JPH0529039B2 - - Google Patents
Info
- Publication number
- JPH0529039B2 JPH0529039B2 JP60196468A JP19646885A JPH0529039B2 JP H0529039 B2 JPH0529039 B2 JP H0529039B2 JP 60196468 A JP60196468 A JP 60196468A JP 19646885 A JP19646885 A JP 19646885A JP H0529039 B2 JPH0529039 B2 JP H0529039B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- butyloxycarbonyl
- ascamycin
- formula
- reaction
- 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 - Lifetime
Links
- 150000001875 compounds Chemical class 0.000 claims description 11
- LZMCAAGVMFMSKC-UHFFFAOYSA-N Ascamycin Natural products OC1C(O)C(COS(=O)(=O)NC(=O)C(N)C)OC1N1C2=NC(Cl)=NC(N)=C2N=C1 LZMCAAGVMFMSKC-UHFFFAOYSA-N 0.000 claims description 9
- LZMCAAGVMFMSKC-IZKXYQSCSA-N [(2r,3s,4r,5r)-5-(6-amino-2-chloropurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl n-[(2s)-2-aminopropanoyl]sulfamate Chemical compound O[C@@H]1[C@H](O)[C@@H](COS(=O)(=O)NC(=O)[C@@H](N)C)O[C@H]1N1C2=NC(Cl)=NC(N)=C2N=C1 LZMCAAGVMFMSKC-IZKXYQSCSA-N 0.000 claims description 9
- -1 t-butyloxycarbonyl group Chemical group 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 2
- 238000001308 synthesis method Methods 0.000 claims 1
- UVTLTEHAIUJFOX-ZETCQYMHSA-N tert-butyl 1-[(2s)-2-aminopropanoyl]imidazole-2-carboxylate Chemical compound C[C@H](N)C(=O)N1C=CN=C1C(=O)OC(C)(C)C UVTLTEHAIUJFOX-ZETCQYMHSA-N 0.000 claims 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 238000000034 method Methods 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 229930024421 Adenine Natural products 0.000 description 3
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 229960000643 adenine Drugs 0.000 description 3
- 229940126214 compound 3 Drugs 0.000 description 3
- 230000000704 physical effect Effects 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 230000002194 synthesizing effect Effects 0.000 description 3
- BIXYYZIIJIXVFW-UUOKFMHZSA-N (2R,3R,4S,5R)-2-(6-amino-2-chloro-9-purinyl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O BIXYYZIIJIXVFW-UUOKFMHZSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- OVGJPFXCBHGLNH-YFKPBYRVSA-N (2s)-2-[(2-methylpropan-2-yl)oxyamino]propanoic acid Chemical compound OC(=O)[C@H](C)NOC(C)(C)C OVGJPFXCBHGLNH-YFKPBYRVSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- RMFWVOLULURGJI-UHFFFAOYSA-N 2,6-dichloro-7h-purine Chemical compound ClC1=NC(Cl)=C2NC=NC2=N1 RMFWVOLULURGJI-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- APQHKWPGGHMYKJ-UHFFFAOYSA-N Tributyltin oxide Chemical compound CCCC[Sn](CCCC)(CCCC)O[Sn](CCCC)(CCCC)CCCC APQHKWPGGHMYKJ-UHFFFAOYSA-N 0.000 description 1
