Dr. George Varvounis

 

Dr. George Varvounis

Invited

Organic Chemistry

University of Ioannina, Greece.

 

Bio Data:

 

Dr. George Varvounis received a B.S. degree from the Polytechnic of Central London, England and completed his Ph.D. at the University of Salford. After two years of postdoctoral work at Queen Elizabeth College, University of London, he joined the University of Ioannina, Greece.  Dr. Varvounis research interest is in the Design, synthesis, and study of the chemical properties of novel heterocyclic compounds of pharmacological significance.

 

Selected publications:

1. Boroles. Varvounis, G. «Comprehensive Heterocyclic Chemistry III», Katritzky, A. R.; Ramsden, C. A.; Scriven, E. F. V.; Taylor, R. J. K. (eds.), Elsevier Oxford. Vol. 3, 2008, pp 1225-1241.

 

2. Tele Nucleophilic Substitutions of Hydrogen in m-(Trichloro-methyl)nitrobenzenes with Cyano and Ester Carbanions. Surowiec, M.; Belekos, D.; Makosza, M.; Varvounis, G. Eur. J. Org. Chem. (2010), 3501-3506.

 

3. Novel Thermal and Microwave-Assisted Facile Route to Naphthalen-2(1H)-ones via an Oxidative Alkoxylation-Ring-Opening Protocol. Dolka, C.; Hecke, K. V.; Meervelt, L. C.; Petros G. Tsoungas, P. G.; Eycken, E. V. D.; Varvounis, G. Org. Lett. (2009), 11, 2964-2967.

 

Abstract:

 

REACTIONS LEADING TO NOVEL PYRROLOBENZO–DIAZEPINES AND –DIAZOCINES WITH PHARMACOLOGICAL INTEREST

 

George Varvounis

Department of Chemistry, Section of Organic Chemistry and Biochemistry, University of Ioannina, 451 10 Ioannina, Greece

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Synthetic chemists have shown interest in pyrrolobenzodiazepines since the middle of the 1960s when anthramycin, a pyrrolo[2,1-c][1.4]benzodiazepine isolated from Streptomyces rufuineus, was found to possess cytostatic and antitumour properties.1 Among the important pyrrolo[2,1-c]-[1.4]benzodiazepines VPA-985 (Lixivaptan) stands out as an arginine vasopressin (AVP) antagonist. VPA-985 is an orally active, selective, non-peptide antagonist that blocks AVP from binding to V2 receptors of the distal nephron and thus causing retention of water by the kidneys. The pioneering work on VPA-985 has been undertaken by Albright and co-workers2 and is currently undergoing phase III clinical trials that involve patients with hyponatremia including those with concomitant heart failure. We will present the synthesis of the first structural isomer of VPA-985, pyrrolo[1,2-c][1.3]benzodiazepine 2, in 7 steps from (2-aminophenyl)(1H-pyrrol-2-yl)methanone 1.

The occurrence of medium-sized rings with two nitrogen atoms in biologically active compounds is known to increase the pharmaceutical strength of the compounds. A good example is the diazocine ring. The attachment of octahydro-1,4-diazocines to guanidine has produced derivatives of superior anti-hypertensive activity to that of guanidine.3 Using this principle, we decided to undertake a novel synthesis of the pyrrolo[2,1-c][1,4]benzodiazocine ring system 44 by a Dieckmann condensation of diester 3 requiring K2CO3 in DMSO at relatively high dilution. Surprisingly, the use of K2CO3 in acetone for the cylisation of 3 afforded instead 1H-pyrrole-2-carboxylic acid 5 while attempted cyclisation of cyanoester 6 with K2CO3 in acetone afforded 1H-pyrrolo[2,1-c][1,4]oxazin-4-yl)quinazolin-4(3H)-one 7. A mechanistic rationale for the formation of compounds 4, 5 and 7 will be presented.

References

1. Thurston, D. E.; Bose, D. S. Chem. Rev. 1994, 94, 433.

2. Sum, F.-W.; Dusza, J.; Delos Santos, E.; Grosu, G.; Reich, M.; Du, X.; Albright, J. D.; Chan, P.; Coupet, J.; Ru, X.; Mazandarani, H.; Saunders, T. Bioorg. Med. Chem. Lett. 2003, 13, 2195.

3. Mull, R. P.; Mizzoni, R. H.; Dapero, M. R.; Egbert, M. E. J. Org. Chem. 1962, 5, 944.

4. Koriatopoulou, K.; Karousis, N.; Varvounis, G. Tetrahedron 2008, 64, 10009.

Acknowledgement: This research was funded by the programme "Heraklitos" of the Operational Programme for Education and Initial Vocational Training of the Hellenic Ministry of Education under the 3rd Community Support Framework and the European Social Fund to G. Rotas and G. Varvounis.

The Sixth Jordanian International Conference of Chemistry
Correspondence should be addressed to: Prof. Idrees Al-Momani.
Contact Information Phone :+962  2  7211111
Fax :+962  2  7211117
chemistry2011@yu.edu.jo
http://www.yu.edu.jo/jicc
Location
Chemistry Department
Yarmouk University
Irbid
Jordan