-
Wilson, Steven Ray Haakon & Gundersen, Lise-Lotte
(2020).
Fra Tippeligaen til Champions League.
Aftenposten (morgenutg. : trykt utg.).
ISSN 0804-3116.
-
Paulsen, Britt; Fredriksen, Kim Alex; Petersen, Dirk; Maes, Louis; Matheeussen, An & Naemi, Ali-Oddin
[Vis alle 11 forfattere av denne artikkelen]
(2019).
Synthesis directed towards bioactive ent-Ageloxime D and analogues.
-
Gulbrandsen, Håkon Sætren; Serigstad, Halvard; Read, Matthew Lovell & Gundersen, Lise-Lotte
(2019).
Synthesis of hydroxyphenanthridines and hydroxypyrrolophenanthridines through intermolecular Diels-Alder reactions on furan (IMDAF).
-
Gulbrandsen, Håkon Sætren; Alfaro, Jessica; Read, Matthew Lovell & Gundersen, Lise-Lotte
(2017).
Synthesis of Electron-Deficient Tetrahydroimidazophenanthridines and Dihydroimidazophenanthridines.
-
Wåhlander, Jakob Karl Kristoffer; Balcells, David; Gundersen, Lise-Lotte & Amedjkouh, Mohamed
(2017).
A New Phosphonamide-framework as Catalyst in Diels-Alder Reactions.
-
Chamgordani, Elahe Jafari; Paulsen, Jan Christian Holgado & Gundersen, Lise-Lotte
(2017).
Selective N-alkylation of 3-methylhypoxanthine, the first synthesis of Malonganenone J.
-
Gulbrandsen, Håkon Sætren; Alfaro, Jessica; Read, Matthew Lovell & Gundersen, Lise-Lotte
(2016).
Synthesis of electron-deficient tetrahydroimidazophenanthridines (TIPs).
-
Paulsen, Jan Christian Holgado & Gundersen, Lise-Lotte
(2016).
Synthesis directed towards marine natural products: Malonganenones.
-
Wåhlander, Jakob Karl Kristoffer; Balcells, David; Gundersen, Lise-Lotte & Amedjkouh, Mohamed
(2015).
Computational Study of Phosphonamides for use in Diels-Alder Reactions.
-
Gulbrandsen, Håkon Sætren & Gundersen, Lise-Lotte
(2015).
Synthesis of C-ring functionalized phenanthridines employing intramolecular Diels-Alder of furan (IMDAF) as the key step.
-
Mahajan, Tushar Ravindra & Gundersen, Lise-Lotte
(2015).
Synthetic strategies for 8-oxoguanines, as potential inhibitors of DNA glycosylases.
-
Wåhlander, Jakob Karl Kristoffer; Amedjkouh, Mohamed; Balcells, David & Gundersen, Lise-Lotte
(2014).
Synthesis directed towards asmarine fragments and development of Lewis acid Diels-Alder catalysts.
-
Hennum, Martin; Odden, Hege Hortemo & Gundersen, Lise-Lotte
(2014).
Nitrogen substituted quaternary stereocenter from Overman rearrangement and the allyl cyanate-to-isocyanate rearrangement.
-
Paulsen, Britt & Gundersen, Lise-Lotte
(2014).
Synthesis of bioactive ent-Ageloxime D, and a structurally related terpenoid.
-
Gulbrandsen, Håkon Sætern; Gundersen, Lise-Lotte & Read, Matthew Lovell
(2014).
Construction of novel polycyclic heterocycles through intramolecular Diels-Alder reaction on furans (IMDAF).
-
Aarhus, Thomas Ihle; Fritze, Urs Fabian; Hennum, Martin & Gundersen, Lise-Lotte
(2014).
Synthetic Routes to Tetrahydrodiazepinopurines - The Heterocyclic Ring System Found in Asmarines.
-
Wåhlander, Jakob Karl Kristoffer; Amedjkouh, Mohamed; Balcells, David & Gundersen, Lise-Lotte
(2014).
Synthesis of Asmarine Fragments and Development of Lewis Acid Diels-Alder Catalysts.
-
Paulsen, Britt & Gundersen, Lise-Lotte
(2014).
Synthesis directed towards bioactive ent-Ageloxime D, and a structurally related terpenoid.
-
Hennum, Martin; Fliegl, Heike; Gundersen, Lise-Lotte & Eisenstein, Odile
(2014).
Mechanistic insights on the stereoselective nucleophilic 1,2-addition to sulfinyl imines.
-
Miller, Charlotte Marie; Benneche, Tore & Gundersen, Lise-Lotte
(2013).
