100056A (en) * | 1975-02-28 | 1976-09-03 | Chugai Pharmaceutical Co Ltd | 1 arufua 255 jihidorokishikorekarushifuerooruno seiho |
-
1978
- 1978-01-27 JP JP740678A patent/JPS54103855A/en active Granted
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3697559A (en) * | 1971-02-25 | 1972-10-10 | Wisconsin Alumni Res Found | 1,25-dihydroxycholecalciferol |
| JPS51100056A (en) * | 1975-02-28 | 1976-09-03 | Chugai Pharmaceutical Co Ltd | 1 arufua 255 jihidorokishikorekarushifuerooruno seiho |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS54103855A (en) | 1979-08-15 |
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