APPLICATIONS OF MICROWAVES IN THE SYNTHESIS OF BIOLOGICAL SIGNIFICANT MOLECULES M. Panunzio, E. Tamanini, E. Campana, G. Martelli
ISOF-CNR Dipartimento di Chimica “G. Ciamician”
Abstract: This lecture will report how microwave
technology has been used to improve the synthesis of
some key organic compounds for preparation of
Scheme 2. Reagents and conditions: Pd2(dba)3, K3PO4, Ligand, DME Introduction
Microwave-mediated synthesis is an area of
increasing interest due to the fact that it is often III. Synthesis of Prozac ® via a Hetero Diels-Alder possible to greatly accelerate the rates of reactions or, strategy. in special cases, develop new synthetic processes [1].
Below are reported some microwave induced Fluoxetine, marketed as racemate under the processes developed in our laboratories, which will be commercial name of Prozac ®, is a potent and highly discussed.
selective inhibitor of neutral serotonin-reuptake and is
among the most important drugs for the treatment of
I. Multistep microwave mediated solvent-free psychiatric disorder and metabolic problems [6]. synthesis of 4-oxo-tetrahydro-pyridine. [2]
The interest in this synthesis resides in the presence of
the 2,3-dihydro-1H-pyridin-4-one ring in several
pharmaceuticals as alkaloid ring systems [3], azasugar
Scheme 3.
IV. Synthesis of NH-3-phenylsulfanyl-azetidinones from 1-phenylsulfanyl-3-aza-1,3-dienes.
Monocyclic azetidin-2-ones (β-lactams) are precursor of β-amino acids and β-amino alcohol which are
Scheme 1.
useful building blocks for peptides containing non-
protein amino acids. 2-Azetidinones have been used to
II. Palladium catalyzed hetereoaromatic coupling introduce the C-13 side-chain of the anticancer mediated by microwave irradiation. [5]
compound paclitaxel (taxol) and related analogues.
Heteroaromatic amines are important intermediates for
the preparation of biologically active compounds.
Current methods for the preparation of heterocyclic amines generally involve nucleophilic aromatic
Scheme 4.
substitution and typically require harsh conditions and REFERENCES
Our continuing efforts in developing microwave mediated organic reactions, with the final goal of [1] Loupy, Microwave in Organic Synthesis, finding more environmentally friendly processes and
2004, WILEY-VCH Edition.
cutting off reaction times in the preparation of small [2] Panunzio et al. Synthetic Commun. 2004, 34, libraries of biologically active compounds, led us to
study rapid and efficient methods for the synthesis of [3] Kuethe, Comins, Org Lett, 2000, 2, 855. amino substituted heteroaromatic compounds using [4] Comins, Fulp, Tetrahedron Lett, 2001, 42,
[5] Panunzio, Tamanini, St-Denis, Sabbatini,
Synthetic Commun. 2004,
[6] Robertson et al. Med. Chem. 1988, 31, 1412.
Journal of Environmental Science and Health Part A, 41:173–184, 2006Copyright C Taylor & Francis Group, LLCISSN: 1093-4529 (Print); 1532-4117 (Online)DOI: 10.1080/10934520500351884 Fecal Contamination ofAgricultural Soils Before andAfter Hurricane-AssociatedFlooding in North CarolinaMichael J. Casteel,1 Mark D. Sobsey,1 and J. Paul Mueller21Department of Environmental Sciences and En
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