JPH0267296A - Steroid compound - Google Patents
Steroid compoundInfo
- Publication number
- JPH0267296A JPH0267296A JP21953588A JP21953588A JPH0267296A JP H0267296 A JPH0267296 A JP H0267296A JP 21953588 A JP21953588 A JP 21953588A JP 21953588 A JP21953588 A JP 21953588A JP H0267296 A JPH0267296 A JP H0267296A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- formula
- reaction
- agent
- estradiol
- 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.)
- Pending
Links
- -1 Steroid compound Chemical class 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 17
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 6
- 239000000126 substance Substances 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 125000002252 acyl group Chemical group 0.000 claims description 3
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 abstract description 6
- 238000006243 chemical reaction Methods 0.000 abstract description 6
- 229960005309 estradiol Drugs 0.000 abstract description 5
- 229930182833 estradiol Natural products 0.000 abstract description 5
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 abstract description 4
- 239000012320 chlorinating reagent Substances 0.000 abstract description 4
- 239000003795 chemical substances by application Substances 0.000 abstract description 3
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 abstract description 2
- 206010028980 Neoplasm Diseases 0.000 abstract description 2
- 230000001419 dependent effect Effects 0.000 abstract description 2
- 239000000032 diagnostic agent Substances 0.000 abstract description 2
- 229940039227 diagnostic agent Drugs 0.000 abstract description 2
- 150000002148 esters Chemical class 0.000 abstract description 2
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 2
- 239000000463 material Substances 0.000 abstract description 2
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 abstract description 2
- 239000002253 acid Substances 0.000 abstract 1
- 125000001589 carboacyl group Chemical group 0.000 abstract 1
- 239000000460 chlorine Substances 0.000 abstract 1
- 229940088597 hormone Drugs 0.000 abstract 1
- 239000005556 hormone Substances 0.000 abstract 1
- 150000003431 steroids Chemical class 0.000 abstract 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- VIMMECPCYZXUCI-MIMFYIINSA-N (4s,6r)-6-[(1e)-4,4-bis(4-fluorophenyl)-3-(1-methyltetrazol-5-yl)buta-1,3-dienyl]-4-hydroxyoxan-2-one Chemical compound CN1N=NN=C1C(\C=C\[C@@H]1OC(=O)C[C@@H](O)C1)=C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 VIMMECPCYZXUCI-MIMFYIINSA-N 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- FANCTJAFZSYTIS-IQUVVAJASA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-7a-methyl-1-[(2r)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C\1C([C@@H](O)C[C@H](O)C/1)=C)C)CS(=N)(=O)C1=CC=CC=C1 FANCTJAFZSYTIS-IQUVVAJASA-N 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- YRIZYWQGELRKNT-UHFFFAOYSA-N 1,3,5-trichloro-1,3,5-triazinane-2,4,6-trione Chemical compound ClN1C(=O)N(Cl)C(=O)N(Cl)C1=O YRIZYWQGELRKNT-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000005660 chlorination reaction Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 229950009390 symclosene Drugs 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Substances ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 229960001701 chloroform Drugs 0.000 description 2
- 229940011871 estrogen Drugs 0.000 description 2
