DITERPENE ALKALOIDS

DR . HARISHKUMAR N . KAKRANI , PRICIPAL , C . V . M INSTITUTE OF DEGREE COURSE IN PHARMACY ( institute code : 272 ), VALLABH VIDYANAGAR 388 121 & Purvi H . Kakrani

DITERPENE ALKALOIDS
Diterpene alkaloids are a group of alkaloids with a structure similar to terpenes. Diterpene alkaloids are usually derived from kaurene. They are best known from the Ranunculaceae (Aconitum and Delphinium) and Garryaceae. These compounds are similar in structure to kaurene and other diterpenes of this series, but contain a nitrogen atom, usually of obscure origin.
07/25/11 Dr. Harish Kakrani & Purvi kakrani , Diterpene Alkaloids, CDCP 2

DITERPENE ALKALOIDS
Kaurene Other similar diterpene alkaloids are found
in Inula royaleana (Asteraceae) and in Spiraea japonica (Rosaceae).

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Dr. Harish Kakrani & Purvi kakrani , Diterpene Alkaloids, CDCP

DITERPENE ALKALOIDS
Two main structural types are found.
o One:
o Series of comparatively simple and relatively non- toxic o Amino alcohols and esters o Modelled on a C20 skeleton.

o The second group

o Based on a C19 skeleton. o More heavily substituted and much more toxic. o The best known compound, aconitine, is exceedingly toxic.

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Dr. Harish Kakrani & Purvi kakrani , Diterpene Alkaloids, CDCP

DITERPENE ALKALOIDS
These alkaloids are exceedingly toxic.
o As little as 2-5 mg of some is enough to kill an adult human.

Many of these plants have been used as traditional and other medicine, but their toxicity limits their usefulness.
o They are responsible for numerous cases of livestock poisoning.

07/25/11 Dr. Harish Kakrani & Purvi kakrani , Diterpene Alkaloids, CDCP 5

DITERPENE ALKALOIDS
Mechanism by which they are toxic is they hold sodium channels open:
o Na channels are transmembrane proteins which are fundamental for cellular communication. These proteins form pores in the plasma membrane allowing passive ionic movements to occur. o Their opening and closing are controlled by gating systems which depend on both membrane potential and time. o Neurotoxins bind to the receptor sites on these Na channels produce alterations in channel inactivation activate channels at membrane potentials more negative than do unmodified channels changes in action potential duration
07/25/11 Dr. Harish Kakrani & Purvi kakrani , Diterpene Alkaloids, CDCP 6

ACONITE

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Dr. Harish Kakrani & Purvi kakrani , Diterpene Alkaloids, CDCP

ACONITE
Synonyms: Aconite root, Bachnag, Monkshood Biological source: It is dired root of Aconitum napellus Linn., belonging to family Ranunculaceae.
o Should contain not less than 0.6% of alkaloids of aconite, of which not less than 30% should be aconitine.

Geographical source: Hungary, Germany, Spain & Switzerland

o Cultivated in England o In India, it collected from wild or cultivated from A. chasmanthum or A. ferox.
07/25/11 Dr. Harish Kakrani & Purvi kakrani , Diterpene Alkaloids, CDCP 8

ACONITE
Macroscopical Characters: o Color: Dark brown o Odour: Slight o Taste: slight that causes tingling sensation followed by numbness of tongue o Dimensions: 4-10cm in length; 1-3.5cm in width o Shape: Broad towards the crown, tapering towards the distal end o Fracture: Short & horny o Surface: Deeply wrinkled; broad end bears numerous rootlets & scars o 07/25/11 Dr. Harish Kakrani & Purvi kakrani , Diterpene Alkaloids, CDCP 9

ACONITE
Chemical constituents:
o Diterpene alkaloids: aconitine, hypaconitine, neopelline, napelline, neoline o Aconitineo Chief constituent o Ether soluble o Vary in different species of aconite

o Other constituents: aconitic acid, succinic acid, starch, traces of sparteine & ephedrine o Aconitine (Acetyl benzoyl aconine) HydrolysisBenzoyl aconine + Acetic acid o Benzoyl aconine Aconine + Benzoic acid
Hydrolysis
07/25/11 Dr. Harish Kakrani & Purvi kakrani , Diterpene Alkaloids, CDCP 10

ACONITE

Aconitine Aconine

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Dr. Harish Kakrani & Purvi kakrani , Diterpene Alkaloids, CDCP

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ACONITE
Standards:
o Ash: Not more than 5% o Acid insoluble ash: Not more than 1% o Aerial stem: Not more than 5% o Foreign organic matter: Not more than 2%

Uses:
o Highly poisonous o Used externally (liniment) in treatment of neuralgia, sciatica, rheumatism & inflammation o Analgesic & cardiac depressant o Restricted to homeopathic system of medicine only

07/25/11 Dr. Harish Kakrani & Purvi kakrani , Diterpene Alkaloids, CDCP 12

ACONITE
Substitutes:
o Japanese aconite: Aconitum unicinatum o Indian aconite: A. chasmanthum

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Dr. Harish Kakrani & Purvi kakrani , Diterpene Alkaloids, CDCP

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