TW480263B - Epothilones with a modified side chain - Google Patents
Epothilones with a modified side chain Download PDFInfo
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- TW480263B TW480263B TW087102758A TW87102758A TW480263B TW 480263 B TW480263 B TW 480263B TW 087102758 A TW087102758 A TW 087102758A TW 87102758 A TW87102758 A TW 87102758A TW 480263 B TW480263 B TW 480263B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
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- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Plural Heterocyclic Compounds (AREA)
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- Other Resins Obtained By Reactions Not Involving Carbon-To-Carbon Unsaturated Bonds (AREA)
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Description
480263 A7 Β7 五、發明説明( 裒氣塞坐_ A及B為習知;參見例如專利Dp 4 138 042 及 PCT/EP 96/05 080。 本發明係有關-種在16,17位置上修飾之環氧嗟賴 的製備法,其以3,7-被保護或未被保護之環氧酮 B為基礎, ⑻八汉 a) 將其在16,17雙鍵氫化或 b) 在16,17雙鍵加上_素或 C)雙鍵環氧化,必要時並將得到的環氧化物還原 此發明方法之特徵為: -採方法⑷時,以二亞胺或氫及—非均 劑進行氫化, --勻金屬催化 -採方法⑷時,以—過氧酸n氧乙燒進行環 此外,本發明尚有關一種環氧噻唑。 備法,其使3,7-被護或未被護環氧嗔唾_ A或 勿之製 法轉變為N-氧化物,必要時並使得到的⑽二習知方 烷基化,而得到一 〇_烷基化產物。 進行0- 經濟部中央標準局員工消費合作社印製 此發明方法之特徵為:以過氧酸 N-氧化,並以親電子烧基、芳基氧乙燒進行 基块或三甲基氧鏽四氟魏鹽進行偶 ^尤其是甲 f發明方法之特徵尚為:使得到之 Katada反應,尤其是依據H〇uben_w 物進行一 頁。 弟E7b冊,第646 本紙張尺度適财® _轉(CNSU^^ ( 210Χ 297.^Γ)-〜—_ Α-87078 "〜一 480263 A7 B7 五、發明説明(2 ) 此發明方法之特徵尚為:以一活化碳酸衍生物,尤其 是破酸酐或碳酸氯化物,進行Katada反應。 此發明方法之特徵尚為:以醋酸酐進行Katada反應, 必要時並將得到的21-乙醯氧基環氧噻唑酮以習知方法分 裂成21-經基-環氧喧唾_八或8 (環氧喧峻酮E或F)。 此發明方法之特徵尚為:以水解或酶催化方式進行偶 發分裂。 本發明尚有關一種在C19位置上修飾之環氧噻唑酮的 製備法,其將3,7-被保護或未被保護之環氧噻唑酮A或B 在C19位置上金屬化,並依習知方法以親電子試劑攻擊在 C19位置上修飾之烷基、芳基、雜芳基、鹵素、氧或硫取 代環氧噻唑酮。 