- 239000000262 estrogen Substances 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- HBENZIXOGRCSQN-VQWWACLZSA-N (1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-16-[(2S)-2-hydroxy-3,3-dimethylpentan-2-yl]-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol Chemical compound N1([C@@H]2CC=3C4=C(C(=CC=3)O)O[C@H]3[C@@]5(OC)CC[C@@]2([C@@]43CC1)C[C@@H]5[C@](C)(O)C(C)(C)CC)CC1CC1 HBENZIXOGRCSQN-VQWWACLZSA-N 0.000 description 1
- SHAHPWSYJFYMRX-GDLCADMTSA-N (2S)-2-(4-{[(1R,2S)-2-hydroxycyclopentyl]methyl}phenyl)propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C[C@@H]1[C@@H](O)CCC1 SHAHPWSYJFYMRX-GDLCADMTSA-N 0.000 description 1
- VUDZSIYXZUYWSC-DBRKOABJSA-N (4r)-1-[(2r,4r,5r)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one Chemical compound FC1(F)[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)N[C@H](O)CC1 VUDZSIYXZUYWSC-DBRKOABJSA-N 0.000 description 1
- GCBCRGZIRHMTNJ-YVRXZLTFSA-N (8R,9S,13S,14S)-2-chloro-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol Chemical compound ClC=1C(=CC2=C([C@H]3CC[C@@]4(C(CC[C@H]4[C@@H]3CC2)O)C)C=1)O GCBCRGZIRHMTNJ-YVRXZLTFSA-N 0.000 description 1
- MHSLDASSAFCCDO-UHFFFAOYSA-N 1-(5-tert-butyl-2-methylpyrazol-3-yl)-3-(4-pyridin-4-yloxyphenyl)urea Chemical compound CN1N=C(C(C)(C)C)C=C1NC(=O)NC(C=C1)=CC=C1OC1=CC=NC=C1 MHSLDASSAFCCDO-UHFFFAOYSA-N 0.000 description 1
- QHGRSOANCKBFMK-KWYCKUBMSA-N ClC=1C2=C([C@H]3CC[C@@]4(C(CC[C@H]4[C@@H]3CC2)O)C)C=CC=1O Chemical compound ClC=1C2=C([C@H]3CC[C@@]4(C(CC[C@H]4[C@@H]3CC2)O)C)C=CC=1O QHGRSOANCKBFMK-KWYCKUBMSA-N 0.000 description 1
- 241000737241 Cocos Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- YLEIFZAVNWDOBM-ZTNXSLBXSA-N ac1l9hc7 Chemical compound C([C@H]12)C[C@@H](C([C@@H](O)CC3)(C)C)[C@@]43C[C@@]14CC[C@@]1(C)[C@@]2(C)C[C@@H]2O[C@]3(O)[C@H](O)C(C)(C)O[C@@H]3[C@@H](C)[C@H]12 YLEIFZAVNWDOBM-ZTNXSLBXSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 210000000554 iris Anatomy 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229940072033 potash Drugs 0.000 description 1
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- 238000006042 reductive dechlorination reaction Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 229940035339 tri-chlor Drugs 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Landscapes
- Investigating Or Analysing Biological Materials (AREA)
- Steroid Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
本発明はステロイド化合物、特に塩素化エストロゲン誘
導体に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to steroid compounds, particularly chlorinated estrogen derivatives.
本発明の塩素化エストロゲン誘導体は次の式で表される
新規物質であって、ステロイド性ホルモン依存性の腫瘍
に対する治療における検査薬もしくは診断薬あるいはそ
れらの製造中間体として有用なものである；
ｒ
（式中、Ｒは水素原子または低級アルカノイル基Ｒ′お
よび Ｒ＃はそれぞれ水素原子または塩素原子を表す、
ただし、式＋ １１ ）において、ＲノとＲ′の少な（
ともいずれか一方は塩素原子を表↑ 、 ）
化合物（Ｉ）および（ＩＩ ）は、式：（式中、Ｒは前
記と同１！異である。）で示される対応するエストラジ
オールまたはそのニスデルを塩素化して化合物（Ｉ）を
得、これを還元的脱塩素化することによって化合物（■
）とすることにより製造される。The chlorinated estrogen derivative of the present invention is a new substance represented by the following formula, and is useful as a test agent or diagnostic agent in the treatment of steroid hormone-dependent tumors, or as an intermediate for their production; r (In the formula, R is a hydrogen atom or a lower alkanoyl group R' and R# each represent a hydrogen atom or a chlorine atom,
However, in formula + 11), if R and R' are small (
and either one represents a chlorine atom ↑ , ) Compounds (I) and (II) contain the corresponding estradiol or its nisdel represented by the formula: (wherein R is the same as above and 1 different!) The compound (I) is obtained by chlorination, and the compound (■
).
