Upload
ngobao
View
234
Download
1
Embed Size (px)
Citation preview
BENZO CONDENSED PYRIDINES: QUINOLINES AND ISOQUINOLINES
N
QuinolineBenzo[b]pyridine(1-azanaphtalene)
abc
123
44a
56788a
N
IsoquinolineBenzo[c]pyridine(2-azanaphtalene)
abc
12
34
4a5
6788a
Alkaloid Natural Products•Largets class of secondary metabolites, >6500 compds known•Contains N, most compds basic (alkaline), often heterocyclic•Often highly toxic•Found in certain higher plants (seldom in bacteria)•Little is known regarding why alkaloids are produced•Biosynthesis from amino acids
Quinoline alkaloids Cinchona pubescens (Kinatre) from South America
N
R
HO NH
R=OMe: Quinine (Cinchonidine epimer at C-9)
R=H: Quinidine (Cinchonine epimer at C-9)
Quinidine: AntiarytmicQuinine: Antimalaria
N CF3CF3
HO NH
Mefloquine
N Cl
HN N
Chloroquine
Dihydroquini(di)ne and der.Chiral ligandsAsym. dihydroxylation (Sharpless)
Isoquinoline alkaloidsCurare - Pilgift - Søramerikanske indianereBland. Av flere alkaloider med muskeslammende effektFlere plantekilder bl.a. Chondodendron tomentosum
MeO NMe
MeO
MeO NHMe
MeO
MeO
MeO
MeO
MeO
MeO
OMe
O
OO
O
MeO
O
HO
OOH
OMe
NR
Me
NMe
Me
R=H: TubocurarinR=Me: Wrong struct.
N N
Ex. Mivacurium kloridMuscle relax, anesthesia
Cl
N O O N
O
OCl
Esterase
Cl
N OHHO N
O
OCl
HOOH
Succinsyrekolin
Suksametonium, Curacit® “Nesset”
Isoquinoline alkaloids
Morfinanalogs, binds to opiopeptide (endorfin / enkefalin) reseptors
O OHO
N CH3
O OHHO
N CH3
H3CO OO
N CH3
H3C CH3
Thebaine Morfin
NH
OHHO OH
OH
Norlaudanosoline
NH
OH
OH
HO
HO N
O
O
O
OO O O
N
O
O
O
O
Papaverine(against spasms)
NH2
HO
CO2H
Tyr
Noskapin(not analgetic,not adiction)
O OHHO
N
Morfin
O
OHN
OH
H2N
OH
HN H
NO
OO
NH
HO
NH
O
O
S
Met-enkefalin
Tyr N-terminalin opiopeptides
N N N
pKa 5.2 pKa 4.9 pKa 5.5
Protonation Electrophilic Ar. Subst.
N
E
N
NE
N
Major isomers shownE
E
Halogenation in the Pyridine Ring
N
HClBr2
N H
Br
NH Br
H
Br BrN
H Br
H BrH
- H
N
Br
HH Br
- HBr
N
Br
N
HClBr2
N
Br
Nucleophilic Addition - Nucleophilic Ar. Subst.
N
Nu
N NuN
Nu
NNu
N
Nu
NNu
NX
N X N
X
X=halogen
Reactivity towards Nu as N NX
X
Nu-radicals (Minisci react.)attacks in the same pos.
ANRORC (Add. Of Nu., Ring Opening and Ring Closure)
NHNH
NNH2
NBr NaNH2
NBr
H NH2
NBr
H NH2
NNH2
H
NuN N
NuX N NuX + X a) X=H
b) X=Good leaving group
Oxy- and Aminoderivatives - Tautomeri
-All - isomers amino (not imino)
-“One”-Isomers:
NH
O NH
O
NHO
Tautomeric Mixt.:
NOH
NHO
Quinoid struct.: NegativeAmide: Possitive
Synthesis - Quinolines
NH2
OO
H
-2 H2O N NH2
OH
- H2O [ox]
NH
Synthesis - Isoquinolines
NH2
OO
HH
N-2 H2O
O NH2
OEtEtOH
- H2O- 2 EtOH
NNH2
OX R
X: -Cl, H
- H2O [ox]
N