JPH02115184A - Production of dc-88a - Google Patents
Production of dc-88aInfo
- Publication number
- JPH02115184A JPH02115184A JP26558388A JP26558388A JPH02115184A JP H02115184 A JPH02115184 A JP H02115184A JP 26558388 A JP26558388 A JP 26558388A JP 26558388 A JP26558388 A JP 26558388A JP H02115184 A JPH02115184 A JP H02115184A
- Authority
- JP
- Japan
- Prior art keywords
- single bond
- compound
- base
- silver
- silver salt
- 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.)
- Granted
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 10
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 claims abstract description 5
- AZVARJHZBXHUSO-DZQVEHCYSA-N methyl (1R,4R,12S)-4-methyl-3,7-dioxo-10-(5,6,7-trimethoxy-1H-indole-2-carbonyl)-5,10-diazatetracyclo[7.4.0.01,12.02,6]trideca-2(6),8-diene-4-carboxylate Chemical compound COC1=C(OC)C(OC)=C2NC(C(=O)N3C[C@H]4C[C@]44C5=C(C(C=C43)=O)N[C@@](C5=O)(C)C(=O)OC)=CC2=C1 AZVARJHZBXHUSO-DZQVEHCYSA-N 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 2
- 239000003242 anti bacterial agent Substances 0.000 abstract description 4
- 239000002246 antineoplastic agent Substances 0.000 abstract description 4
- 238000006243 chemical reaction Methods 0.000 abstract description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 abstract description 4
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 abstract description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 abstract description 2
- 229910001961 silver nitrate Inorganic materials 0.000 abstract description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 abstract 3
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 abstract 1
- AOJDZKCUAATBGE-UHFFFAOYSA-N bromomethane Chemical compound Br[CH2] AOJDZKCUAATBGE-UHFFFAOYSA-N 0.000 abstract 1
- WBLIXGSTEMXDSM-UHFFFAOYSA-N chloromethane Chemical compound Cl[CH2] WBLIXGSTEMXDSM-UHFFFAOYSA-N 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 230000000844 anti-bacterial effect Effects 0.000 description 4
- 239000012442 inert solvent Substances 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000007979 citrate buffer Substances 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-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
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- UQPQXFUURNIVNJ-UHFFFAOYSA-N duocarmycin B2 Natural products COC1=C(OC)C(OC)=C2NC(C(=O)N3CC(CBr)C=4C5=C(C(=CC=43)O)NC(C5=O)(C)C(=O)OC)=CC2=C1 UQPQXFUURNIVNJ-UHFFFAOYSA-N 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- RBWNDBNSJFCLBZ-UHFFFAOYSA-N 7-methyl-5,6,7,8-tetrahydro-3h-[1]benzothiolo[2,3-d]pyrimidine-4-thione Chemical compound N1=CNC(=S)C2=C1SC1=C2CCC(C)C1 RBWNDBNSJFCLBZ-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000028018 Lymphocytic leukaemia Diseases 0.000 description 1
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-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
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 208000003747 lymphoid leukemia Diseases 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000004237 preparative chromatography Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 description 1
- 229910001958 silver carbonate Inorganic materials 0.000 description 1
- SDLBJIZEEMKQKY-UHFFFAOYSA-M silver chlorate Chemical compound [Ag+].[O-]Cl(=O)=O SDLBJIZEEMKQKY-UHFFFAOYSA-M 0.000 description 1
- 229910001923 silver oxide Inorganic materials 0.000 description 1
- -1 silver tetrafluoroborate Chemical compound 0.000 description 1
- 229910001494 silver tetrafluoroborate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
Abstract
Description
【発明の詳細な説明】 り業上二肌且分■ 本発明は、ＤＣ−８８Ａの製造法に関する。[Detailed description of the invention] Two years of experience in the industry■ The present invention relates to a method for manufacturing DC-88A.
ＤＣ−８８Ａは抗菌活性及び抗腫瘍活性を有し、抗菌剤
及び抗腫瘍剤として有用である。DC-88A has antibacterial and antitumor activity and is useful as an antibacterial and antitumor agent.
従来Ω且血
ＤＣ−８８Ａは、ストレプトマイセス層に属する微生物
が生産する物質であり、各種細菌に抗菌活性を示すほか
、リンホサイティック・リューケミアＰ３８８等に抗腫
瘍活性を示すことがＷＯ３７１０６２６５に開示されて
いる。Conventional Ω and blood DC-88A is a substance produced by microorganisms belonging to the Streptomyces layer, and in addition to exhibiting antibacterial activity against various bacteria, WO37106265 has shown that it also exhibits antitumor activity against Lymphocytic leukemia P388, etc. Disclosed.