- IHNHAHWGVLXCCI-FDYHWXHSSA-N [(2r,3r,4r,5s)-3,4,5-triacetyloxyoxolan-2-yl]methyl acetate Chemical compound CC(=O)OC[C@H]1O[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@@H]1OC(C)=O IHNHAHWGVLXCCI-FDYHWXHSSA-N 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000005037 alkyl phenyl group Chemical group 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000003945 anionic surfactant Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 244000000005 bacterial plant pathogen Species 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 description 1
- OVEHNNQXLPJPPL-UHFFFAOYSA-N lithium;n-propan-2-ylpropan-2-amine Chemical compound [Li].CC(C)NC(C)C OVEHNNQXLPJPPL-UHFFFAOYSA-N 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- QAHVHSLSRLSVGS-UHFFFAOYSA-N sulfamoyl chloride Chemical compound NS(Cl)(=O)=O QAHVHSLSRLSVGS-UHFFFAOYSA-N 0.000 description 1
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Description
（技術分野）
本発明は、抗生物質アスカマイシン
（Ascamycin）の合成法に関する。
（発明の背景）
本発明者らは、先に植物に病原菌、特に、キサ
ントモナス（Xanthomonas）属の細菌に対して
抗菌作用を示すアスカマイシンを、ストレプトマ
イセス（Streptomyces）属に属する一菌株
（Streptomyces sp.No.80−Ｈ−647）より分離採
取することに成功した（特開昭59−198981号公報
参照）。そして、アスカマイシンは、下記の構造
式を有することが確認された〔ザ・ジヤーナル・
オブ・アンチバイオテツクス（The Journal of
Antibiotics）vol.37、No.６、pp670−672、（1984
年６月）参照〕。
そこで、本発明者らは、アスカマイシンの合成
法を確立し、各種アミノ酸アナログの構造とその
活性相関関係を明らかにすることを目的として、
更に研究を続けた結果、その過程において本発明
を完成したものである。
（発明の目的）
本発明の目的は、アスカマイシンの合成法を提
供することにある。
（発明の構成）
本発明の出発物質は、２−クロロ−９−（2′，
3′−Ｏ−イソプロピリデン−5′−Ｏ−スルフアモ
イル−β−Ｄ−リボフラノシル）アデニン(2)であ
り、例えば次の方法により得ることができる。す
なわち、２，６−ジクロロプリン(A)とβ−Ｄ−リ
ボフラノース−１，２，３，５−テトラアセテー
ト(B)から２段階で２−クロロアデノシン(C)を得る
（モンゴメリー（Montgomery）、J.A.ヒユウソン
（Hewson）、K.（1964）、ジヤーナル・オブ・ヘテ
ロサイクリツク・ケミストリー（J.Heterocycle.
Chem.）、１、213−214参照）。得られた２−クロ
ロアデノシン(C)を2′，3′−イソプロピリデンアセ
タール体(D)とし、次いで、水素化ナトリウム存在
下、スルフアモイルクロリドを作用させ、出発物
質２を得る（グウ（Gough）、J.C.，ペングリス
−カレデス（Penglis−Caredes），F.，マグイレ
（Maguire），M.H.（1978）ジヤーナル・オブ・メ
デイカル・ケミストリー（J.Med.Chem.）、21、
520−525参照。）
以上の工程を示せば、次のとおりである。
得られた出発物質２を、次の工程により処理し
て、目的のアスカマイシン１を得ることができ
る。
すなわち、化合物２を、重炭酸ジ−ｔ−ブチル
（di−ｔ−butyl dicarbonate）と反応させて、
N6−ｔ−ブチルオキシカルボニル体３を得る。
この反応は、NaH、トリメチルシリルクロリド、
ｎ−ブチルリチウム、リチウムジイソプロピルア
ミン、ビス（トリ−ｎ−ブチルスズ）オキサイド
等の存在下で行うことができる。溶媒としては、
ジメチルホルムアミド、ジオキサン、テトラヒド
ロフラン、ベンゼン等を用いることができる。