此發明方法之特徵為:以丁基鋰金屬化。 本發明尚有關一種在C27位置上修飾之環氧噻唑酮的 製備法,其使烯丙基團(C17,C16及C27)依習知方法在C27-甲基團被一雜原子取代。 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 此發明方法之特徵為:C27甲基團被一溴原子取代, 尤其是藉助N-溴琥珀醯亞胺,必要時並將得到的溴化物轉 變為一 C27·甲基-化合物。 最後,本發明尚有關以本發明方法製備出之化合物。 實例1 :二環氧環氧σ塞唾酮A(la) 使環氧噻唑酮A (5毫克,10微莫耳)溶於丙酮(1毫升) -4- 本紙張尺度適用中國國家標準(CNS ) A4規枱(210X297公釐) 480263 經濟部中央標準局員工消費合作社印製 kl B7 五、發明説明() 3 的溶液在0°c下與二曱基二環氧乙烷(0.4毫升,28微莫 耳’ 0.07M,溶於丙酮)混合,於數小時内將溫度升高至 室溫’並在此溫度下攪拌2〇小時。由於薄層色層分離後 尚存在離析物,故再加入二曱基二環氧乙烷(0·25毫升, 17微莫耳),在室溫下重新攪拌反應混合物20小時。除去 溶劑,並以 PSC( 0·25 X 200 X 200 毫米,10% MeOH:CH2Cl2) 洗務殘渣。分離出: L 1·4毫克(27%)二環氧環氧噻唑酮a (3:2差向混合物 在 C16-C17)。Rf: 0.63(10% MeOH·· CH2C12); Rf: 6·79(同 分異構物1)及7·39 (同分異構物2)分鐘(RP 18, 250 x4 毫米’ MeOH:H2〇 65:35,1 毫升/分鐘); 1Λ (Λΐ/2) " 510 (^ί1 H-NMR (400 Μ92. CDC1 , Η"26λ 147 66 iW4)fr.〇8 (¾ 3H, H-23), ‘ H 1 产Ϊ;(同分異構抑 8 寅 6,98 (¾ 1H> H‘19)· 5·11 (机卜"·7 及 2 5 it m 1Ηβ tH7)( 3,06 (qd4J-6.6 ^ 2Λ 23). ^ 36( ? 3Π,H 22)' hlS W%,/ac6,6 H2a 3H*H-24)*lil4 (s· m> Hm26)^107 ^ 3H> H· 2· 〇·8毫克(16%)環氧噻唑酮a。N-氧化物,Rf ·· 0·44(10%
MeOH: CH2C12) ; Rf ·· 4 25 分鐘(Rp 18, 25〇 χ 4 毫米, MeOH:H20 65:35,1 毫升/分鐘);MS:(m/z)=510(M+);咕 NMR:見方法1 實例2 :二氫環氧噻唑酮A(lc) 將存在活性碳(5毫克,1〇0/〇)中的鈀加入溶於乙醇(2毫 升)的壤氧嗔嗤_ A ( U毫克,22微莫耳)溶液中,並將 -5- 本紙張尺度適财關家縣(CNsT^Tf^^Fy * 衣 (請先閱讀背面之注意事項再填寫本頁)
、tT 480263 A7 B7 五、發明説明( 此黑色懸浮體在室溫下暴露於一 H2環境24小時。由於反 應在薄層色層分離後尚未完成,故再加入一份pd/C,並在 一 H2環境下繼續攪拌20小時。產物的分離使用PSC (1 X 200 \ 200 毫米,1〇〇/〇1^0比(:1120:12)。分離出: 1· 0.5 毫克(5%)二氫環氧噻唑酮 A。Rf: 0.60 (10% MeOH: CH2C12); Rf: 10.80 分鐘(RP 18, 250 X 4 毫米,Me0H:H20 65:35,1 毫升 /分鐘);MS:(m/z)=496(M+); 478,408, SOS^H-NMRGOO MHz,CDC13,選擇信號) 山":卜7.05(<^=661^出,〇取6‘77(心机叫外 iddd J-/1 4,42 1& 3 0 Hz, ih, li-3)f 3.70 1 hV hSd /¾¾ » 3Λ Hz, JH; II-6), 3.07 (d,J= 12.7 Hzf H 2.0 Hz, 1H,H.13),Z91 (ddd, J=9,7, 3.6 ^ 2.6 Hz, IH 5 Ι7κ\2ί^^3^^ J-<,,3·7 ^UJ Πζ·1H* 2 24 i2 7 6 31il IM4 # 09 3Hf 1 W3),a"7,1 3H> H-25), 0 93 Wf 2· 8毫克(72%) 15-脫氧-二氳環氧噻唑酮酸。