A concise synthesis of maleic anhydride and maleimide natural products found in antrodia camphorata
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指導老師 : 詹于宜 老師 報告組員 : m96h0205 湯朝棟 m96h0231 賴詩哲 Date: 2008/06/03 PowerPoint PPT Presentation


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天然物特論期末報告. A concise synthesis of maleic anhydride and maleimide natural products found in Antrodia camphorata. 指導老師 : 詹于宜 老師 報告組員 : m96h0205 湯朝棟 m96h0231 賴詩哲 Date: 2008/06/03. 光電應用. 馬來醯亞胺也是 罕見之 非結晶性紅色螢光材料 ,用於製作 LED 。 結構式如下:. 最新的活性發現.

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指導老師 : 詹于宜 老師 報告組員 : m96h0205 湯朝棟 m96h0231 賴詩哲 Date: 2008/06/03

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A concise synthesis of maleic anhydride and maleimide natural products found in antrodia camphorata

天然物特論期末報告

A concise synthesis of maleic anhydride and maleimide natural products found in Antrodia camphorata

指導老師: 詹于宜 老師

報告組員: m96h0205湯朝棟

m96h0231賴詩哲

Date: 2008/06/03


M96h0205 m96h0231 date 2008 06 03

光電應用

  • 馬來醯亞胺也是罕見之非結晶性紅色螢光材料,用於製作LED。

  • 結構式如下:


M96h0205 m96h0231 date 2008 06 03

最新的活性發現

  • 從Antrodia camphorata中所發現的三個新結構,能夠有效抑制Lewis lung carcinoma (LLC) cell lines.其抗癌機制目前還未清楚了解。

  • 抑癌成分的結構式如下(1):


M96h0205 m96h0231 date 2008 06 03

Suzuki cross-coupling

  • 透過Pd催化的有機硼化物和鹵化烴在很溫和的條件下發生cross-coupling

  • Suzuki cross-coupling是在很溫和的條件下,不會因為水和很多官能基的影響,這種反應被大量用在實驗室製備藥物以及精細化工合成大量的有用的有機中間體。


M96h0205 m96h0231 date 2008 06 03

  • 也有Heck,Negishi,Stille,Himama,Sonogashira和Kumuda cross-coupling等類似的反應

  • 不過Suzuki cross-coupling反應條件比較溫和而且所用的各種硼酸和衍生物跟其他cross-coupling中用的有機金屬試劑來說對環境比較好,且容易保存,容易處理。含硼的副產物比其他的有機溶劑容易除去,這對於工業生產來說是很有優勢的。


Derivative

Derivative


M96h0205 m96h0231 date 2008 06 03

馬來酐的衍生物

  • THF(四氫呋喃)是一種重要的有機溶劑和精細化工產品的中間體,在化工、制藥及有機合成中有著廣泛的應用;也是中樞神經系統抑制劑,低濃度會引起頭痛。

  • 1,4-丁二醇(1,4-Butanediol, BDO)是重要的石化、醫藥、有機物原料之一,廣泛用於生產工程塑料及纖維。


M96h0205 m96h0231 date 2008 06 03

  • 反-丁烯二酸(fumaric acid)是一種麵糰改良劑,可以幫助麵包延長老化,保水性較佳,使麵糰中的雙硫結構更佳穩定,增大麵包體積。

  • 蘋果酸(malic acid),是化妝品常用的原料之一,能幫助預防體內氧氣不足的現象,也是食品調味常用的原料;此外還可以穩定血糖,預防糖尿病。


M96h0205 m96h0231 date 2008 06 03

  • 反-丁烯二酸(fumaric acid)又稱富馬酸、延胡索酸,用在製造聚酯樹脂及多元醇,作為染料的煤染劑或是調味料;此外還可以治療皮膚病。


Concise synthesis

Concise synthesis


M96h0205 m96h0231 date 2008 06 03

最終合成物


M96h0205 m96h0231 date 2008 06 03

Negishi cross-coupling


M96h0205 m96h0231 date 2008 06 03

Suzuki cross-coupling


M96h0205 m96h0231 date 2008 06 03

Scheme 1.

Negishi cross-coupling

(i)

(ii)

  • Reagents and conditions:

  • BnNH2, AcOH, 50 C, 16 h, 81%

  • (ii) Pd2(dba)3 (10 mol %), PPh3 (20 mol %), iBuZnBr, THF, 20 C, 16 h,60%


M96h0205 m96h0231 date 2008 06 03

Suzuki cross-coupling

(iii)

(iv)

Reagents and conditions:

(iii) 7, Pd2(dba)3 (10 mol %), HP(t-Bu)3BF4 (20 mol %), Cy2NMe, dioxane, 20 C, 3 h, 76%;

(iv) KOH, THF/MeOH (1:2), 78 C, 12 h then HCl (2 M), 20 C, 63%.


M96h0205 m96h0231 date 2008 06 03

Scheme 2.

(i)

(ii)

  • Reagents and conditions:

  • K2CO3, 3,3-dimethylallylbromide, acetone, 56 C, 16 h, 77%

  • (ii) (a) n-BuLi, THF, 78 C,20 min then B(OMe)3, 1.5 h, -78->20° C;

  • (b) NH4Cl (aq), 20 C, 0.5 h,59%.


M96h0205 m96h0231 date 2008 06 03

Scheme 3.

Negishi cross-coupling

(i)

(ii)

(iii)

  • Reagents and conditions:

  • BnNH2, AcOH, 50° C, 16 h, 83%

  • (ii) Ni(PPh3)2Cl2 (5 mol %), BuZnBr, THF, 20 °C, 4 h, 49%

  • (iii) Br2,AlBr3, CH2Cl2, 1 h, 0->20° C, 55%


M96h0205 m96h0231 date 2008 06 03

Suzuki cross-coupling

(iv)

(v)

Reagents and conditions:

(iv) Pd2(dba)3 (10 mol %), HP(t-Bu)3BF4 (20 mol %), Cy2NMe, dioxane, 20 C, 3 h, 56%

(v) KOH, THF/MeOH (1:2), 78 C, 12 h then HCl (2 M), 20 C, 63%.


M96h0205 m96h0231 date 2008 06 03

i to 2

ii to 3

  • Reagents and conditions:

  • Urea, 140 C, 4 h, 60%

  • (ii) NH2OHAHCl, pyridine, 100 C, 12 h, 79%.


Discussion

Discussion


M96h0205 m96h0231 date 2008 06 03

  • The natural products maleic anhydride 1 and maleimides

  • 2 and 3 have been isolated from the mycelium of

  • Antrodia Camphorata, each displaying activity in LLC

  • cell lines.

  • The paper describe a concise synthesis of each of these

  • natural compounds utilizing C–C cross-coupling

  • methodology, namely, the Negishi and Suzuki reactions.

  • This efficient and high yielding synthesis is convergent

  • lending itself to production of medicinal analogues.


The end

The End

Thank you for your attention


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