反応温度、反応時間は、それぞれ、−78〜100
℃、１〜20時間が適当である。
次いで、得られたN6−ｔ−ブチルオキシカル
ボニル体３を、ｔ−ブチルオキシカルボニル−Ｌ
−アラニルイミダゾール（ｔ−
butyloxycarbonyl−Ｌ−alanylimidazole）とカ
ツプリング反応させて、化合物４を得る。
この反応は、前段の反応（ｔ−ブチルオキシカ
ルボニル化）と同様の条件で反応を行うことがで
きる。
得られた化合物４を、脱保護（脱イソプロピリ
デン及び脱ｔ−ブチルオキシカルボニル）を行つ
て、目的のアスカマイシン１を得る。この反応
は、トリフルオロ酢酸、トリフルオロメタンスル
ホン酸、メタンスルホン酸、HF、HBr／酢酸、
HCl／酢酸、HCOOH、酢酸又はこれらの酸等と
水との混合液を用いて行うことができる。
反応温度、反応時間は、それぞれ、−78〜100
℃、0.5〜20時間が適当である。
以上の工程を示せば、次のとおりである。
以下、本発明を実施例により更に詳しく説明す
るが、本発明はこれらに何ら限定されるものでは
ない。
実施例 １
N6−ｔ−ブチルオキシカルボニル−２−クロ
ロ−９−（2′，3′−Ｏ−イソプロピリデン−5′−Ｏ
−スルフアモイル−β−Ｄ−リボフラノシル）ア
デニン３
化合物236mg（0.0857mmole）を無水DMF0.72
mlに溶解し、無水DMF0.5mlに懸濁した水素化ナ
トリウム（55％）20.6mgに−20℃にて滴下した。
室温にて30分間撹拌し、再び−20℃に冷却し、
無水DMF0.5mlに溶解したジ−ｔ−ブチルオキシ
−ジカーボネート21.6μを滴下した。−20℃から
徐々に０℃まで２時間かけて温度を上昇させた。
反応液に酢酸エチルを加え、10％クエン酸、飽和
食塩水にて順次洗浄し、無水硫酸ナトリウムにて
乾燥し、減圧濃縮して、シリカゲルTLCを用い
て精製し、化合物38.1mg（収率80％）を得た。
〔化合物３の物理的性質〕
質量分析（SIMS）：ｍ／ｚ 521（MH）+ 1
H−NMR：δCDC l3 TMS8.12（1H，Ｓ， C8−Ｈ）
6.17（1H，ｄ，Ｊ＝３Hz，C1′−Ｈ）
5.31（1H，dd，Ｊ＝３Hz，Ｊ＝6.7Hz，C2′−Ｈ）
5.07（1H，dd，Ｊ＝４Hz，Ｊ＝6.7Hz，C3′−Ｈ）
4.57（1H，ｍ，C4′−Ｈ）
4.39（2H，ｍ，C5′−Ｈ）
UV：λnax（MeOH） 255（11000sh）
273（18200 ）
280（16100sh）
実施例 ２
N6−ｔ−ブチルオキシカルボニル−２−クロ
ロ−９−〔5′−Ｏ−（Ｎ−ｔ−ブチルオキシカルボ
ニル−Ｌ−アラニル）スルフアモイル−β−Ｄ−
リボフラノシル〕アデニン４
化合物337mg（0.0667mmole）を無水DMF0.72
mlに溶解し、無水DMF0.5mlに懸濁した水素化ナ
トリウム（55％）5.8mgに−20℃で加えた。室温
で10分間、−20℃で20分間撹拌した。反応液に、
ｔ−ブチルオキシアラニン15mg及びＮ，N′−カ
ルボニルジイミダゾール13mgを無水DMFに溶解
し、室温で30分間反応させた溶液を−20℃で滴下
した。−20℃から室温まで６時間かけて徐々に温
度を上昇させながら反応させた。反応液に酢酸エ
チルを加え、10％クエン酸、飽和食塩水にて順次
洗浄し、無水硫酸ナトリウムにて乾燥し、減圧濃
縮して、シリカゲルTLCを用いて精製し、化合
物438mg（収率86％）を得た。
〔化合物４の物理的性質〕
m.p.：152〜160℃（分解）
質量分析（SIMS）：ｍ／ｚ 714（Ｍ＋Na）+ 1
H−NMR：δCDC l3 TMS8.54（1H，Ｓ， C8−Ｈ）
6.31（1H，ｄ，Ｊ＝３Hz，C1′−Ｈ）
5.28（1H，dd，Ｊ＝３Hz，Ｊ＝6.3Hz，C2′−Ｈ）
5.05（1H，dd，Ｊ＝２Hz，Ｊ＝6.3Hz，C3′−Ｈ）
4.57（1H，ｍ，C4′−Ｈ）
4.33，4.23（2H，各dd，C5′−Ｈ）
4.0（1H，ｍ，
TECHNICAL FIELD The present invention relates to a method for synthesizing the antibiotic ascamycin. (Background of the Invention) The present inventors previously discovered that ascamycin, which has an antibacterial effect against plant pathogenic bacteria, particularly bacteria of the genus sp. No. 80-H-647) (see JP-A-59-198981). Ascamycin was confirmed to have the following structural formula [The Journal
The Journal of Antibiotics
Antibiotics) vol.37, No.6, pp670-672, (1984
(June)). Therefore, the present inventors established a method for synthesizing ascamycin and clarified the structures of various amino acid analogs and their activity relationships.