Rf : 0.10 (10% MeOH: CH2C12) 〇 實例3 : 16-羥基環氧噻唑酮A(lb) 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 將存在活性碳(10毫克,10%)中的鈀加入溶於乙醇(2 毫升)的二環氧環氧噻唑酮A (7毫克,14微莫耳,1:1 差向混合物在C-16)溶液中,並將此黑色懸浮體在室溫下 暴露於一 H2環境24小時。由於反應在薄層色_層分攀後尚 未完成,故再加入一份Pd/C,並在一 H2環境下繼續攪拌80 小時。產物的分離使用PSC (1 X 200 X 200毫米,10% MeOH: 本紙張尺度適用中國國家標準(CNS ) A4規格(210X 297公釐) 480263 A7 B7 五、發明説明( CH2C12)。分離出: 1. 3毫克(43%) 16-羥基環氧噻唑酮A (同分異構物1)。 Rf: 0.38 (10% MeOH: CH2C12); Rf : 6.65 分鐘(RP 18, 250 X 4 毫米,MeOH.H20 65:35,1 毫升/分鐘)"H-NMR^OO MHz, CDC13,選擇信號)
(dbr ^ !0.5 IK h' ul ^ JI5V1Η, Η-Ι2), 2J3 (d, 14,3 Hz, 1Η, I^I7h)f 2.68 (¾ 3Η. 11^211 2.63 (dd 7- 16 6 ^ fu ?·3 Ηζ* ^ έ 2· 3毫克(43°/〇)16-羥基環氧噻唑酮Α (同分異構物2)。Rf : 0.31 (10%MeOH: CH2C12) ; Rf ·· 6.10 分鐘(RP 18, 250 x 4 毫米,MeOH:H20 65:35,1 毫升/分鐘)"H-NMRPOOMHz, CDC13,選擇信號) ί« = 05 (s, 1H, H-19), 5.02 (dd, J = 11.? und 2.0 Hz, UIf II-15), 4.38 (dbr,·; = U,2 Hz, Π-3)·3·67 (dd,·/作 4 及 3 取 1H· 1如分· 3,M (q山 6·8 及 3.0 1Hf H-6)t 2.95 (d, 15.3 IH, H-17a)f 2,89 (d, J= 15.3 11¾ m, H^7b), 2M (ddd, ./^ ΐρ,3·6 及 2·0Η々 1H去Η·13),2,81 (ddd,J=9.7,3.6 及 2.5H& m*H-⑵·2,70(3·3Η·Η-2子),2.53(机·/® i5.8 及 Π·7Π^1Η·Η-2β),2·14(ω,>15·8 及 2.0取 lH,H-2b>,2.08 (dW 二 14·3 及 2·0 Ηζ» 1Η· H-14«), U9 (ϋ· 3Η· Η·22), U5 (8, 3H, Η·26), U9 (<J· ·/成 6·6 ifa; 3Η,Η·24), 1·〇5 (ι 3Η, Η·23), 0·99 ((!,·/= λΐ 取 3Η· Η·25)· 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁} 環氧噻唑酮Α-Ν-氧化物(2a):將溶於〇·5毫升二氯甲烷的 100毫克70% m-氯過苯酸加入溶於1毫升二氣甲烷的100 * 毫克環氧噻唑酮A中。在室溫下攪拌6小時後,以二氯曱 烧稀釋,並先後以亞硫酸納溶液(以破壞過剩之過酸)及 本紙張尺度適用中國國家標準(CNS ) A4規格(210X 297公釐) 經濟部中央標準局員工消費合作社印聚 480263 ,. A7 B7 五、發明説明(6) 碳酸鈉溶液搖動。真空蒸發掉溶劑,使用一 Nucleosil RP-18分離管(250 X 20毫米,洗提液甲醇/水60:40)以製備 HPLC法分離殘渣。產物為60毫克無色的油。