Total synthesis of the prostanoids Clavulolactone II, Clavulolactone III and Carijenone.
-
Paulsen, Britt & Gundersen, Lise-Lotte
(2013).
Synthesis of Bioactive Agelasines, Analogs and Structurally Related Terpenoids.
-
Mahajan, Tushar Ravindra & Gundersen, Lise-Lotte
(2013).
Design, synthesis and biological evaluation of 8-oxoguanine derivatives as potential inhibitiors of DNA glycosylases - possible adjuvants in cancer treatment.
-
Mahajan, Tushar Ravindra & Gundersen, Lise-Lotte
(2013).
Design, synthesis and biological evaluation of 8-oxoguanine derivatives as potential inhibitiors of DNA glycosylases - possible adjuvants in cancer treatment.
-
Siah, Huey-San Melanie & Gundersen, Lise-Lotte
(2013).
Strategies to 9-Substituted-8-oxoadenines. 28. Organisk-kjemisk vintermøte.
-
Hennum, Martin; Eisenstein, Odile; Fliegl, Heike & Gundersen, Lise-Lotte
(2013).
Mechanistic insights on the stereoselective nucleophilic 1,2-addition to sulfinyl imines.
-
Paulsen, Britt & Gundersen, Lise-Lotte
(2013).
Synthesis of bioactive ent-ageloxime D.
-
Gundersen, Lise-Lotte
(2013).
Non-purine Analogs of Antimycobacterial 6-Aryl-9-benzylpurines: Synthesis, Biological Activities and Spin-off Projects.
-
Gundersen, Lise-Lotte & Torheim, Norunn K.
(2013).
Møysommelig medisinjakt.
[Internett].
www.forskning.no.
-
Gundersen, Lise-Lotte
(2013).
Cyclization reactions in construction of heterocyclic systems.
-
-
-
Hennum, Martin & Gundersen, Lise-Lotte
(2012).
Methodology towards the total synthesis of asmarines.
-
Kania, Jindrich & Gundersen, Lise-Lotte
(2012).
Synthetic studies directed towards Asmarines.
-
Read, Matthew Lovell & Gundersen, Lise-Lotte
(2012).
Synthesis of tricyclic aromatic compounds by intramolecular Diels Alder reaction on furanes (IMDAF) and water elimination under microwave conditions followed by rearomatization.
-
Hennum, Martin; Odden, Hege Hortemo; Gundersen, Lise-Lotte & Hansen, Tore
(2012).
Methodology towards the total synthesis of asmarines.
-
Kania, Jindrich & Gundersen, Lise-Lotte
(2012).
Methods for isomerisation of the double bond in N-allyl purines. Organisk-kjemisk vintermøte.
-
Gundersen, Lise-Lotte
(2011).
Organisk kjemi i utvikling av nye medisiner.
-
Gundersen, Lise-Lotte
(2011).
Synthesis directed towards Agelasines and Asmarines: Marine Antibiotics.
-
Gundersen, Lise-Lotte; Kania, Jindrich; Odden, Hege Hortemo; Proszenyak, Agnes & Vik, Anders
(2011).
Synthesis directed towards Agelasines and Asmarines; Marine Antibiotics.
-
Gundersen, Lise-Lotte
(2011).
Synthesis directed towards bioactive compounds.
-
Gundersen, Lise-Lotte; Brændvang, Morten; Khoje, Abhijit Datta; Read, Matthew Lovell & Miranda, Pedro
(2011).
Non-purine Analogs of Antimycobacterial 6-Aryl-9-benzylpurines: Synthesis and Biological Activities.
-
Munack, Steffi; Leroux, Vincent; Roderer, Katrin; Ökvist, Mats; Bryntesen, Tina & Thiemicke, Alexander
[Vis alle 10 forfattere av denne artikkelen]
(2011).
A structure-guided approach to new tuberculosis drugs – potential inhibiyors of Mycobacterium tuberculosis chorismate mutase.
-
Odden, Hege Hortemo & Gundersen, Lise-Lotte
(2011).
Synthesis of allylic amines as building blocks for asmarine analogs.
-
Siah, Huey San Melanie; Gundersen, Lise-Lotte & Gorbitz, Carl Henrik
(2011).
NMR and X-ray structural studies of 3-benzyl-8-bromoadenine.
-
Lim, Fiona S. P.; Siah, Huey San Melanie & Gundersen, Lise-Lotte
(2011).
Synthesis of 8-bromo-9-substituted purines.
-
Kania, Jindrich & Gundersen, Lise-Lotte
(2011).
