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University of Helsinki Laboratory of Organic Chemistry
 

Laboratory of Organic Chemistry

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Laboratory of Organic Chemistry
Department of Chemistry
University of Helsinki
P.O. Box 55
FI-00014 UNIVERSITY OF HELSINKI

Chemistry of natural polyphenolics and steroids

Kuva

Project leader: Professor Kristiina Wähälä
Members: Tapio Hase, Antti Hoikkala, Tuija Jokela, Tiina Laaksonen, Eija Leppälä, Monika Pohjoispää

Flavonoid and lignan chemistry

This research is part of an interdisciplinary international research project entitled Lignans, Phytośstrogens and Human Health . Natural polyoxyflavonoids and -isoflavonoids, plant lignans and enterolignans of medical and biological interest, their precursors and metabolites and deuterium labeled analogues are synthesized for studies of their presence, biological properties and intestinal metabolism in mammals and man particularly. Many of these nonsteroidal naturally occurring compounds, also known as phytośstrogens , possess weak śstrogenic activity and are constituents of foods consumed by animals and man. The immediate motivation for this research stems from the evidence of their beneficial role in hormone based cancers and their potential importance as antitumor agents ( 1, 7'-hydroxymatairecinol).

Green chemistry synthetic methods for the regio- and isotopically selective polydeuteration are developed for polyphenolic compounds such as flavonoids, isoflavonoids, plant lignans, enterolignans and endocrine steroids. Up to ten deuterium atoms can be introduced by microwave and ultrasound techniques into these compounds. The isotopic and regiochemical purity of the polydeuterated product is verified by 2D NMR and MS techniques.

Due to the potential of phytoestrogens as health dietary factors, the demand for analytical methods that are more cost-effective and sensitive, and less time-consuming than those presently used led us to develop analytical methods based on immunochemistry. Synthesis methods for the production of phytoestrogen haptens for mono- and polyclonal antibodies are carried out.
(Wähälä, Hoikkala, Jokela, Leppälä, Pohjoispää)

Antioxidants of natural origin

This research is an extension on the research on dietary compounds and search for new plant derived food supplements, that can act as antioxidants and particularly substances that can prevent cardiovascular diseases and possibly cancer. Current research is focused on the development of isolation procedures, identification and synthesis of polyphenolics and steroid conjugates, e.g. phytosterol esters, present in domestic rape seed oil and further in comparative studies of olive oil from Mediterranean countries. (Wähälä)

Synthesis and labeling of steroids

Endocrinic estrogens and androgens, their metabolites and biologically active derivatives are synthesized and labeled with 3-6 D atoms (for example, 2 and 3 ) for use in studying their formation and estimating their levels in the human body. Similarly, methods for the preparation of deuterated standards of certain steroid structures are developed for quantitation in doping analysis. Other steroid structures such as cholesterolic compounds and bile acids are synthesized for studies of their biosynthesis in man and metabolism in the small and large intestine.

 

Environmentally benign synthetic methods are developed for estrogen derivatives to study the oxidation of low-density lipoprotein (LDL) and their role in cardiovascular diseases. (Wähälä)

Drug discovery

Synthesis, small molecule design and protein modeling studies are carried out to develop novel potential inhibitors for steroid hormone biosynthesis in order to prevent and treat certain hormonal based cancers. At present the research is focused on the discovery and synthesis of innovative pharmaceutical compounds to control the function of steroid receptors and enzymes responsible for endocrinic estrogen and androgen production. State-of-the-art molecular visualisation and computational tools (the SPROUT software package, CAESA, SYBYL, Insight II, Cerius 2 , GOLD) are used for modeling protein structure and protein-ligand interactions, and de novo ligand design. This allows the quick generation of rational drug ideas for diversity-oriented syntheses and retro synthetic analyses. Combinatorial and parallel synthetic techniques are used to create libraries of molecules for the target proteins. The products are analysed by LC-MS or GC-MS/MS or LC-NMR (500 MHz). ( Wähälä)

Green technology in practice:
Natural product synthesis in ionic liquids

The aim of this research is to develop new greener synthetic routes for certain natural products, highly promising bioactive materials that are not readily obtained in quantity from natural sources and whose synthesis has traditionally relied on unwieldy Friedel-Crafts and similar reactions. The present research is focused on using ionic liquids as a reaction media and the application of microwave reaction enhancement techniques.

Ionic liquids have been recognized as one of the new classes of solvents or materials that offer new, cleaner, green technologies in which waste streams are minimized ( the 12 principles of green chemistry ).

Ionic liquids are salts of usually an organic cation and an organic or inorganic anion(for example:

They have low melting points (< 100 ºC), which are influenced by asymmetry of the cation and the nature of the anion. Ionic liquids possess many useful properties, making them good media for homogeneous catalysis: they are able to dissolve a wide range of organic, inorganic and organometallic compounds, they are nonvolatile, inflammable, fairly non-toxic and can be easily recycled. Also, polarity and hydrophilicity/lipophilicity can be adjusted by the appropriate choice of cations/anions — ionic liquids have been referred to as “designer solvents”.