Rf= 0.60 (矽膠薄層色層分離鋁箔,洗提液二氯曱烷/甲醇 9:1) ; ESI-MS (負離子)m/z510; UV (甲醇):lamda max· 240 nm; IJC-NMR (CDClj): C-l 170,5, C-2 39.9, C-3 70.8, C-4 55.1, C-5 221.4, C^6 40,9, C-7
72.9· C-8 37,6· 31.8, (Mil 22,8· CM1 28.0, CM2 58A (M3 55,8· C-14 32,2, CMS 75:5· C-16 144.5, C-17 UL4· C-18 143,4, C-19 U0Jf C-20 丨45.6· C-21 13 5,’ C-22 15·4· C,23 23.3, C-24 12.0, C_25 16.5, C-27 18,2 ppm; < CDCl:i): 2α·Η 2‘12 dd, 2WI 2·47 d4 3,H 4·55 dd, 3-OH 6.48 寬· 6·« 3.25 dqt 7-H 3.72 ddf 8-H 1,81 m, 9a-H 1.34 n\ 9b-H 1.56 m, 10-¾ L48 m, 1 la^H 1 27 m, 1 lb-ΙΪ i.87 m, 12^H 2,92 ddd, 13-Π 2.98 m, 14a-II 1.67 dddf I4h-H 2,23 d# 15-H 5,33 d· 17-H6.82$, i94ir〇〇a,2^H32.6! s,22^H, K02sf23-H, 1.42^24-H, U8d* 25-Hj 〇;99 d, 27-H3 2,04 s pptn, 21-乙醯氧基環氧嗜嗤_ A( = 21-乙酿基環氧鳴唾_ E)(3a): 將0.05毫升2,6-二_第三丁基吡啶及〇.1毫升醋酸酐加入溶 於0.5毫升二氣甲烷的50毫克環氧噻唑酮Α-Ν-氧化物(2a) 中。以15分鐘加熱至75°C後,真空蒸發掉溶劑及試劑, 並使用一 Nucleosil RP-18分離管(250 X 20毫米,洗提液 曱醇/水60:40)以製備性HPLC法分離殘渣。產物為30毫 克無色的油。
Rf = 0·50 (石夕膠薄層色層分離|呂箔,洗提液二氯甲烧/甲醇 95:5); ESI-MS (負離子)m/Z 552; UV (甲醇):lamda max· 210, 250 nm; ):糾则,丨 本蜱張尺度適用中國國家標準(CNS ) Α4規格(210Χ 297公楚) Γ I 衣 (請先閱讀背面之注意事項再填寫本頁)
、1T 480263 A7 經濟部中央標準局員工消費合作社印製 五、發明説明( 環氧喧°坐_ E(3b):將一滴濃縮氨水加入溶於毫升甲醇 的10宅克21-乙醯氧基環氧喧。坐酮a (3a)中,加熱1小時 使達40°C,並真空蒸發成乾燥物。以製備性薄層色層分離 法分離殘渣。產物6毫克,與環氧噻唑酮E樣品一致。 實例4: 19-甲基環氧噻唑酮A(4b) 使溶於THF (1毫升)的環氧噻唑酮A(15毫克,3〇微莫 耳)在-90°C下與正丁基鋰(100微升,16〇微莫耳,16M 溶於己烷)混合。溶液立即變為金橙色。在_9〇〇c下攪拌i5 分鐘後,使該反應溶液與甲基碘(1〇〇微升,16毫莫耳) 混合。將得到之淡黃綠色溶液加熱至〇〇〇c,並以pH=7 〇 之緩衝劑(2毫升)驟冷。