塩素化はエストラジオールまたはそのエステル（ＩＩＩ
１に対し、塩素化剤（たとえばＮ−クロロサクシンイ
ミド、トリクロロイソシアヌール酸、塩化スルフリル、
塩素ガス）を反応さけることによって行うことができる
１反応は通常はエタノールｔ−ツクノール、酢酸、アセ
トニトリルなどの不活性溶媒中で行うのが好ましい。Chlorination is estradiol or its ester (III
1, chlorinating agents (e.g. N-chlorosuccinimide, trichloroisocyanuric acid, sulfuryl chloride,
One reaction that can be carried out by avoiding the reaction (chlorine gas) is usually preferably carried out in an inert solvent such as ethanol tertiary alcohol, acetic acid, or acetonitrile.
還元的脱塩素化は化合物（１）に対し、不活性溶媒中、
水素化金属（たとえば水素化ホウ素ナトリウム）や亜鉛
末−アルコールのような還元剤を作用させるか、パラジ
ウム触媒を使用する接触還元によってこれを行うことが
できる。Reductive dechlorination is performed on compound (1) in an inert solvent,
This can be accomplished by the action of a reducing agent such as a metal hydride (for example sodium borohydride) or zinc dust-alcohol, or by catalytic reduction using a palladium catalyst.
上記の塩素化反応において、通常は１０−クロル体、２
．４．１０−トリクロル体、２、ｌＯ−ジクロル体およ
び４．１０−ジクロル体の混合物が得られるが、塩素化
剤、反応溶媒、反応条件などを適宜に選択することによ
って、これら４ｉ１の化合物のうちの１種またはそれ以
上の主成績体として生成せしめることができる。いずれ
の場合も、反応混合物に対し自体常套の分離精製手段を
適用することによって容易に各反応成績体を採取するこ
とが可能である。In the above chlorination reaction, the 10-chloro form, the 2-chloro form,
．． A mixture of 4.10-trichlor, 2,1O-dichlor and 4.10-dichlor is obtained, but by appropriately selecting the chlorinating agent, reaction solvent, reaction conditions, etc., these 4i1 compounds can be One or more of them can be produced as the main product. In either case, each reaction product can be easily collected by applying conventional separation and purification means to the reaction mixture.
以下に実施例を挙げて本発明化合物＋１）＋３よび（ｎ
ｌの具体的な製造法を説明する。Examples are given below, and compounds of the present invention +1)+3 and (n
A specific manufacturing method of l will be explained.
融点は清水融点測定器によって測定され、未補正値で示
した。赤外線スペクトルは傘ジャスニーＡ−７０２分光
器、 ＋Ｈ磁気共鳴スペクトル０は Ｖａｒ−ｉａｎ
ＸＬ−２００分光器、ＩＣ化学シフト値６はＶａｒｉａ
ｎＸＬ−１ｏｏ−１２分光器テ測定した。（＊：ｆｉ定
溶媒は重クロロホルム、モしてＭｅ４Ｓｉの波数を挿入
した波数を基準値とした。）質咀スペクトルは、日立舅
６δ分光器、旋光度はパーキンエルマー社旋光計２４１
が用いられた。Melting points were determined using a Shimizu melting point meter and are shown as uncorrected values. Infrared spectrum is Umbrella Jasny A-702 spectrometer, +H magnetic resonance spectrum 0 is Var-ian
XL-200 spectrometer, IC chemical shift value 6 is Varia
Measurements were made using an nXL-1oo-12 spectrometer. (*: The fi constant solvent was deuterated chloroform, and the wave number inserted with the wave number of Me4Si was used as the reference value.) The material spectrum was measured using a Hitachi 6δ spectrometer, and the optical rotation was measured using a PerkinElmer polarimeter 241.
was used.
