heterocycles (mcm chapt 28) monocyclic or fused rings cont. one ore more ring atom ≠ c (normally...
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Heterocycles (McM chapt 28)•Monocyclic or fused rings•Cont. one ore more ring atom ≠ C (normally O; N; S)•Aromatic, partly saturated or saturated ring(s)
5-Membered rings (Heteroatom N, O, S)
S
Thiophene
NH
Pyrrole
O
Thiophene
Other examples
N
NH
Imidazole
N
S
Thiazole
NH
Indole
NH
R'' NHR
R'
R=HR'=CO2HR'''=H
Tryptophane
R=HR'=HR'''=OH
SerotoninR=AcR'=HR'''=OCH3
Melatonin
N
NH
N
N
NH2
Adenine(purine der.)
N
NH
H2N
R
R=CO2H: HistidineR=H: Histamine
N
S
N
NH3C
HO
H2N
CH3
Thiamin(Vit B1)
X X X X X XX: S, Se
e- in d-orb.
Cyclopentadienyl anion
Thiophene
S
Criteria for Aromaticity (Hückel)(Monocyclic) ringPlanarNo of -electrons in conjugation 4n+2 (n: 0, 1, 2,....)
S
5-membered rings - electron rich - reactive i E-fil. Ar subst.
X+ E
XE
H XE
H XE
H X E
X+ E
X
EH
X
EH
X E
React. in -position generally preferredSelectivity not always goodReact.: Pyrrole > thiophene > furan
6-Membered rings (Heteroatom N)N
Pyridine
Other examples
N
Quinoline
N
N
Pyrimidine
NN
Pyridazine
Rare in nature
N
N
Pyrazine
N
NH
NH2
O
Cytosine
N
Quinine
H3CO
HO
N
N
Ant pheremone
NN
HydralazineAntihypertensive drug
H2NHN
NH
H H
H H
Pyridine as a base
N NH
+ H
NH
H H
H H
NH
H H
H H
H
pKa: 5.2
NH
pKa 0.4
NH
pKa 11.3
N
NH
pKa 7.1(≈amidine)
N
S
pKa 2.5
sp2 N less basic than sp3
Electrophilic Reaction on Carbon: E-phil. Ar. Subs.
6-membered rings - electron deficient - reactivity
N
NE
N
H
EN
E
+ E
+ res. forms
•Both C and N may react
•3/5 pos. most reactive C
•Diazines less reactive
•Sulfonation, Nitration, halogenatil
•Not FC react.
N NH
NH
H NO2
N
NO2H / NO2 H / NO2
+ res. formsBenzo ring most reactiveMuch slower react. than naphthalene
N N N N N
6-membered rings - electron deficient - reactive in Nu-fil. Ar subst.
N Cl
OMe
NOMe
Cl
+ res. form
N OMe
2 / 4 Pos. reactive; electron def. C, neg. charge partly on N in intermed3 / 5-Pos. much less reactive (benzenoid pos.)
Nucleophilic Aromatic Substitution
•SNAr
•SN1: Via arylic cation
•Benzyne
•SRN1: Involves radicals
•VNS: Vicarious nucl. Subst.