以〇1 N鹽酸將乳膠調整至pH6。 固體NaCl飽和後,以CH/L (2χ5毫升)及乙酸乙酯(5 毫升)提取水相,以MgS04乾燥結合之有機相、過濾,並 以 Rotavap 除去溶劑。以 PSC( ! χ 2〇〇 χ 2〇〇 毫米,j〇% Me〇H: CH2C12)及 HPLC ( RP 18, 250 X 16 毫米,Me0H:H20 65:35 ) 進行淨化。分離出: 1_ 2.5 毫克(17。/。)19-甲基環氧噻唑酮 Ac)Rf:〇.5〇 (1〇% Me〇H: CH2Cl2);Rf: 11.70 分鐘 65:35,1 毫升/分鐘);MS: (m/z) = 5〇8(M+),42〇, 32〇;lH_ NMR(300 MHz,CDC13 ’ 選擇信號) 31)1,2·15 (鐵 > 15山 Wl J 6.8 Hz, 3Π, H-24), U0<a# 3H| H-23)f !.〇〇(d, J-6.8 Ife 3H? H-25). 2·約50%環氧嗜唾嗣a 9- 本紙張尺度適用中國國家標準(CNS ) A4規格( „ . ^^衣-- (請先閲讀背面之注意事項再填寫本頁) 、1Τ 480263 Μ B7 五、發明説明( 貫例5 : 19-溴環氧噻唑酮A(4a) (請先閱讀背面之注意事項再填寫本頁) 使溶於THF (2.5毫升)的環氧噻唑酮A (25毫克,5〇微 莫耳)在-90°C下與正丁基鋰(160微升,225微莫耳,:L6M 溶於己烷)混合。溶液立即變為金橙色。在-9(rc下攪拌i5 分鐘後,加入溶於THF (0‘5毫升)的溴琥珀醯亞胺(27 毫克,150微莫耳)。溶液緩慢變色。將得到之淡棕色反應 混合物加熱至-30°C,並以0.1 N鹽酸(1毫升)調整至 6·5。固體NaCl飽和後,以CH2C12 (2x5毫升)及乙酸乙 酯(5毫升)提取水相,以MgS〇4乾燥結合之有機相、過 濾,並以Rotavap除去溶劑。以PSC ( 1 χ200 χ 200毫米, 10% MeOH: CH2C12)及 HPLC (RP 18, 250 X 16 毫米,
MeOH:H20 65:35)進行淨化。分離出: 1· 2.6 毫克(9%) 19-溴環氧噻唑酮 AcRf: 0.53 (10%MeOH: CH2C12); Rf : 20.78 分鐘(RP 18, 250 X 4 毫米,MeOH:H20 65:35,1 毫升/分鐘);MS:(m/z) = 574 及 572(M+),556,554, 468, 466, 386, 384, SW/H-NMRPOO MHz,CDC13,選擇信 號) , :6-6,43 經濟部中央標準局員工消費合作社印製 5,46(每>8;7 及 2,3取出,办15),4.13(蛾7資9.4§6,0 及 3.8HzJIUW),3.80<dd· J = 8 ^ 4 Hz, IH, H-7), 3.38 (d, J= 6\0 Hz, 1H, OH), 3.22 (qd,,/* 6.8 S 5.3 1Hf 6), 3.05 (电 / ” 8,3 及 1H, H-U), 2·91 (dt* _ 7·5 及 3.7 Ήζ· 1H· ΪW2),2.66 (ef 3H,H,2l),2.55 (dd,·;叫4/7 及 9·4 电 1H· Η·2ι>, 2·47 (dd,·/- 14.7 及 3·8 Hz^ 1H, H*2b), 2A6(d,J^ U Hz, 3^^26),2,14(4^^-= 14.7 S: 3.8 Hz, IH, Η-Ι4»), 1.90((1^./- IJ S 8.3 Hz, 1H, H-14h), \M (¾ 3H, H-22), L17 (d,J- 6,« Hz, 3H, H^4), 1J1 (η3 3H, H-23), 1·01 (d, 6;8 Hz, 3H, H-23).
