PAPAVERINE
Synthesis
By MOIN ULLAH
PAPAVERINE
General Info:
A
benzylisoquinoline alkaloid found in opium
plant
 Vasodilator help the to dilate blood vessels
by relaxing smooth muscle in blood vessels
 Overdose sympthoms:
Weakness, dizziness, vomiting, double
vision, sweating, faster heartbeat and
uncontrolled eye moment.
 It
has little or no analgesic( relieve pain) or
hypnotic( sleep-inducing) properties
 Drug
class:
Peripheral Vasodilator
 Given
via injection either through muscle or
veins over prolonged duration(1 to 2 min)
 Sometimes
used as an effective treatment
for male impotence but this application has
been diminished by orally in-takable
sildenafil(ViagraR)

Side effects:
Nausea(1), constipation, diarrhea,
headache, spinning sensation, uper stomach
pain, loss of appetite and Jaundice(2)
1) sickness feeling or discomfort in
the stomach that may come with
an urge to vomit
2) skin or eyes yellowing

PRODUCTION:
Precursor : L-Tyrosine
Percent present in opium : 1%
 Since
its presence is very minute an
alternate biotechnological process is
employed to produce it in large quantities
which has been demonstrated by producing
substantial quantities of reticuline in a
transgenic system, incorporating plant genes
from Coptis japonica (Ranunculaceae) into E.
coli
BIOSYNTHETIC PROCESS (IN OPIUM
PLANT)
 Firstly
two L-Tyrosine molecule got converted
into L-DOPA and 4-hydroxylphenyl-pyruvic
acid in PLP presence
 L-DOPA
yields into Dopamine and 4hydroxylphenyl-pyruvic acid into 4hydroxylphenyl-acetaldehyde via
decarboxylation and with enzyme E1’s help
 Now
Dopamine and 4-hydroxylphenylacetaldehyde combines to form (S)norcoclaurine in E2 enzyme presence
 (S)-norcoclaurine
converts into (S)-coclaurine
by replacing one of the hydroxyl- group with
methaoxy-group with the help of E3 enzyme
and SAM as regulator
 Now (S)-coclaurine converts into N-norreticuline
 And finally papaverine forms from N-norreticuline in final step via methylation and
dehydrogenation
DOPAMINE AND 4HYDROXYPHENYL-ACETALDEHYDE
FORMATION:
PART 1:
PART 2:
FORMATION OF (S)-COCLAURINE
PART 1:
PART 2:
CONVERSION OF (S)COCLAURINE
INTO N-NOR-RETICULINE:
SUCCESSIVE O-METHYLATIONS OF
N-NOR-RETICULINE :
 E1:
Aromatic amino acid decarboxylase
 E2: Norcoclaurine synthase
 E3: Norcoclaurine 6-o-methyltransferase
 PLP (Pyridoxal phosphate)
 SAM (S-Adenosyl methionine)
involved in methyl group transfers,
transsulfuration, and aminopropylation