ＤＣ−８８Ａは下記の構造を有する。DC-88A has the following structure.
＜”° しよ゛ る
抗菌剤及び抗腫瘍剤として有用なりＣ−８８Ａの新規な
製造法は常に求められている。There is a constant need for new methods of producing C-88A, which is useful as an antibacterial and antitumor agent.
１・ ′″２ るための
本発明は、−最大（■）：
（式中、Ｘは単結合または−ＣＩ＋□−であり、χが単
結合の場合ＹはＣＨ，ＢｒまたはＣＨ２１であり、Ｘが
−ＣＨ２−の場合ＹはＢｒまたはＣ１である。）で表わ
される化合物に、塩基あるいは銀塩を反応させることに
より、ＤＣ−８８Ａを得ることを特徴とするＤＣ−８８
Ａの製造法に関する。1・ ′″2 The present invention for -maximum (■): (wherein, X is a single bond or -CI+□-, and when χ is a single bond, Y is CH, Br or CH21, DC-88A is obtained by reacting a compound represented by (when X is -CH2-, Y is Br or C1) with a base or a silver salt.
Regarding the manufacturing method of A.
−最大（１）において、Ｘが単結合でＹがＣＨ２Ｃｆで
ある化合物をＤＣ−８９Ａ１、Ｘが単結合でＹがＣＨｚ
Ｂｒである化合物をＤＣ−８９８１ＳＸが−ＣＨｔ −
でＹがＣｆである化合物をＤＣ−８９Ａ２、Ｘが−ＣＨ
，−でＹがＢｒである化合物をＤＣ−８９８２と称する
。- In maximum (1), the compound where X is a single bond and Y is CH2Cf is DC-89A1, and the compound where X is a single bond and Y is CHz
When DC-8981SX converts a compound that is Br to -CHt -
The compound in which Y is Cf is DC-89A2, and X is -CH
, - in which Y is Br is referred to as DC-8982.
ＤＣ−８９Ａ１．ＤＣ−８９Ａ２．ＤＣ−８９８１また
はＤＣ−８９Ｂ２あるいはそれらの混合物を不活性溶媒
中、塩基と反応させることによりＤＣ−８８Ａを製造す
ることができる。不活性溶媒としてアセトニトリル、ジ
メチルホルムアミド、塩化メチレン、ジメチルスルホキ
シド、ピリジン、ヘキサメチルホスホリックトリアミド
、ベンゼン。DC-89A1. DC-89A2. DC-88A can be prepared by reacting DC-8981 or DC-89B2 or a mixture thereof with a base in an inert solvent. Acetonitrile, dimethylformamide, methylene chloride, dimethyl sulfoxide, pyridine, hexamethylphosphoric triamide, benzene as inert solvents.
トルエン、テトラヒドロフラン等が、単独あるいは混合
して用いられる。塩基としては、１．８−ジアザビシク
ロＣ５，４，０３ウンデカ−７−エン、１゜４−ジアザ
ビシクロ（２，２，２〕オクタン、 １．５−ジアザビ
シクロ（４，３，０Ｅノナ−５−エン、カリウムＬ−ブ
トキシド、炭酸カリウム、炭酸ナトリウム、炭酸水素ナ
トリウム、水素化ナトリウム。Toluene, tetrahydrofuran, etc. may be used alone or in combination. As the base, 1.8-diazabicycloC5,4,03undec-7-ene, 1゜4-diazabicyclo(2,2,2]octane, 1.5-diazabicyclo(4,3,0Enon-5-ene) , potassium L-butoxide, potassium carbonate, sodium carbonate, sodium bicarbonate, sodium hydride.
ナトリウムメトキシド、トリエチルアミン、ジイソプロ
ピルエチルアミン、ジメチルアニリン、ジメチルアミノ
ピリジン等が包含され、通常ＤＣ−８９八１． ＤＣ
−８９Ａ２． ＤＣ−８９８１，ＤＣ−８９８２に
対して１〜，１．５当量用いられる。反応は通常−２０
〜５０゛Ｃで行い２０分〜５時間で終了する。These include sodium methoxide, triethylamine, diisopropylethylamine, dimethylaniline, dimethylaminopyridine, etc., and are usually DC-8981. D.C.