2·約60%環氧噻唑酮A -10- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X 297公釐) 480263 -—- A7 B7 五、發明説明,(9 ) 合成實例la至5a
(請先閲讀背面之注意事項再填寫本頁) 10 R1,RS,Η· ΧΫ · -Ο-』β 二 Η b ArKfiM3« R1,Ra ϋ X · OH Υ 麵 Η , R · Η ο n:mz〇A3t R\R2 - Hf X - Η Υ · Η , β Η
2a R-亂料 R1, R2 Η, Ζ CT; R,Β b 寒=e«3, R1,ft2,Η, Ζ - OCH3 BFr} R ^ H 本:紙張尺度適用中國國家標準(CNS ) Α4規格(210X 297公釐)
、1T 經濟部中央標準局員工消費合作社印製 480263 kl B7 五、發明説明(10 ) R RaOCH2
乙醯基 3ά 貢:·取· R\ R2 - Hf Ra - AOdtyl r Η b R=3r3CK8f R1, RVR3 - Η Λ ^ Η
R
4« Pt=eC*af R\ R8 - Hf V - Br 4 纪 h *;V - CH9. R1,R2 H # (¾ ^ μ
本紙張尺度適用中國國家標準(CNS ) A4規格(210X 297公釐) (請先閱讀背面之注意事項再填寫本頁)
Claims (1)
- 480263 J·» A8 B8 C8 D8 六 申請專利範圍 專利申請案第87102758號 ROC Patent Appln. No.87102758 修正之申請專利範圍中文本-附件(二) Amended Claims in Chinese - Enel. Π (民國90年6月丨丨日送呈) (Submitted on June f |,2001) ^種製備16,17位置上經修飾之環氧噻唑酮之方法,其 以3,7_未被保護之環氧噻唑酮a及B為起始物質 〇(請先閱讀背面之注意事項再填寫本頁) 2. 經濟部智慧財產局員工消費合作社印製 4. _ 環氧噻唑酮A 環氧噻唑酮B a) 將其在16,17雙鍵氫化或 b) 在16,17雙鍵環氧化,必要時並將得到的環氧化物 遥原成16-醇。 根據申請專利範圍第1項之方法,其中 一採方法(a)時,以二亞胺或氫及鈀/活性碳催化劑進 行氫化, -採方法(b)時,以一過氧酸或一二環氧乙烷進行環氧 化。 2,3—未飽和環氧噻唑酮-N-氧化物之製備法,其使 在2,3位置上具一雙鍵的7-未被保護之環氧嗔。坐酮a 或B以習知方法轉變為一沁氧化物。 種製備環氧噻唑酮-N-氧化物之方法,其使3,7·未被 13 (210 X 297 公釐) ^ΕΝυ:87078 裝--------訂-------- A8 B8 C8 D8申請專利範圍 保護之環氧噻唑酮A或B轉變為N-氧化物,其中以過 氧酸或一環氧乙烧進行N-氧化。 根據申請專利範圍第3項或第4項之方法,其中使得 到之N-氧化物進行一 Katada反應,尤其是依據 Houben-Weyl,第 E7b 冊,第 646 頁。 根據申請專利範圍第5項之方法,其中以一活'化碳酸 衍生物,尤其是碳酸酐或碳酸氣化物,進行Katada反 應。 根據申請專利範圍第6項之方法,筹中以醋酸軒進行 Katada反應,必要時並將得到的21•乙磕氧基環氧噻唑 酮以白知方法分裂成21-羥基-環氧噻唑酮A或B (環 氧口塞嗤酮E或F)。 : ^ 根據申請專利範圍第7項之方法,其中可選的分裂係 以水解或酶催化方式進行。 ' 卜 一種製備C19位置上經修飾之環氧噻唑酮之方法,其 將3,7-未被保濩之環氧。塞唾酮人或^在位置上金 屬化,並依習知方法經親電子試劑補捉成C19位置上 經修飾之經crc^燒基或_素取代之環氧嗔峻酮 5. 8. (請先閱讀背面之注意事項再填寫本頁} 訂---------· 經濟部智慧財產局員工消費合作社印製 Ο Me環氧σ塞嗤酮B -L. · 14 本紙張尺度適用中國國豕ί示準(CNS)A4規格(21〇 X 297公爱 480263申請專利範圍 10.根據申請專利範圍第9項之方法, 化。 /、〒以丁基鋰金屬 η·—種具下述通式之經保護或未 酮α-ν-氧化物或環氧噻唑酮Β_Ν_氧化物=之環氧嗔唑其中R=H或CH3 ; Z = 0_且R1及R2 = H或保 15 本紙張尺度適用中國國家標準(CNS)A4規格(210 χ 297公釐) 護基 經濟部智慧財產局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁)專利申請案第87102758號 ROC Patent Appln. No. 87102758 補充之實例中文本-附件(一) Supplemental Examples in Chinese - Enel. (I) 军 β — (Submitted on June f| , 2001) 環氧噻唑酮b-n-氧化物之合成 將間-氯過苯甲酸(〇·31克)於二氯甲烷(20毫升')之溶液 加至被攪拌之環氧噻唑酮Β (0.4克)於二氯甲烷(1毫升) 的溶液中。