what are alkaloids? ‘any non-peptidic & non- nucleotide ...secure site...
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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.
SCH 511 50Dr. Solomon Derese
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.
SCH 511 51Dr. Solomon Derese
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
SCH 511 52Dr. Solomon Derese
V) PhenylalanineIV) Tyrosine
H2N
OHOHO
tyrosine
N O
OH
nicotinic acid
VI) Nicotinic acid
NH2
O OH
phenylalanine
SCH 511 53Dr. Solomon Derese
Decarboxylation
SCH 511 54Dr. Solomon Derese
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
SCH 511 55Dr. Solomon Derese
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
SCH 511 56Dr. Solomon Derese
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
SCH 511 57Dr. Solomon Derese
N O
NADPH
N OHO
CoAS
O
ON
Tropinone
N
CO2Me
O
O
SCH 511 58Dr. Solomon Derese
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
SCH 511 60Dr. Solomon Derese
NH
Tryptamine
NH2
OO
O
O Glucose
O H
Secoganin
NH
NH
OO
O
O Glucose
Strictosidine
SCH 511 61Dr. Solomon Derese
HONH2
OH
OL-tyrosine
SCH 511 62Dr. Solomon Derese
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
SCH 511 63Dr. Solomon Derese
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
SCH 511 65Dr. Solomon Derese
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
SCH 511 66Dr. Solomon Derese
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.
SCH 511 67Dr. Solomon Derese
N O
OH
nicotinic acid
SCH 511 68Dr. Solomon Derese
N
NH2
O
Nicotinamide
N
O
O
Tigonelline
N
NH
Nicotine
N
NH
H
NornicotineN
NH
H
Anabasine
Ornithine
Lysine
SCH 511 69Dr. Solomon Derese
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
SCH 511 70Dr. Solomon Derese
NH From L-lysine
N
H
H
H
NADP
Nicotinic acidN
H
N
HH
N
N
HH
Anabasine
SCH 511 71Dr. Solomon Derese
N
Nicotinic acid
1,2-Dihydropyridine
H
Enamine-Imine
tautomerizationN
1,4-Dihydropyridine
N
N
HH
Anatabine
N
H
N
H
SCH 511 72Dr. Solomon Derese