Double bond migration in N-allyl purines, scope and limitation.
-
Kildahl-Andersen, Geir; Kulendrn, Aisveraya; Orji, Placid N.; Müller, Christa & Gundersen, Lise-Lotte
(2011).
Synthesis, biological evaluation and docking studies of selective, purine.based adenosine receptor antagonists.
-
Khoje, Abhijit Datta; Gundersen, Lise-Lotte; Charnock, Colin; Wan, Baojie & Franzblau, Scott
(2011).
Deaza analogs of antimycobacterial 6-aryl-9-benzyl purines: Imidazopyridines, Pyrrolopyridines and benzimidazoles.
-
Read, Matthew Lovell; Krapp, Andreas & Gundersen, Lise-Lotte
(2011).
Intramolecular Diels-Alder reaction on furan (IMDAF), resulting in new complex multicyclic fused ring systems.
-
-
-
Gulbrandsen, Håkon Sætren & Gundersen, Lise-Lotte
(2020).
Synthesis of Phenanthridine - Containing Polycyclic Ring Systems through Intramolecular Diels-Alder Reaction on Furan (IMDAF).
Universitetet i Oslo.
ISSN 1501-7710.
Vis sammendrag
The work described in this thesis focused on developing a method to synthesise a variety of organic molecules with imidazophenanthridine or pyrrolophenanthridine ring structures. These are complex structures with previously reported activities against certain cancer cell lines, and as acetylcholinesterase inhibitors, among else. Acetylcholinesterase inhibitors are potentially useful as drugs for the treatment of Alzheimer’s disease.
This newly developed route to imidazophenanthridines allow for a substitution pattern not previously reported for similar structures, namely the inclusion of electron-withdrawing groups in the phenanthridine A-ring. These types of imidazophenanthridines are relatively unexplored territory, so the synthesis route’s potential to produce a variety of different substitution patterns is important. Some of the products that were tested for biological activities displayed significant activity against certain protozoa parasites responsible for tropical diseases.
In the method developed towards pyrrolophenanthridines, an elegant solution was found to introduce one of the two characteristic hydroxyl groups observed in naturally occurring analogs. It was also discovered that some of the synthesised compounds were sensitive towards oxidation, which can be exploited in further studies to introduce additional functionality.
-
Paulsen, Britt & Gundersen, Lise-Lotte
(2020).
Total Synthesis of Agelasine F and Synthesis towards ent-Ageloxime D: Two Natural Products with Interesting Biological Activities.
Universitetet i Oslo.
ISSN 1501-7710.
Vis sammendrag
The work described in this thesis has focused on total synthesis directed towards two different
classes of secondary metabolites isolated from the Agelas sponge, ageloxime D and analogs,
and agelasine F. Ageloximes were reported to be 7,9-dialkylpurinium salts carrying a
diterpenoid side chain in the 7-position and a hydroxylamine substituent in the 6-position. The
enantiomer of the reported structure of ageloxime D was the target compound, along with two
different analogs carrying either a geranyl or geranylgeranyl side chain. The enantiomer of the
naturally occurring ageloxime D was chosen as the target compound because the enantiomer of
the side chain of ageloxime D can be bought. Starting from (+)-manool, the sidechain was
converted into (+)-copalol in four steps. There are no reported syntheses of ageloximes, and
therefore a synthetic strategy was established. Starting from 9-methylated 6-chloropurine, a
method for introducing a hydroxylamine in high yields had to be developed. As the selectivity
of the alkylation of the sidechain at
N
7 was rather poor, it was necessary to introduce a
removable directing group on the hydroxylamine.
Tert
-butyldimethylsilyl was the preferred
choice, as it is sterically demanding and possible to remove under mild conditions. The
selectivity of the alkylation at
N
7 was improved dramatically with the directing group. The
removal of the directing group was eventually performed with ammonium fluoride, yielding
ent
-ageloxime D and analogs. The compounds were tested for biological activity and
ent
-
ageloxime D and geranylgeranyl-ageloxime displayed high activity against the protozoa
causing leishmaniasis and Chagas disease in addition to
Mycobacterium tuberculosis.
Agelasines are also 7,9-dialkylpurinium salts carrying a diterpenoid side chain in the adenine
7-position. Agelasine F was synthesized starting from (
S
)-carvone, and the synthesis of the side
chain focused on avoiding and improving some key steps was the main goal. The key steps
were the introduction of the chloromethyl phenyl sulfide with the right stereochemistry,
including the formation of the silyl enol ether and the avoidance of the expensive alternative
starting material, (
S
)-pulegone. This compound has shown interesting activity against some
drug resistant strains of
M. tuberculosis in vitro
and also inhibition of Na,K-ATPase
-
Bjerkmann, Marcel & Gundersen, Lise-Lotte
(2019).
