Research

Synthesis and Use of New Chiral Auxiliaries Based upon Silicon 

Research in this area focuses mainly on the design, the development and the applications to organic synthesis of different chiral silyl moieties.

Silyl groups are well established protective groups in organic chemistry, particularly for alcohols but also for carboxylic acids and amines. The silyl derivatives are easily prepared and cleaved, and their reactivities can usually be readily controlled with the appropriate choice of the groups attached to silicon.
A general principle for the synthesis of optically active compounds is the controlled chirality transfer from a single or several stereogenic entities to a newly formed stereogenic unit. Due to its close relationship to carbon, silicon should be well suited to act as a carrier of chiral information in a lot of synthetic transformations. So far, we have shown that both silicon-based chiral auxiliaries with silicon-centered chirality[1] and with silicon-centered chirality[2] (e.g. 1 resp. 2) can be prepared with high enantiomeric purity and used efficiently for diastereoselective transformations.

Zoom (JPG, 6 KB)

[1] S. Gassman, B. Guintchin, S. Bienz, Organomet. 200120 (9), 1849-1859.
[2] M. Trzoss, J. Shao, S. Bienz, Tetrahedron 200258, 5885.

More recently it turned out that, modifying appropriately the substituents attached to silicon, these moieties can act simultaneously as protective, stereo-directing and stereoisomer-differentiating group (e.g. 3). Advantage of the versatility of these multifunctional tools can be taken in the field of organic synthesis as well as in analytics, and investigations in these directions are currently in progress.[3]

Zoom (JPG, 11 KB)

[3] M. Campagna, M. Trzoss, S. Bienz, Org. Lett., 20079, 3793-3796.

Development and Application of Analytical Methods - Mass Spectrometry

The goals of the MS investigations are primarily to elaborate new analytical tools on the basis of MS/MS and HPLC-MS/MS and to gain insights into biological processes. Polyamine alkaloids are widely distributed throughout the animal and plant kingdoms, and they exhibit a variety of important and interesting biological activities. Spider venom is known to be a source for polyamine alkaloids and has therefore attracted the attention of the scientific community. Due to the complexity of the spider venom and its availability in smallest amounts only, highly sophisticated and sensitive analytical methods are necessary for detection and characterization of polyamine alkaloids. Recently we first developed a high performance liquid chromatography (HPLC) method coupled on-line with mass spectrometry (MS) and tandem mass spectrometry (MS/MS), and then applied this technique for the structural elucidation of acylpolyamines from the venom of the spider Agelenopsis aperta andParacoelotes birulai.[1] A project with the detection and characterization of new polyamine derivatives contained in the venom of other spider species is currently in progress. Another project related to this field is the extension of an already established solid-phase method for the synthesis[2] of more complex polyamine derivatives, like N-methylated an N-hydroxylated acylpolyamines which are expected to be contained in different spider venoms. Analytical investigations of the synthetic compounds would not only support the proposed structures of the natural compounds, but also permit to deduce their fragmentational behavior and use these informations as evidence in the structure elucidation of other polyamine alkaloids.

Zoom (JPG, 31 KB)

[1] Tzouros M., Chesnov S., Bienz S., Hesse M., Bigler L., Toxicon 2005, 350-354. 
[2] Manov N., Bienz S., Tetrahedron 200157, 7893-7898.

Synthesis and Use of Natural Products and Analogs

SOLID-PHASE SYNTHESIS OF N-HYDROXYPOLYAMINES DERIVATIVES

The venom of the spider Agelenopsis potteri contains a complex mixture of linear polyamine derivatives, e.g. N-hydroxypolyamine derivatives. 

Zoom (JPG, 6 KB)

These biologically active compounds interact for example with ion channels in mammalian central nervous system and thus have a therapeutically interest for studies of brain disorders such as Parkinson’s and Alzheimer’s diseases. Construction of orthogonally protected N-hydroxypolyamines can be performed on solid phase. The required N-hydroxyl group is introduced during the cleavage of the polyamine derivative from the resin through a Cope elimination reaction [1]. Selective deprotection of either of the two terminal amino functions allows the derivatization of the N-hydroxypolyamines. 
The synthesized acyl-N-hydroxypolyamines are used as reference compounds for the study and identification of constituents of authentic venom samples of Agelenopsis potteri, applying high performance liquid chromatography coupled with mass spectrometry (HPLC-MS). 

Zoom (JPG, 28 KB)

[1] J. Seo et al. Tetrahedron 200561, 9305.