As a result of further research, the present invention was completed in the process. (Object of the invention) An object of the present invention is to provide a method for synthesizing ascamycin. (Structure of the Invention) The starting material of the present invention is 2-chloro-9-(2',
3'-O-isopropylidene-5'-O-sulfamoyl-β-D-ribofuranosyl)adenine (2), which can be obtained, for example, by the following method. That is, 2-chloroadenosine (C) is obtained in two steps from 2,6-dichloropurine (A) and β-D-ribofuranose-1,2,3,5-tetraacetate (B) (Montgomery). , J.A. Hewson, K. (1964), Journal of Heterocyclic Chemistry (J.Heterocycle.
Chem.), 1 , 213-214). The obtained 2-chloroadenosine (C) is converted into a 2',3'-isopropylidene acetal (D), and then treated with sulfamoyl chloride in the presence of sodium hydride to obtain starting material 2 (Gu( Gough, JC, Penglis-Caredes, F., Maguire, MH (1978) Journal of Medical Chemistry (J.Med.Chem.), 21 .
See 520-525. ) The above process is as follows. The obtained starting material 2 can be processed through the following steps to obtain the desired ascamycin 1. That is, by reacting compound 2 with di-t-butyl dicarbonate,
N 6 -t-butyloxycarbonyl compound 3 is obtained.
This reaction involves NaH, trimethylsilyl chloride,
It can be carried out in the presence of n-butyllithium, lithium diisopropylamine, bis(tri-n-butyltin) oxide, or the like. As a solvent,
Dimethylformamide, dioxane, tetrahydrofuran, benzene, etc. can be used. The reaction temperature and reaction time are −78 to 100, respectively.
°C for 1 to 20 hours is appropriate. Next, the obtained N 6 -t-butyloxycarbonyl compound 3 was converted into t-butyloxycarbonyl-L
-alanylimidazole (t-
butyloxycarbonyl-L-alanylimidazole) to obtain compound 4. This reaction can be carried out under the same conditions as the previous reaction (t-butyloxycarbonylation). The obtained compound 4 is deprotected (removal of isopropylidene and t-butyloxycarbonyl) to obtain the target ascamycin 1. This reaction includes trifluoroacetic acid, trifluoromethanesulfonic acid, methanesulfonic acid, HF, HBr/acetic acid,
This can be carried out using HCl/acetic acid, HCOOH, acetic acid, or a mixture of these acids and water. The reaction temperature and reaction time are −78 to 100, respectively.
°C for 0.5 to 20 hours is appropriate. The above steps are as follows. EXAMPLES Hereinafter, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited thereto. Example 1 N 6 -t-butyloxycarbonyl-2-chloro-9-(2',3'-O-isopropylidene-5'-O
-Sulfamoyl-β-D-ribofuranosyl)adenine 3 Compound 236 mg (0.0857 mmole) was added to anhydrous DMF 0.72
ml and added dropwise to 20.6 mg of sodium hydride (55%) suspended in 0.5 ml of anhydrous DMF at -20°C. Stir at room temperature for 30 minutes, cool again to -20°C,
21.6μ of di-t-butyloxy-dicarbonate dissolved in 0.5ml of anhydrous DMF were added dropwise. The temperature was gradually raised from -20°C to 0°C over 2 hours.
Ethyl acetate was added to the reaction solution, washed sequentially with 10% citric acid and saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified using silica gel TLC to obtain a compound of 38.1 mg (yield: 80 %) was obtained. [Physical properties of compound 3] Mass spectrometry (SIMS): m / z 521 (MH) + 1 H-NMR: δ CDC l3 TMS 8.12 (1H, S, C8-H) 6.17 (1H, d, J = 3Hz , C1'-H) 5.31 (1H, dd, J=3Hz, J=6.7Hz, C2'-H) 5.07 (1H, dd, J=4Hz, J=6.7Hz, C3'-H) 4.57 (1H, m, C4'-H) 4.39 (2H, m, C5'-H) UV: λ nax (MeOH) 255 (11000sh) 273 (18200 ) 280 (16100sh) Example 2 N 6 -t-butyloxycarbonyl-2 -Chloro-9-[5'-O-(N-t-butyloxycarbonyl-L-alanyl)sulfamoyl-β-D-
Ribofuranosyl]adenine 4 Compound 337mg (0.0667mmole) in anhydrous DMF 0.72