Synthesis of Novel Phenanthridin-8-ol Derivatives Functionalized in the A- and C-rings by Means of a Microwave-mediated Intramolecular Diels-Alder Cycloaddition on Furan (IMDAF) Reaction.
Universitetet i Oslo.
Vis sammendrag
By means of a microwave-mediated intramolecular Diels-Alder on furan (IMDAF) reaction,
synthesis of ten phenanthridin-8-ol derivatives, whereof nine not previously reported in the
literature, was achieved. Phenanthridin-8-ols VI were produced through IMDAF cyclization and
UV/air oxidation of o-furyl-N-alkynylaniline substrates V (Scheme i), which were produced in
high yields from readily available haloanilines I and (furan-2-yl)boronic acid II in three steps.
Similarly, 5-methyl-5,6-dihydrophenanthridines VIII were produced by IMDAF cyclization of
o-furyl-N-alkynyl-N-methylaniline substrates VII. An investigation into the behaviour of substrates V
and VII in IMDAF reactions revealed significantly diminished reactivity upon methyl substitution at
R2. As an example of functionalization at oxygen of phenanthridin-8-ol derivatives, O-methylation of
a selection of 5-methyl-5,6-dihydrophenanthridin-8-ols VIII was performed, producing corresponding
8-methoxy-5-methyl-5,6-dihydrophenanthridines IX. Diminished reactivity by methyl substitution at R2
was observed in this step as well.
-
Wåhlander, Jakob Karl Kristoffer; Amedjkouh, Mohamed & Gundersen, Lise-Lotte
(2018).
Diels-Alder reactions in synthesis and method development.
University of Oslo.
ISSN 1501-7710.
Vis sammendrag
This thesis has got two parts within the common theme of Diels-Alder reactions. One part starts with the group of natural products called asmarines. These compounds, which were found in the red sea sponges, were believed to have anti-cancer properties. However a synthetic pathway to these compounds does as of yet not exist. A potential synthetic pathway for a fragment of the asmarines was devised, using a Diels-Alder reaction in a crucial step. The other part starts with thioureas, a class of compounds that act as Diels-Alder catalysts by way of hydrogen bond activation of and α,β-unsaturated carbonyl compound. A new, but similar, phosphordiamide based framework that was hypothesized to act in a similar manner to the thioureas. It was thought that a functioning phosphordiamide catalyst could be used in the crucial Diels-Alder reaction of the asmarine fragment. A more in detail description is found in Chapter 1.
In Chapter 2 the initial attempts at producing a functional phosphordiamide catalyst are presented. A few simple catalysts are produced and evaluated using several different systems. The compounds are however unsuccessful as Diels-Alder catalysts. Further studies of phosphordiamides can be found in Chapter 3 which deals with a computational study a new set of phosphordiamide catalysts, with more successful results. The Chapter 4 deals with the previously discussed synthetic pathway of an asmarine fragment. The idea of using a phosphordiamide as a catalyst was discarded in favor of a Lewis acid catalyst. Though the synthesis of the fragment was not complete, the main Diels-Alder step was eventually overcome and several more steps were completed with good yields. The final Chapter 5 describes a possible continuation to both projects.
-
Serigstad, Halvard & Gundersen, Lise-Lotte
(2018).
Synthesis of 8-hydroxyphenanthridines employing Intramolecular Diels-Alder of Furan as the key step.
Universitetet i Oslo.
Vis sammendrag
Abstract A synthetic strategy towards 8-hydroxyphenanthridines (6) was previously developed in our group, where intramolecular Diels-Alder of furan (IMDAF) was the key step. This was a continuation of a previous work as well. This strategy turned out to be not very efficient and a new and more robust strategy was planned out. The new strategy doesn’t involve diastereomers and is focused on obtaining 8- hydroxyphenanthridines in high yields, which later on can be explored for a fully functionalized ring c.
-
-
Mahajan, Tushar Ravindra; Gundersen, Lise-Lotte & Dalhus, Bjørn
(2016).
Design, synthesis and biological evaluation of 8-oxoguanine derivatives as DNA glycosylase inhibitors and efficient functionalization of 2-amino-6-chloropurines at C-8 via lithiated species.
Universitetet i Oslo.
ISSN 1501-7710.
