what are alkaloids? ‘any non-peptidic & non- nucleotide ...secure site...

What are Alkaloids?

‘any non-peptidic & non-nucleotide nitrogenoussecondary metabolite’

48SCH 511 Dr. Solomon Derese

Sparteine

N

N

H

H

Lysergic acid

NH

HNO

OH

Quinine

HO

N

H

O

N

N

H Coniine

NicotineN

N

Clavulanic acid

N

O

O

OH

HCO2H

H

Retronecine

N

OHHOH

Strychnine

O

N

O

NH

H

HMorphine

HO

O

HOH

N

SCH 511 49Dr. Solomon Derese

Alkaloids have one or more nitrogen,typically as primary, secondary, or tertiaryamines, and this usually confers basicity tothe alkaloid, facilitating their isolation andpurification since water-soluble salts can beformed in the presence of mineral acids.There also alkaloids which are neutral.

The name alkaloid is in fact derived fromalkali.


The nitrogen atoms in alkaloids originatefrom an amino acid, and, in general, thecarbon skeleton of the particular aminoacid precursor is largely retained intactin the alkaloid structure, though thecarboxylic acid carbon is often lostthrough decarboxylation.


The most common amino acids from whichalkaloids are derived from are:

II) LysineI) Ornithine

NH2 NH2O

HO

lysineNH2

NH2

O

HO

ornithine

III) Tryptophan

NH2

NH

O

OH

tryptophan


V) PhenylalanineIV) Tyrosine

H2N

OHOHO

tyrosine

N O

OH

nicotinic acid

VI) Nicotinic acid

NH2

O OH

phenylalanine


Decarboxylation


Ornithine contains both d - and a - aminogroups, and it is the nitrogen from theformer group which is incorporated intoalkaloid structures along with the carbonchain, except for the carboxyl group.

NH2

NH2

O

HO

Ornithine

ad

Non-protein amino acid


NH2HO

O

NH2

Ornithine

PLP

CO2

NH2H2N

Putrescine

NH2RHN

Alkylation

OXIDATIVE DEAMINATION

HRHNO

N

R

Pyrolidine alkaloids

OXIDATIVE DEAMINATION

R NH2

H2N NH2n

Monoamineoxidase R

O

H

Diamineoxidase

H2N n

O

H


N

R

Iminium salt

O

SCoA O

O

Malonyl CoA

N

RO

SCoA

[O]

O

SCoA

O

O

N

RO

OSCoA

N

RO

HO

OSCoA

Enz B H

N

OO

CoASR

N

OHO

CoASR

N

OO

CoASR

N

O

R

+ H2O

- CO2

NR

O


N O

NADPH

N OHO

CoAS

O

ON

Tropinone

N

CO2Me

O

O


PLP

CO2

OXIDATIVE

DEAMINATIONNH2

CO2H

NH2

Lysine

NH2 NH2

Cadaverine

NH2 O NPiperideine

H

N

H

O O

SCoA

OH O

SCoAN

HO

O

SCoA

+ H2O

- CO2N

HO

Pelletierine

SAM

N

O

N-Methylpelletierine

N

H

NH

O

N

H

AnaferineSCH 511 59Dr. Solomon Derese

NH2

NH

OOH

Tryptophan

PLP

- CO2 NH

Tryptamine

NH2 2 SAM

NH

N

NH

N

OH

Psilocin


NH

Tryptamine

NH2

OO

O

O Glucose

O H

Secoganin

NH

NH

OO

O

O Glucose

Strictosidine


HONH2

OH

OL-tyrosine


HO

H

O HO H2N

HO+ HO N

HO

HO

H

HO NH

HO

H

HO

SAMHO NMe

MeO

H[O]HO NMe

MeO

HHO

MeO HO

SAM

Reticuline


HONMe

MeO

HHO

MeOReticuline

HONMe

MeO

HHO

MeOBoldine

o,o

HONMe

MeO

H

MeO

o,pOH

NMe

H

MeO

OH

O

O

Bulbocapnine

OXIDATIVE COUPLINGSCH 511 64Dr. Solomon Derese

NH2

O OH

phenylalanine


NH3

O O

phenylalanine

- NH3 SCoA

O

HSCoA

-Oxidation SCoA

O

OPyruvate

O

O

O

O

Transamination

O

NH2

SAM

OH

NHMe

OH

NH2

NADPH

NADPH

(–)-ephedrine

(+)-norpseudoephedrine

SAM

OH

NHMe

(+)-pseudoephedrine

(–)-cathinone

KHAT =MIRAA


Khat (Catha edulis, family Celastraceae;Arabic: :Somali ;قات Jaad; pronounced[ˈkæt]; Ge'ez ጫት čāt; miraa in Kiswahili), isa flowering plant native to tropical EastAfrica and the Arabian Peninsula.

Khat contains the alkaloid called cathinone,an amphetamine-like stimulant whichcauses excitement, loss of appetite, andeuphoria. In 1980 the World HealthOrganization classified khat as a drug ofabuse that can produce mild to moderatepsychological dependence.


N O

OH

nicotinic acid


N

NH2

O

Nicotinamide

N

O

O

Tigonelline

N

NH

Nicotine

N

NH

H

NornicotineN

NH

H

Anabasine

Ornithine

Lysine


N

N

MeH

Nicotine

NNicotinic acid

OH

O

H

H

NADPH

Dihydronicotinicacid

- CO2

N

O

OH

H

H

NH

N

MeFrom L-orinthine

N

N

MeH

H

H

H

NADP


NH From L-lysine

N

H

H

H

NADP

Nicotinic acidN

H

N

HH

N

N

HH

Anabasine


N

Nicotinic acid

1,2-Dihydropyridine

H

Enamine-Imine

tautomerizationN

1,4-Dihydropyridine

N

N

HH

Anatabine

N

H

N

H


what are alkaloids? ‘any non-peptidic & non- nucleotide ...secure site...

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