生成物の分離精製はｌ□ｂａｒ加圧クロ加圧クロマトラ
製： Ｌｉｃｈｒｏｐｒｅｐ ｓｉ ６０、サイズ Ａ
、（２４０〜ｌ０ｍ５．４３〜６３ｕ ｍ ） ：サ
イズ Ｂ、（３１Ｇ 〜２５１ｍ、 ４３〜６３ｇ ｍ
） 、サイズＣ１（４４０〜３７ｍｍ、６３〜１２５
μ−を目的に応じ、使用した０元素分析値は総て、計算
値より±０３％の語差範囲内でありＳＵＰ、Ｎｏ、５６
７１５としてデーターバンクに収蔵されている。英国化
学会誌パーキン輯
なお、実施例中における化合物番号は次のものを表わす
：
番 号 式 ＲＲ’ Ｒ”ｌ
ａ ＩＩＩ Ｈｌ ｂ
ＩＩＩ Ｃ０ＣＨｓ２ａ
ｌ ＨＨ）＋２ ｂ Ｉ
Ｃ０ＣＨｓ ＨＨ３ａ Ｉ
ＨＣＬ Ｈ３ｂ Ｉ
Ｃ０ＣＨ，α Ｈ４ａ ｒ
ＨＨＩＪ
４ｂ ｌ Ｃ０ＣＨ，）Ｉ Ｃ
Ｉ５ ａ Ｉ ＨＣＩ
ＣＬ５ｂＩ Ｃ０ＣＨｓ ＣＬ
ＣＩ６ ａ ＩＩ ＨＣｊ／Ｈ６ｂ
ＩＩ ＣＯＣｌ１． ＣＩ
Ｈ７ａ ＩＩ ＨＨＣｊ
７ｂ ＩＩ ｃｏｃｏｓ Ｈｌｊ
８ ａ ＩＩ ＨＣＬ α８ｂ
ＩＴ ＣＯＣＨｍ ＣＬ
ＣＬｍユ
エストラジオール（化合物１ａ） （５ｇ）をアセト
ニトリル（２０Ｇ＋ｓｌ）中に溶かし、水冷下にトリク
ロロイソシアヌール酸（２，１ｇ）を−度に加え、３０
分間放置する０反応の終了を確認しくデンプン−法度カ
リ試９紙、陰性）、反応混合物は氷水中に注ぎ、生成物
は塩化メチレンで抽出する。塩化メチレン層は曲硫酸水
素ナトリウム５％溶液、炭酸ソーダ飽和水溶液ついで水
洗後乾燥する。（無水硫酸ソーダ）、得られた油状物質
は”Ｌｎｂａｒカラム（サイズＣ）を用い、分離精製す
ると先ずトルエン−酢酸エチル（９：１ ）で溶出され
る画分より化合物５ａ （１，３％、２５％）が得られ
る。ついで化合物３ａと化合物４ａの混合物を含む一分
の溶出がみられる。 （’ Ｈｎ、ｍ、ｒ、測定でｌ
：ｌの混合物であり、化合物３ａと化合物４ａは別途で
クロマト分離した。）化合物３ａと化合物４ａはそれぞ
れ６〜７％）極性の強い両分より、化合物２ａ （１，
１ｇ ： ２０％）が溶出された。Separation and purification of the product is carried out using Lichroprep si 60, size A, manufactured by Lichroprep SI 60, size A.
, (240-10m 5.43-63um): Size B, (31G-251m, 43-63g m
), size C1 (440-37mm, 63-125
Depending on the purpose of μ-, all the zero element analysis values used were within the range of ±03% word difference from the calculated value, SUP, No. 56
It is stored in the data bank as 715. In addition, the compound numbers in the examples represent the following: Number Formula RR' R”l
a III Hl b
III C0CHs2a
l HH)+2 b I
C0CHs HH3a I
HCL H3b I
C0CH, α H4a r
HHIJ 4b l C0CH,)IC
I5 a I HCI
CL5bI C0CHs CL
CI6 a II HCj/H6b
II COCl1. C.I.
H7a II HHCj 7b II cocos Hlj
8 a II HCL α8b
IT COCHm CL
CLm euestradiol (compound 1a) (5 g) was dissolved in acetonitrile (20 G + sl), and trichloroisocyanuric acid (2.1 g) was added to -30° C. under water cooling.
