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RESEARCH
PROJECT
Dottorato di ricerca-XX ciclo
DOTTORANDO: PAPANDREA GIOVANNI
TUTOR: Prof. PONTICELLI FABIO
TITLE:
Design
and
Stereoselective
Synthesis
of
Highly
Substituted
Cyclohexenes/Cyclohexanes and Cyclopentenes/Cyclopentanes
Initial scientific support:
A number of reports in the literature lead to design potential drugs in which the
cyclopentene/cyclopentane and cyclohexene/cyclohexane rings served as scaffold for
substituents (carboxilate, guanidine, acetamido, azido, alkyl, hydroxyl group, ….). We
find some of these compound in neuromidase inhibitors1 (1 and 2), in ligands for the
FP-receptor2 (3), in adenylyl cyclase inhibitors3 (4), in antiviral agents4 (5).
CO2H
CO2H
O
HO
CO2H
N
H
H
NH2
HN
X
O
NH2
HN
NHCOCH3
1
HO
OH
3
2
NH2
x= N, S
O
N
N
N
N
N
N
HN
N
NH2
OH
OH
4
5
CO2CH3
Research target :
Formation and transformations of bonds, interconversion of functional groups of easily
starting materials into complex building blocks is very important in Organic Chemistry.
Generally, in this work the starting materials are cyclic 1,3-dienes (cyclopentadienes
and cyclohexadienes) on which different functional groups will be introduced.
However, the intricate access to functionalized cycloalkenes often is the major
drawback to a practical use of these reactions. One solution to by pass this problem is
based on Diels-Alder reactions, in fact several research groups have elegantly
demonstrated the synthetic versatility of numerous organic system involving DielsAlder chemistry and many of them have just been exploited for the synthesis of
cyclopentensulfonic amino acid with good yield.
Another utility of Diels-Alder approach is the high degree of regio and stereo
selectivity, due to the concerted mechanism. As a conseguence, it is well known that
after the syn introduction of the first functional group by Diels-Alder cycloaddition,
there is a sure dependence upon the future stereochemistry of the next substituents
around the cyclopentene/cyclohexene ring tether, which will be continued to probe
through the synthesis of all possible stereoisomers. In fact, this study will be focused
not only on the rigidity of the synthetic tether, but also it will take in to account the
spatial aspects of molecules within the tether, having in mind the regio and stereoselective synthesis of all possible isomers because the biological properties of organic
molecules largely depend on their stereochemistry.
Bibliography:
1. BioCryst Pharmaceutical, J. Med. Chem., 2004, 47, 1919-1929.
2. Procter and Gamble Pharmaceutical, J. Med. Chem., 2000, 43, 945-952.
3. Danilel E. Levy et al., J. Med. Chem., 2003, 46, 2177-2186.
1. Jing Wang et al., J. Med. Chem., 2000, 43, 736-745.