ml and added at -20°C to 5.8 mg of sodium hydride (55%) suspended in 0.5 ml of anhydrous DMF. Stirred at room temperature for 10 minutes and at -20°C for 20 minutes. In the reaction solution,
A solution in which 15 mg of t-butyloxyalanine and 13 mg of N,N'-carbonyldiimidazole were dissolved in anhydrous DMF and reacted at room temperature for 30 minutes was added dropwise at -20°C. The reaction was carried out while gradually increasing the temperature from -20°C to room temperature over 6 hours. Ethyl acetate was added to the reaction solution, washed sequentially with 10% citric acid and saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified using silica gel TLC to obtain 438 mg of the compound (yield 86%). ) was obtained. [Physical properties of compound 4] mp: 152-160℃ (decomposition) Mass spectrometry (SIMS): m / z 714 (M+Na) + 1 H-NMR: δ CDC l3 TMS 8.54 (1H, S, C8-H) 6.31 (1H, d, J=3Hz, C1'-H) 5.28 (1H, dd, J=3Hz, J=6.3Hz, C2'-H) 5.05 (1H, dd, J=2Hz, J=6.3Hz, C3'-H) 4.57 (1H, m, C4'-H) 4.33, 4.23 (2H, each dd, C5'-H) 4.0 (1H, m,
〔α〕20 D＋2.34°（Ｃ＝１、H2O）
UVスペクトル：νnax 263nm（ε12270）1
H−NMRスペクトル：δD 2 O
1.27，ｄ，Ｊ＝7.0Hz，（−CH3）．
3.65，ｑ（
[α] 20 D +2.34° (C=1, H 2 O) UV spectrum: ν nax 263 nm (ε12270) 1 H-NMR spectrum: δ D 2 O
1.27, d, J=7.0Hz, (-CH 3 ). 3.65, q(
【式】）13 C−NMRスペクトル：δD2O 17.380（−CH3）， 52.206（[Formula]) 13 C-NMR spectrum: δ D2O 17.380 (-CH 3 ), 52.206 (
【式】），
177.226（Ｃ＝０）
以上の性質及び高速液体クロマトグラフイーに
おける保持時間は、標品のアスカマイシンと一致
した。[Formula]), 177.226 (C=0) The above properties and retention time in high performance liquid chromatography were consistent with standard ascamycin.
１ 一般式ROSO3M（式中Ｒは炭素数６〜22のア
ルキル基又はアルキルフエニル基であり、Ｍは窒
素原子を少なくとも１個以上有する陽イオンであ
る）で示されるアニオン性界面活性剤の共存下、
15℃以下でゲル電気泳動を行うことを特徴とする
生体膜蛋白質の分離精製法。
1 Anionic surfactant represented by the general formula ROSO 3 M (wherein R is an alkyl group or alkylphenyl group having 6 to 22 carbon atoms, and M is a cation having at least one nitrogen atom) Under the coexistence of
A method for separating and purifying biological membrane proteins, which is characterized by performing gel electrophoresis at 15°C or lower.
Claims (1)
を示す。） で示される化合物を得、該化合物をｔ−ブチルオ
キシカルボニル−Ｌ−アラニルイミダゾールと反
応させて、構造式： （式中、Bocは、前記に同じ。） で示される化合物を得、該化合物を酸で処理する
ことを特徴とする、構造式： で示されるアスカマイシン（Ascamycin）の合
成法。 (In the formula, Boc represents a t-butyloxycarbonyl group.) A compound represented by the formula is obtained, and the compound is reacted with t-butyloxycarbonyl-L-alanylimidazole to give the structural formula: (In the formula, Boc is the same as above.) A structural formula characterized by obtaining a compound represented by the following and treating the compound with an acid: Synthesis method of ascamycin shown in
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60196468A JPS6256500A (en) | 1985-09-05 | 1985-09-05 | Synthesis of ascamycin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60196468A JPS6256500A (en) | 1985-09-05 | 1985-09-05 | Synthesis of ascamycin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6256500A JPS6256500A (en) | 1987-03-12 |
| JPH0529039B2 true JPH0529039B2 (en) | 1993-04-28 |
Family
ID=16358302
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP60196468A Granted JPS6256500A (en) | 1985-09-05 | 1985-09-05 | Synthesis of ascamycin |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6256500A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5824657A (en) * | 1997-03-18 | 1998-10-20 | Cubist Pharmaceuticals, Inc. | Aminoacyl sulfamides for the treatment of hyperproliferative disorders |
-
1985
- 1985-09-05 JP JP60196468A patent/JPS6256500A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6256500A (en) | 1987-03-12 |
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