Leave to stand for 0 minutes to confirm completion of the reaction (starch-potash test 9 paper, negative), pour the reaction mixture into ice water and extract the product with methylene chloride. The methylene chloride layer is washed with a 5% sodium bisulfate solution and a saturated aqueous solution of sodium carbonate, then washed with water, and then dried. (anhydrous sodium sulfate), and the obtained oily substance was separated and purified using a Lnbar column (size C). Compound 5a (1.3%, 25%) is obtained. Then, a minute elution containing a mixture of compound 3a and compound 4a is observed. (' Hn, m, r, l in the measurement
:l mixture, and compound 3a and compound 4a were separately chromatographically separated. )Compound 3a and compound 4a are each 6-7%) Compound 2a (1,
1 g: 20%) was eluted.
上記化合物２ａ〜５ａの物性は第１表に示すとおりであ
る。The physical properties of the above compounds 2a to 5a are as shown in Table 1.
１」Ｌ」Ｌｌ
塩素化剤としてトリクロロイソシアヌール酸の代りに、
＋１−クロロスクミンイミドを使用し、８０〜８５℃で
２時間反応させる以外は実施例１と同様に操作して、化
合物２８〜５ａを得た。1"L"Ll Instead of trichloroisocyanuric acid as the chlorinating agent,
Compounds 28-5a were obtained in the same manner as in Example 1, except that +1-chloroscumimide was used and the reaction was carried out at 80 to 85°C for 2 hours.
Ｌｌｌ」
エストラジオール（化合物１ａ）の代りにニストランオ
ール １７−アセテート（化合物１ｂ）を使用する以外
は実権例１と同様に操作して、化合物２ｂ〜５ｂを得た
。Compounds 2b to 5b were obtained in the same manner as in Example 1 except that nistranol 17-acetate (compound 1b) was used instead of estradiol (compound 1a).
１０ＩＡ
化合物（１）がら化合物（１１）を製造する一般的な方
法としては、化合物（１）の９９％エタノール溶液に過
剰の水素化ホウ素ナトリウムを撹拌しつつ’１４で加え
る。水素ガスの発生がみられ、！Ｑ１１ｉしていた物質
もとけ、透明な溶液となる。酢酸水７１１液を２．３
（Ｒ下し、未反応の水素化ホウ禦ナトリウムを分解し、
水で希釈凌、生成物は塩化メチレンで抽出し、シリカジ
ェルクロマト（トルエン：酢酸エチル δ：ＩでｙＩ開
）で分離精製して得る。10IA A general method for producing compound (11) from compound (1) is to add excess sodium borohydride to a 99% ethanol solution of compound (1) with stirring. Generation of hydrogen gas was observed! The Q11i substance also dissolves and becomes a transparent solution. 2.3 711 liquid acetic acid
(Reduced R, decomposed unreacted sodium borohydride,
After dilution with water, the product was extracted with methylene chloride and purified by silica gel chromatography (toluene:ethyl acetate δ:I open).