-89A2. 1 to 1.5 equivalents are used for DC-8981 and DC-8982. The reaction is usually -20
It is carried out at ~50°C and completed in 20 minutes to 5 hours.
またＤＣ−８９Ａ１．ＤＣ−８９Ａ２．ＤＣ−８９８１
゜ＤＣ−８９８２を不活性溶媒とｐＨ５〜７の緩衝液と
の混合溶媒中、銀塩と反応させることによりＤＣ−８８
Ａを製造することができる。不活性溶媒としてアセトニ
トリル、テトラヒドロフラン、ジメチルホルムアミド、
ジメチルスルホキシド、メタノール、エタノール等を包
含し、単独あるいは混合して用いられる。ｐＨ５〜７の
緩衝液としては０、０２ Ｍ〜ＩＭのリン酸緩衝液、ク
エン酸緩衝液等が用いられる。銀塩として硝酸銀、炭酸
銀、酸化銀、塩素酸銀、過塩素酸銀、四フフ化ホウ素酸
銀等が包含され、通常ＤＣ−８９Ａ１． ＤＣ−８９Ａ
２゜ＤＣ−８９８１，ＤＣ−８９８２に対して１〜５当
量用いられる。反応は通常Ｏ〜８０″Ｃで行い、３０分
〜２日で終了する。Also DC-89A1. DC-89A2. DC-8981
゜DC-88 is produced by reacting DC-8982 with a silver salt in a mixed solvent of an inert solvent and a buffer solution of pH 5 to 7.
A can be manufactured. Acetonitrile, tetrahydrofuran, dimethylformamide, as an inert solvent
It includes dimethyl sulfoxide, methanol, ethanol, etc., and can be used alone or in combination. As the buffer having a pH of 5 to 7, 0.02M to IM phosphate buffer, citrate buffer, etc. are used. Silver salts include silver nitrate, silver carbonate, silver oxide, silver chlorate, silver perchlorate, silver tetrafluoroborate, etc., and are usually used as DC-89A1. DC-89A
1 to 5 equivalents are used relative to 2°DC-8981 and DC-8982. The reaction is usually carried out at 0 to 80''C and is completed in 30 minutes to 2 days.
各工程の反応終了後、必要に応じて緩衝液、水等を加え
、酢酸エチル、クロロホルム、エーテル等の非水溶性溶
媒で抽出する。水、食塩水等で洗浄後、無水硫酸す１ヘ
リウム等で乾燥し、溶媒を留去する。残渣をシリカゲル
クロマトグラフィー８層クロマトグラフィー、高速液体
分取りロマトグラフィー、再結晶等により精製を行う。After the reaction in each step is completed, a buffer solution, water, etc. are added as necessary, and extraction is performed with a non-aqueous solvent such as ethyl acetate, chloroform, or ether. After washing with water, saline, etc., drying with anhydrous sulfuric acid (1 helium), etc., and distilling off the solvent. The residue is purified by 8-layer silica gel chromatography, high performance liquid preparative chromatography, recrystallization, etc.
次に本発明の実施例をあげる。Next, examples of the present invention will be given.
実施例Ｉ ＤＣ〜８９Ｂ２からＤＣ−８８Ａの合成り
Ｃ−８９Ｂ２ （５０ｍｇ： ｏ、ｏ ８５ ｍｍｏｆ
）をア・≧トニトリル（１０ｍｆ）に？容解し、１．８
−ジアザビシクロ（５，４，０）ウンデカ−７−ニン１
３．３μ２を加え、室温で４５分間撹拌した。０．１Ｍ
のクエン酸緩衝液（ｐ）１４ ） １０ ｍＩ！、を加
え、酢酸エチルで抽出した。飽和食塩水で洗浄し、無水
硫酸ナトリウムで乾燥後溶媒を留去して、粗生成物４７
ｍｇを得た。これをシリカゲルカラムクロマトグラフィ
ー（ワコーゲルＣ２００１０ｍ７！、クロロホルム：ア
セトン−１：０〜５０：１で溶出）で精製しＤＣ−８８
Ａ３５．８ｍｇ （収率８３％）を得た。Example I Synthesis of DC-88A from DC-89B2 C-89B2 (50 mg: o, o 85 mmof
) to a ≧tonitrile (10mf)? Understand, 1.8
-diazabicyclo(5,4,0)undec-7-nin 1
3.3μ2 was added and stirred at room temperature for 45 minutes. 0.1M
Citrate buffer (p) 14 ) 10 mI! , and extracted with ethyl acetate. After washing with saturated brine and drying over anhydrous sodium sulfate, the solvent was distilled off to obtain crude product 47.
mg was obtained. This was purified by silica gel column chromatography (Wako gel C20010m7!, eluted with chloroform:acetone - 1:0 to 50:1) and DC-88
35.8 mg (yield 83%) of A was obtained.
