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 N H Pyrrole O Thiophene Other examples N N H Imidazole N S Thiazole N H Indole N H R'' NHR R' R=H R'=CO 2 H R'''=H Tryptophane R=H R'=H R'''=OH Serotonin R=Ac R'=H R'''=OCH 3 Melatonin N N H N N NH 2 Adenine (purine der.) N N H H 2 N R R=CO 2 H: Histidine R=H: Histamine N S N N H 3 C HO H 2 N CH 3 Thiamin (Vit B1)
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5-Membered rings (Heteroatom N, O, S) · PDF file5-membered rings - electron rich ... Pyrrole > thiophene > furan. 6-Membered rings (Heteroatom N) N ... Estrone in vivo HO H HH...
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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
Serotonin R=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 π-electrons in conjugation 4n+2 (n: 0, 1, 2,....)
S
5-membered rings - electron rich - reactive i E-fil. Ar subst.
X+ E
XEH X
EH X
EH X E
X+ E
X
EH
X
EH
X E
React. in α-position generally preferredSelectivity not always goodReact.: Pyrrole > thiophene > furan
6-Membered rings (Heteroatom N)N
Pyridine
Other examples
N
Quinoline
NN
Pyrimidine
N N
Pyridazine
Rare in nature
N
N
Pyrazine
NNH
NH2
O
Cytosine
N
Quinine
H3CO
HO
N
N
Ant pheremoneN N
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
HE
N
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 ClOMe
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.)
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’)
Translation: RNA - Protein3 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
O SO
NH2
tRNA-fMet
O SO
HNO
mRNA30S ribosoe
O SO
HNO
3'mRNA
5'
30S initiator complex
AUG
50S ribosome
3'5' AUGU A C U A C AU C
U A C
O SO
HNO
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
O SO
HNO
fMet
OHN
O
NH2Arg
NH
NH2 OH O
ONH
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
OO
O
OO
HO
B
P
OHO
O
B
OON
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
PO
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