）２−クロルエストラジオール（化合物６１％）化合物
３ａ （１５０” ｌを水素化ホウ素ナトリウム（４３
−１１）と反応させ得られたガム状物質を分離精製する
と（クロマトグラフィー）、得られる。融点２７〜２７
３℃、収量７０”、 Ｎ關Ｒ・δ、０．７８（３Ｈ９Ｓ
、１８−Ｍｅ ｌ ： ６．７３（ＩＩ＋、 ３．４
−Ｈ） 、 ７．３３（１−ＨＩＨＩ
ｉｉ） ４−クロルエストラジオール（化合物７ａｊ化
合物４ａ （７０”）を水禦化ホつ素ナトリウム（２０
”）と反応させて得られたガム状物質を分離精製すると
（クロマトグラフィー）、得られる。融点２５３°〜２
５５℃、収ｆｉ ３５”ｇ、 ＮＩＩＲ：δ、 ０．７
９ （３８゜Ｓ、ｌδ−Ｍｅ ） ： ３．６８ｆｌ
Ｈ，ｔ、Ｊ２Ｈｚ、 １７ａ −Ｈ） ； ６゜δ２
（１８，ｄ９）１ｚ、 ２−）１ ） 、 ７．１５
（１）１． ｄ、Ｊ９Ｈｚ、 １８ｉｉｉ ） ２．
４−ジクロルエストラジオール（化合物Ｍａｌ化合物５
ａ （７０“菖）と反応させ得られたガム状物質を分離
精製すると（クロマトグラフィー）得られる、融点２０
８′〜２１０℃、収量２１”、 ＮｌｌＲ２δ、 ０．
８３ （３１１，Ｓ、ｔ８−Ｍｅ ） 、 ７．２６
（ＩＨ，Ｓ、１４）。この際副生するものとして４−ク
ロルニストランオール（８ｂｌ ： ２５″ａ１：エ
ストラジオール（ｌｂ）：ＩＳ”が確認された。) 2-Chlorestradiol (compound 61%) Compound 3a (150” l was dissolved in sodium borohydride (43%)
-11) by separating and purifying the resulting gummy substance (chromatography). Melting point 27-27
3℃, yield 70", N ratio δ, 0.78 (3H9S
, 18-Mel: 6.73 (II+, 3.4
-H), 7.33 (1-HIHI ii) 4-Chlorestradiol (compound 7aj compound 4a (70”)
It is obtained by separating and purifying (chromatography) the gummy substance obtained by reacting with ``). Melting point 253° ~ 2
55℃, yield 35”g, NIIR: δ, 0.7
9 (38°S, lδ-Me): 3.68fl
H, t, J2Hz, 17a -H); 6゜δ2
(18, d9)1z, 2-)1), 7.15
(1)1. d, J9Hz, 18iii) 2.
4-dichloroestradiol (compound Mal compound 5
When the gummy substance obtained by reacting with a (70" irises) is separated and purified (chromatography), it is obtained with a melting point of 20
8′-210°C, yield 21”, NllR2δ, 0.
83 (311,S, t8-Me), 7.26
(IH, S, 14). At this time, 4-chlornistranol (8bl: 25''a1:estradiol (lb):IS'') was confirmed as a by-product.
ＬＬ上」
化合物４ａ（１１，１ｇ ｌをエタノール＋１０”）中
で亜鉛末（希塩酸で洗浄し使用する。 ２００” ）を
加え還流！沸する。（１５分間）得られた固形物質は分
離精製するとくクロマトグラフィー璽化合物７ａ （７
３”）が得られた。標品、 ｔ、１．ｃおよびｉ、ｒス
ペクトルが一致することをｆＮ認した。この場合エタノ
ールの代りに酢酸を用いる系では、１７β水酸基が１部
アセチル化され、不利である。Add zinc dust (washed with dilute hydrochloric acid before use. 200") in Compound 4a (11.1g 1 in ethanol + 10") and reflux! Boil. (15 minutes) The obtained solid substance should be separated and purified by chromatography. Compound 7a (7
3") was obtained. It was confirmed that the standard, t, 1.c, and i, r spectra matched. In this case, in the system using acetic acid instead of ethanol, the 17β hydroxyl group was partially acetylated. , is disadvantageous.
Claims (1)
よびＲ″はそれぞれ水素原子または塩素原子を表す。）
で示される化合物。 ２、式： ▲数式、化学式、表等があります▼ （式中、Ｒは水素原子または低級アルカノイル基、Ｒ′
およびＲ″はそれぞれ水素原子または塩素原子を表わす
。ただし、Ｒ′とＲ″の少なくともいずれか一方は塩素
原子を表す。） で示される化合物。[Claims] 1. Formulas: ▲ Numerical formulas, chemical formulas, tables, etc.▼ (In the formula, R is a hydrogen atom or a lower alkanoyl group, and R' and R'' each represent a hydrogen atom or a chlorine atom.)