Vis sammendrag
Resistance to chemotherapy and/or radiotherapy limits the effectiveness of cancer treatment. One factor that can contribute to resistance is the process of DNA repair. Among the different DNA repair pathways, the base excision repair (BER) is a multi-step, multi-enzyme pathway that is able to recognize and correct small changes in native nucleobases of the DNA. 8-Oxoguanine DNA glycosylase (OGG1) is one of the enzymes in this pathway which removes the oxidized guanine lesion from DNA. Inhibitors of OGG1 might improve the outcome of certain cancer treatments by temporarily inhibiting the BER pathway in tumour cells and may act as adjuvants in cancer treatment. It was envisaged that 8-oxoguanine derivatives may act as OGG1 inhibitors as they contain the signature scaffold of oxidized native guanine. The present thesis is focused on the design and synthesis of 8-oxoguanine derivatives and their biological evaluation as DNA glycosylase inhibitors.
Suitable synthetic strategies were developed to obtain 8-oxoguanine derivatives with various N-9 substituents. The 8-oxoguanines were efficiently synthesized using a threestep strategy: N-alkylation of guanine precursors at N-9, C-8 bromination and hydrolytic cleavage of bromide.
Purines are known to give varying ratio of N-9/ N-7 regioisomers depending on the nature of substituents and methods of N-alkylation. Two guanine precursors were alkylated by different N-alkylation strategies viz. base induced alkylation, Mitsunobu coupling, and palladium catalyzed allylation. The regioisomeric outcome of these strategies was studied. In the next step, N-9-alkylated purines were brominated either by direct bromination or by a lithiation/halogenation protocol depending on the nature of the substituent and its compatibility with brominating conditions. Finally, the brominated derivatives were hydrolyzed to the target compounds, 8-oxoguanine derivatives, during which the partially hydrolyzed 6-chloro-8-oxoguanine derivatives were also isolated. The 8-oxoguanine derivatives and 6-chloro-8-oxoguanine derivatives were evaluated for their ability to inhibit OGG1 using an OGG1 assay. The synthesized compounds showed a moderate inhibitory effect on OGG1.
During the course of the study, 9-alkylated 2-amino-6-chloropurine in the presence of a strong base such as LDA, gave the ring-opened products. 9-Alkylated 2-amino-6- chloropurines were functionalized at C-8 via lithiation/halogenation protocol using appropriately protected 2-amino-6-chloropurine. The scope of the C-8 lithiation was evaluated using various electrophiles.
The findings of the work will be useful in choosing efficient synthetic strategies for new derivatives of 8-oxoguanines and 6-chloro-8-oxoguanines for future development of DNA glycosylase inhibitors.
-
-
-
Mai, Ngan Thi Kim & Gundersen, Lise-Lotte
(2015).
C-C Bond Formation in the Purine 8-Position by Addition of Allylmetals.
Universitetet i Oslo.
Vis sammendrag
8-Substituted purines have been extensively studied as for example anticancer or antiviral drugs. C-C Bond formation at the purine 8-position has been most commonly done via 8-halopurines, e.g. Pd-catalyzed coupling reactions. Meanwhile, direct conversion of purines not substituted at C-8 to 8-alkylpurines seems to be promising but there are few reports in the literature. In this thesis, addition of an allylmetallic reagent to 8-unsustituted purines followed by oxidation of the adduct to form 8-allylated purines will be discussed.
-
-
Gulbrandsen, Håkon Sætren & Gundersen, Lise-Lotte
(2014).
Synthesis of C-Ring Functionalized Phenanthridines employing Intramolecular Diels-Alder of Furan (IMDAF) as the Key Step.
7Letras.
-
-
-
Marzouk, Victor Heshmat Rezkallah & Gundersen, Lise-Lotte
(2013).
Synthesis directed towards tricyclic heterocycles with DNA intercalating properties.
Universitetet i Oslo.
Vis sammendrag
4-Substituted pyrido[1,2-e]purines as anticancer agents have the ability to intercalate with DNA molecules and display improved cytotoxic activities especially towards the resistant cancer cell lines (MCF7R). These compounds were originally synthesized from imidazopyridines via poor yielding synthetic routes. Herein we discuss the development of more efficient strategies towards pyrido[1,2-e]purines. Since pyrido[1,2-e]purines vary mostly by their 4-substituent, we also wanted to develop more efficient strategy where the 4-substituent can be introduced in the last step.
-
-
-
Lim, Fiona Shiao Ping & Gundersen, Lise-Lotte
(2011).
Functionalization of the purine 8-position via 8-purinyl anions; scopes and limitations with respect to substituents at N9.
7Letras.