実施例２ ＤＣ−８９８１からＤＣ−８８Ａの合成り
Ｃ−８９８２の代わりにＤＣ−８９８１（５０ｏ＋ｇ）
を用いるほかは、実施例１と同様にして、ＤＣ−８８Ａ
３２．２ｍｇ（収率７５％）を得た。Example 2 Synthesis of DC-88A from DC-8981 DC-8981 (50o+g) instead of C-8982
DC-88A
32.2 mg (yield 75%) was obtained.
実施例３ ０Ｃ−８９Ａ２からＤＣ−８８Ａの合成りＣ
−８９Ａ２ （１００ｍｇ）をジメチルスルホキシド１
５ｎ／！にン容解した。１．８−ジアザビシクロ（５，
４，０）ウンデカ−７−エン２９μｌを加え室温で１時
間４０分撹拌した。ｐＨ４のクエン酸緩衝液１５ｍｊ２
を加え、酢酸エチルで２回抽出した。Example 3 Synthesis of DC-88A from 0C-89A2 C
-89A2 (100 mg) in dimethyl sulfoxide
5n/! I understand. 1.8-diazabicyclo(5,
29 μl of 4,0) undec-7-ene was added and stirred at room temperature for 1 hour and 40 minutes. pH 4 citrate buffer 15mj2
was added and extracted twice with ethyl acetate.
抽出層を飽和食塩水で洗浄し、無水硫酸すＩ−ＩＪウム
で乾燥し、溶媒を留去した。残渣をシリカゲルカラムク
ロマトグラフィー（ワコーゲルＣ−Ｃ−２Ｏ０２０クロ
ロホルム：アセトン＝に〇〜５０：１で溶出）を用いて
精製し、ＤＣ−８８Ａ３８．５ｍｇ（収率４１％）を得
た。The extracted layer was washed with saturated brine, dried over anhydrous sulfuric acid, and the solvent was distilled off. The residue was purified using silica gel column chromatography (Wako gel C-C-2O020 eluted with chloroform:acetone=0 to 50:1) to obtain 38.5 mg of DC-88A (41% yield).
２ユ曵泣果
本発明により、抗菌剤及び抗腫瘍剤として有用なりＣ−
８８Ａの新規な製造法が提供される。According to the present invention, it is useful as an antibacterial agent and an antitumor agent.C-
A novel method of manufacturing 88A is provided.
Claims (1)
結合の場合ＹはＣＨ＿２ＢｒまたはＣＨ＿２Ｃｌであり
、Ｘが−ＣＨ＿２−の場合ＹはＢｒまたはＣｌである。 ）で表わされる化合物に、塩基あるいは銀塩を反応させ
ることにより、ＤＣ−８８Ａを得ることを特徴とするＤ
Ｃ−８８Ａの製造法。[Claims] General formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, X is a single bond or -CH_2-, and when X is a single bond, Y is CH_2Br or CH_2Cl, and In the case of -CH_2-, Y is Br or Cl. DC-88A is obtained by reacting the compound represented by ) with a base or a silver salt.
Method for manufacturing C-88A.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63265583A JP2553166B2 (en) | 1988-10-21 | 1988-10-21 | DC-88A manufacturing method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63265583A JP2553166B2 (en) | 1988-10-21 | 1988-10-21 | DC-88A manufacturing method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH02115184A true JPH02115184A (en) | 1990-04-27 |
| JP2553166B2 JP2553166B2 (en) | 1996-11-13 |
Family
ID=17419138
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP63265583A Expired - Fee Related JP2553166B2 (en) | 1988-10-21 | 1988-10-21 | DC-88A manufacturing method |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2553166B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5101038A (en) * | 1988-12-28 | 1992-03-31 | Kyowa Hakko Kogyo Co., Ltd. | Novel substance dc 113 and production thereof |
-
1988
- 1988-10-21 JP JP63265583A patent/JP2553166B2/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5101038A (en) * | 1988-12-28 | 1992-03-31 | Kyowa Hakko Kogyo Co., Ltd. | Novel substance dc 113 and production thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2553166B2 (en) | 1996-11-13 |
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