X Nu X
Nu
X
Nu
X
NuNu
Nucleosides, Nucleotides, Nucleic acids (DNA; RNA)
DNA bases
DNA Nucleosides
2-Deoxyribosides
RNA bases
HN
N
O
O
Thymidine
N
N
NH2
O
Deoxycytosine Deoxyadenosine
N
N N
N
NH2
HN
N N
N
O
H2N
O O O O
OH OH OH OH
HO HO HO HO
Deoxyguanoosine
HN
NH
O
O
Thymin
N
NH
NH2
O
Cytosin Adenine
N
N NH
N
NH2
Guanine
HN
N NH
N
O
H2N
HN
NH
O
O
Uracil
Cytosin Adenine Guanine
RNA Nucleosides
Ribosides
HN
N
O
O
Urinine
Cytosine
Adenosine
O
OH
HO GuanoosineOH
Nucleotides
OO
XHO
B
P
OO
XO
B
P
O
O
OHO
XO
B
O
O
5'
3'
Double -helix (DNA)
A-T and G-C Base pairs
NN
O
O CH3
HNN
N HH
N
N
NN
O
N
NN
ON
N
H
NH
H
H
H
DNA
Procaryotes and eucaryotes
5'
5'3'
3'
Leading strand
Lagging strand
3' 5'
5' 3'
3' 5'
3'5'
Replication
Transcription
DNA polymerase
DNA
5'
5'3'
RNA polymeraseDNA
5'
5'3'
3'5'
(+) stranded RNA
Translation
mRNA(+) stranded RNA
3'5'
Protein
3'5'
3'5'
Nucleotide sequence in DNA - genetic information
DNA helicases: UnwindingDNA binding proteins: Prevents winding backDNA primase: formation of DNA/RNA primer (from free nucleosides in cell)DNA polymerase: Catalyse elongation of new strand (5’ - 3’)
Lagging strand:DNA ligase: Connects Okasaki fragments
OO
O
T
P
OO
O
C
P
O
O
O
O
5'
3'
Template strand
OO
OH
G
P
OO
O
A
P
O
O
O
O
5'
3'
New strand
OO
O
T
P
OO
O
C
P
O
O
O
O
5'
3'
Template strand
OO
OH
G
P
OO
OH
A
P
O
O
O
O
5'
3'
New strand
Next nucleotideGuanosine triphosphate
O
P
O
O
O
O
O
O
3'
DNA
5'
5'3' RNA polymeraseDNA
5'
5'3'
(+) stranded RNA3'5'
Uracil instead of thymine
Transcription: DNA - RNA
Translation: RNA - Protein
3 RNA bases coding for one AA (see Table 28.1)
Protein synthesis occurs at ribosomes
mRNA(+) stranded RNA 5' 3'
50S
30S
Ribosom
Protein
NH3+
NH3+
CO2-
70S
initiator tRNA
OH 3'
tRNA-Met
OS
O
NH2
tRNA-fMet
OS
O
HN
O
mRNA30S ribosoe
OS
O
HN
O
3'mRNA
5'
30S initiator complex
AUG
50S ribosome
3'5'AUG
U A C U A C AU C
U A C
OS
O
HN
O
U A C
Anticodon
Codon
3'
5'
fMet
U A C
A U G C G A G C U
3'
5'
fMet
U A C
A U G C G A G C U
Arg
G C U
3'
5' A U G C G A G C U
A-site
Arg
G C U
fMetRibosomewithP-site and A-site
3'
5'
U A C
A U G C G A G C U
Arg
G C U
fMet
3'
5'
fMet
U A C
A U G C G A G C U
Arg
G C U
3'
5'
U A C
A U G C G A G C U
Arg
G C U
fMet
OS
O
HN
OfMet
OHN
O
NH2
Arg
NH
NH2OH O
O
NH
HN O
O
S
NH
NH2HN
Formyl groupProtection of N-terminal
DNA / RNA Synthesis: Protecting groups and activating groups (cf. peptide synth)
OO
O
B
P
OO
O
B
O
O
O
OO
HO
B
P
OHO
O
B
O
ON
NH3 / H2O[ox]
OO
O
B
P
OO
O
B
O
O
N
Phosphite Phosphate
acidcatalyst
OHO
O
BP
OO
O
B
O
O
NN
P
O
O N
Phosphoramidite
The Polymerase Chain Reaction (PCR, 1986)
technique for quickly "cloning”(make many copies of) a particular piece of DNA in the test tube (rather than in living cells like E. coli).
primers: short oligonucleotides (ca 20 nucleotides) precisely complementary to the sequence at the 3' end of each strand of the DNA
DNA
5'
5'3'
3'
95 oC(denaturation)
5'
5'3'
3'
Addition of primers
5'
5'3'
3'
Taq polymeraseMg2+
Nucleoside-triphosphates
5'
5'3'
3'
Repeat cycle
4 copies
Repeat cycle
16 copies
ca 1011 copies in a few hours
Tac DNA polymerase: Heat stable enzymefrom Thermus aquaticus (bacteria)in hot springs Yellowstone Nat. Park