total synthesis of naturally occuring cytotoxic amide alkaloids

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    Total synthesis of naturally occurring cytotoxic

    amide alkaloids & development of new synthetic

    methodologies

    P.Surya KumariResearch Scholar,

    Dept. of Organic Chemistry & FDW,

    Andhra University,Visakhapatnam.

    Research Director

    Dr. V. SiddaiahSr. Asst. Proffesor,

    Dept. of Organic Chemistry & FDW,

    Andhra University, Visakhapatnam.

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    INTRODUCTION

    y Piper Species have been used in traditional medicinalsystems for thousands of years, including the Chineseand the Indian systems of the medicine.

    y For years the chemistry of the piper spices has beenwidely investigated, the amides of reported to possesvarious ACAT inhibitory, cytotoxic, antimycobactirial,insecticidal, antiprotozoan, analgesic, anxiolytic and

    antidepressant activities.

    y The cytotoxic activity of these compounds againstHeLa(Human cervical carcinoma) cells was evaluated.

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    Cytotoxic Amide Alkaloids

    OMe

    MeO

    HO

    N

    O

    O

    O

    O

    NO

    O

    N

    O

    (E)-10-(benzo[d][1,3]dioxol-6-yl)-1-(pyrrolidin-1-yl)dec-9-en-1-one

    (4E,10E)-11-(benzo[d][1,3]dioxol-6-yl)-1-(pyrrolidin-1-yl)undeca-4,10-dien-1-one

    OMe

    MeO

    MeO

    N

    O

    3-(3,4,5-trimethoxyphenyl)-1-(pyrrolidin-1-yl)propan-1-one

    3-(4-hydroxy-3,5-dimethoxyphenyl)-1-(pyrrolidin-1-yl)propan-1-one

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    Synthesis of cytotoxic amide alkaloids

    Br OMe

    O

    methyl 9-bromononanoate

    O

    O

    OMe

    O

    BrPh3P OMe

    O

    O

    O

    N

    O

    O

    O

    OH

    O

    Tri phenyl phospine, THF

    1N LiHMDS in Toulene

    Piperinal, Toulene

    NaOH/MeOH,water

    DCC/Pyrrolidine

    Synthesis of (E)-10-(benzo[][1,3]dioxol-6-yl)-1-(pyrrolidin-1-yl)deca9 en-1-one:

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    y Methyl 9-Bromonononate is treated with Tri Phenyl

    Phosphine to produce to give witting reagent and this

    is treated with Piperinal in presence of toluene to

    produce olefin. The formed olefin undergo hydrolysis

    in presence of Aqueous Sodium Hydroxide to produce

    acid this acid is treated with pyrroline in presence of

    DCC to produce (E)-10-(benzo[][1,3]dioxol-6-yl)-1-

    (pyrrolidin-1-yl)deca9 en-1-one

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    Synthesis of (4E,10E)-11-(benzo[][1,3]dioxol-6-yl)-1-(pyrrolidin-1-

    yl)undeca-4,10-dien-1-one

    BrOMe

    O

    O

    O

    BrPh3POMe

    O

    O

    O

    Tri phenyl phospine, THF1N LiHMDS in Toulene

    DCC/Pyrrolidine

    Dibal-H,-68oC

    O

    O

    O

    HO

    O

    O

    OMe

    O

    OMe

    O

    OH

    O

    O

    O

    N

    BrPh3POMe

    O

    1N LiHMDS in Toulene

    NaOH/MeOH,water

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    y Methyl 9-Bromohexanoate is treated with Tri Phenyl

    Phosphine to produce to give witting reagent and this is

    treated with piperinal in presence of toluene to produce

    olefin. The formed olefin is treated with DIBAL to produce

    aldehyde this aldehyde is treated with Methyl 9-

    Bromohexanoate in presence of toluene to produce

    coupled ester. This ester is undergo hydrolysis give acid and

    treated with pyrroline in presence of DCC to produce(4E,10E)-11-(benzo[][1,3]dioxol-6-yl)-1-(pyrrolidin-1-

    yl)undeca-4,10-dien-1-one.

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    Synthesis of 3-(4 hydroxy-3,5-dimethoxyphenyl)-1-(pyrrolidin-1-yl)propan-1-

    one

    OMe

    MeO

    RO

    H

    O

    OMe

    MeO

    RO

    OMe

    O

    OMe

    MeO

    RO

    OMe

    O

    OMe

    MeO

    RO

    OH

    O

    OMe

    MeO

    RO

    N

    O

    Ph3PO

    O

    Toulene, RefluxPd/C, H2

    NaOH/ water DCC/ Pyrolidine

    R=H, CH3

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    y The substituted benzaldehyde treated with phospine to

    produce olefin. The formed olefin is undergo reduced

    in presence of Pd/C . The ester undergo hydrolysis to

    produce acid and the formed acid is treated withpyrrolidine in presence of DCC to produce 3-(4

    hydroxy-3,5-dimethoxyphenyl)-1-(pyrrolidin-1-

    yl)propan-1-one ( if R=H) 3-(3,4,5-

    trimethoxyphenyl)-1-(pyrrolidin-1-yl)propan-1-one

    (If R=CH3)

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    THANK YOU