The compound shown in 2. Formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R is a hydrogen atom or a lower alkanoyl group, R'
and R'' each represent a hydrogen atom or a chlorine atom. However, at least one of R' and R'' represents a chlorine atom. ).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP21953588A JPH0267296A (en) | 1988-09-01 | 1988-09-01 | Steroid compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP21953588A JPH0267296A (en) | 1988-09-01 | 1988-09-01 | Steroid compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0267296A true JPH0267296A (en) | 1990-03-07 |
Family
ID=16737007
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP21953588A Pending JPH0267296A (en) | 1988-09-01 | 1988-09-01 | Steroid compound |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0267296A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0683237A4 (en) * | 1993-12-03 | 1998-07-29 | Snow Brand Milk Products Co Ltd | Method of examining hormone-dependent tumor. |
-
1988
- 1988-09-01 JP JP21953588A patent/JPH0267296A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0683237A4 (en) * | 1993-12-03 | 1998-07-29 | Snow Brand Milk Products Co Ltd | Method of examining hormone-dependent tumor. |
| US5914227A (en) * | 1993-12-03 | 1999-06-22 | Nakamura; Junji | Method for examination of hormone-dependent tumors |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Greeley | Rapid esterification for gas chromatography | |
| CN105237536A (en) | Substituted heterocycle fused gamma-carbolines solid | |
| Cope et al. | Cyclic Polyolefins. XIV. 3, 7-Dibromo-1, 2, 5, 6-Dibenzcycloöctadiene and 1, 2, 5, 6-Dibenzcycloöctatetraene | |
| Cohen | Dexamethasone | |
| Smith et al. | Optically active amines. XII. Synthesis and spectral properties some optically active. alpha.-oximino ketones and. alpha.-amino ketone hydrochlorides. Dimerization of. alpha.-amino ketones | |
| JPH03178977A (en) | Diterpene lactone compound and its preparation | |
| Meltzer et al. | A regioselective route to gossypol analogs: the synthesis of gossypol and 5, 5'-didesisopropyl-5, 5'-diethyl gossypol | |
| EP0089377B1 (en) | Novel steroid saponins, process for their extraction, and process for preparing 16-dehydropregnenolone therefrom | |
| Johnson et al. | Determination of stigmasterol in soybean sterol mixtures by infrared method | |
| Hudlicky et al. | Improved synthesis and characterization of pictet-spengler adducts of phenylpyruvic acid and biogenic amines | |
| JPH0267296A (en) | Steroid compound | |
| JPH0533955B2 (en) | ||
| JP3466527B2 (en) | New aconitine compounds and analgesic / anti-inflammatory agents | |
| Winkley | The synthesis of the α-d-anomers of “homonucleosides”: derivatives of 2, 5-anhydro-d-altritol | |
| Al-Yahya et al. | Noscapine | |
| DE112016004993T5 (en) | PROCESS FOR THE PREPARATION OF 17β-HYDROXY-DES-A-ANDROST-9,10-EN-5-ON | |
| NAMBARA et al. | Conformational analysis of epimeric 16-bromo-13α-estrones | |
| Klimstra et al. | Hypocholesterolemic Agents. II. 1 2β-Halo-5α-androstane Derivatives | |
| Bird et al. | Structures of the steroidal alkaloids 25-isosolafloridine and solacallinidine isolated from Solanum callium | |
| Fujimoto et al. | A Preparation of β-Sitosterol1a | |
| Tamura et al. | Stereochemistry and base-catalyzed rearrangement of 9-phenylthioxanthene-N-(p-toluenesulfonyl) sulfilimine | |
| Goeckner et al. | Reaction of cyanide ion with carbonyl compounds in dipolar aprotic solvents | |
| JPS63145296A (en) | Production of 5-trifluoromethyl-2'-deoxy-beta-uridines | |
| Bielefeld et al. | Preparation of 3. beta.-acetoxy-17. beta.-hydroxy-5. alpha.-androstane-16. alpha.-propionic acid. delta.-lactone | |
| Coombs et al. | A convenient preparation of high specific activity tritiated estrogens |