3小時後,反應以Na2S03水溶液中止,將所得 混合物分佈於飽和NaHC03水溶液及醋酸乙酯中。使合併之 有機層在MgS04上乾燥並於真空中濃縮。在RP-18矽凝膠 上使用乙腈/0.05M醋酸銨缓衝液(ρΗ7·5,35/65)藉由色層 分析分離殘留物。產率0.17克。 TLC:Rf=〇.19(矽凝膠Si60,二氯甲烷/甲醇(95/5),以香草 醛/硫酸偵測,加熱至120°C時呈現藍灰色斑; HPLC : Rf=2.8 分鐘(HD-Sil 100, C-18, 5 μηι,125X4-mm 管 柱,乙腈/水(40/60),1·5毫升/分鐘,在254nm下偵測); UV (MeOH) : λ max(s)=283 sh (1650), 263 SH (4300), 236 nm (15 500); IR (Kbr) : v=3439, 2963, 2936, 2877, 1740, 1689 cm"1 ° HR-E1-MS (70 eV) ; m/z (%) : 523.2629 (40, M+),計算值 (C27H41N07S) ; 523.2604 ; EI-MS (70 eV) : m/z (%) : 523 (40),336 (42),194 (18),182 (75),154 (100),126 (42)。 GBF87078WC-SE 0263Ab 4 Μ 子 原 l234567R910ul213ul5i6l7l82202l222324252627 std s sdludtttddtdsd 3d 3 Q^QiQ-QQ-O^Q^ (75.5 MHz 原子 5 [ppm] VUm/u 暴 3 M it ju\jiyki 顺] CDCI,) 2:Ha 2.13 dd 2o,2b=12.9 δ fppml 2-Hb 2.47 dd 2b,3=12.0 170.5 3-H 4.58 dd 2a>3-2.8 40.0 3·ΟΗ - - - 70.9 6·Μ 3,29 dq 6,7-2.0 55J 7-H 3.70 dd 7,8=5.8 22 i.4 7·ΟΗ - m - 40.7 8-H 1.7-1.9 m 7X5 9,Ha L2-1.4 m 37,3 9-Hb 1.2-1.4 m 33.2 10-Ha 1.3-1.4 m 22.0 10,Hb m 31.5 11-Ha 1.2-1.4 ra 623 U-Hb K5-I.8 m 63.0 12·Η 参 - 33.4 13-H 2.75 d 75.6 14-Ha 1.6 -1.8 m 14ϋ,141>=15.6 144,3 14-Hb 2.22 d in.i 15·Η 5.32 d 14a,l 5=10.6 143.3 17-H 6.79 bs 雄 1103 19^H 7.08 s • 145.1 21-Ha 2.60 3 - 13.4 22-H3 1.02 s • 15.3 23·Η3 1,27 s 22.2 24-H, U6 d 6,24«=6.8 12.5 2S-H3 0.99 d 8,25=7.0 16.5 26-H, 1.41 s 23.2 27.H) 2.06 b3 - 18.2 2
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Publication number | Priority date | Publication date | Assignee | Title |
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DE4138042C2 (de) * | 1991-11-19 | 1993-10-14 | Biotechnolog Forschung Gmbh | Epothilone, deren Herstellungsverfahren sowie diese Verbindungen enthaltende Mittel |
ES2178093T5 (es) * | 1995-11-17 | 2009-02-16 | Gesellschaft Fur Biotechnologische Forschung Mbh (Gbf) | Derivados de epotilon y su preparacion. |
US6441186B1 (en) * | 1996-12-13 | 2002-08-27 | The Scripps Research Institute | Epothilone analogs |
CN1128803C (zh) * | 1997-02-25 | 2003-11-26 | 生物技术研究有限公司(Gbf) | 环氧噻嗪酮b-n-氧化物及其制备方法 |
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