total synthesis of naturally occuring cytotoxic amide alkaloids
TRANSCRIPT
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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