Harald Zilch

Sila-substitution — a useful strategy for drug design?

Abstract Sila-substitution (C/Si-exchange) of drugs is one of the approaches currently used in the search for new biologically active organosilicon compounds. Replacement of specific carbon atoms in drugs by silicon results in changes in chemical and physicochemical properties as well as in the structure. As a consequence, the biological properties, such as pharmacological potency and selectivity and toxicity, may be influenced. Systematic sila-substitution seems to be a useful and efficient strategy in drug design and should be regarded as a complementary tool for the development of new drugs.

Enantioselective reduction of acetyldimethylphenylsilane by Trigonopsis variabilis (DSM 70714)

SummaryGrowing and resting cells of the yeast Trigonopsis variabilis (DSM 70714) can be used for the enantioselective reduction of the organosilicon compound acetyldimethylphenylsilane (1) to give optically active (R)-(1-hydroxyethyl)dimethylphenylsilane [(R)-2] in good yields. The enantiomeric purity of the isolated product was determined to be 62–86% ee depending on the substrate concentration used. Both substrate and product caused an inhibition of the reaction at concentrations higher than 0.35 and 0.5 g/l, respectively. Besides, higher substrate and product concentrations led to increased formation of the by-product 1,1,3,3-tetramethyl-1,3-diphenyldisiloxane. Considering the limiting substrate and product concentrations, it was possible to use the same biomass at least 5 times without significant loss of enzyme activity. 3-Methyl-3-phenyl-2-butanone (5) and acetyldimethylphenylgermane (7), which represent carbon and germanium analogues of 1, were also found to be accepted as substrates by Trigonopsis variabilis (DSM 70714). The reduction rates of the silicon (1) and germanium compound (7) were much higher than the transformation rate of the corresponding carbon analogue 5.

Biotransformation as a New Method for Preparing Optically Active Organometallic Compounds

Trois methodes de preparation des silanes et des germanes optiquement actifs sont utilisees. Elles font appel a des reductions enantioselectives par des micro-organismes (levure Trigonopsis variabilis), a des clivages enantio-selectifs par des esterases de foie de porc, ou a des syntheses enantioselectives par des lipases de la levure Candida cylindracea

Zum thermischen Verhalten einiger Kohlensäure[(methylphenylsilyl)methyl]ester-Derivate

Abstract The synthesis and the thermal behaviour of the (methylphenylsilyl)methyl carbonates CH3(C6H5)Si(H)CH2OC(O)X (6: X = OCH3; 7: X = Cl; 8: X = N(CH3)2) is described. 8 rearranges in toluene solution at 100 °C quantitatively to give the carbam oyloxysilane C6H5(CH3)2SiOC(O)N(CH3)2 (11), whereas neat 6 and 7 at 135 °C undergo quantitative formation of C6H 5(CH3)2SiOCH3 (12) and C6H5(CH3)2SiCl (13), respectively. The formation of 12 and 13 is explained by a rearrangement reaction (by analogy to the rearrangement of 8), follow ed by a decarboxylation. The thermally induced transformations 6 →12, 7 →13, and 8 →11 were found to be first-order reactions with half-lifes of ~2.6 h (135 °C, neat), ~4.5 h (135 °C, neat), and ~3.7 h (100 °C, in toluene), respectively.