PURINES - kap 24

1
PURINES - kap 24
Reaction with electrophiles at N - Protonation
2
Reaction with electrophiles at N - Alkylation
Selectivity depends on substituents and conditions
3
N7/N9 - Sterical factors (Large 6-subst)
Termodyn. control (reversible react.)
Electrophiles - cancer
4
Reaction with electrophiles at N - Acylation /
Sulfonation
Acylation products generally unstable Sulfonation
- Stable prod., selective N9
Reaction with electrophiles at N - oxidation
5
Reaction with electrophiles at C
6
Reaction with electrophiles at C
E-fil Ar subst, generally not working
Reaction with nucleophiles
7
Nu.Ar.Subst Reactivity FgtClgtBrgtI
Other leaving groups
8
Deprotonation at N
9
Deprotonation at C / C-metallation
10
Org. Lett, 2003, 4289
11
JOC 1997, 6833
12
Oxy purines
-Oxo forms
Alkylation, acylation etc
13
Replacement of O with other hetero atoms
Amino purines
Amino form
14
Alkylation, acylation etc
Diazotation etc.
15
Synthesis of Purines
Carbonyl condensations
Strategy A - Traube synth. etc
16
Carbonyl condensations
Strategy B
Cycloadditions
17
Bioactive Purines
DNA / RNA bases
Anticancer / antiviral drugs
18
Adenosin og adenosinreseptorligander
Sel. A2A antag. Parkinston /Alsheimer?
AKB PhD-lecture, august 05
Cytokinins - Plant growth hormones
19
Natural products

• Heteromines
• Isolated from Heterostemma brownii
• Treatment of tumors in Taiwanese folk medicine

Agelasines from marine sponges (Agelas spp)
Asmarines for marine sponges
Agelasine D
20
Reversine
http//www.scripps.edu/news/press/122203.html
21
Heterocycles cont. more than 2 heteroatoms in one
ring kap 26
5-membered rings Triazoles and tetrazoles
6-membered rings Triazines and tetrazines
22
5-membered rings Triazoles and tetrazoles
(pentazoles highly unstable)
More acidic - less basic comp to diazoles
Bioisostere - CO2H
23
1,2,3-Triazole
React. at N
24
React. at C
1,2,3-Triazole
25
Benzo-1,2,3-Triazole
26
1,2,4-Triazole
React. at N
React. at C
27
(No Transcript)
28
Small diff. stab. taut.
Tetrazole
Bioisostere - CO2H
React. at N
29
React. at C
30
Oxadiazoles and thiadiazoles
(thiatriazole)
- No acidic NH -Generally low basicity (cf
triazoles) -Some examles N-quart. -Few ex. Introd
of E-fils on C -Prone to Nu attack
Aromaticity (NMR shifts, bond lenghts)
31
Ring opening (esp. O-cont. rings)
C-lithiation easy, but often low stab of
lithiated prod
32
6-membered rings Triazines and tetrazines
Highly activated for Nu attack No simple react
with electrophiles
33
Diels Alder react. Leading to azines with fewer
N (see synth of pyridines, diazines)