I. M. Lazarev

Drug design based on the carbon/silicon switch strategy

Classical bioisosteric substitution is the replacement of a carbon atom by a silicon atom (sila-substitution, carbon/silicon switch). The review is focused on the effects of bioisosteric carbon/silicon switch on the activity of the known pharmaceuticals. In the majority of cases, silicon derivatives show enhanced biological activities and improved pharmacological profiles as compared with the parent carbon drug scaffolds.

35Cl NQR Spectra of SnCl4 Complexes with Methylaryl Ethers

SnCl4 Complexes with methylaryl ethers and their 35Cl NQR spectra have been obtained. All these complexes, except SnCl4 · 1,2-(CH3O)2C6H4, have a trigonal-bipyramidal structure. The latter compound has an essentially distorted octahedral structure. One of the ligand oxygen atoms takes part in the formation of the SnCl4 complex with 1,3-, 1,4-(CH3O)2C6H4 and RNO2. These complexes have a trigonal-bipyramidal structure too.

Silicon-containing analogs of camptothecin as anticancer agents

The plant pentacyclic alkaloid camptothecin and its structural analogs were extensively studied. These compounds are interesting due to the antitumor activity associated with their ability to inhibit topoisomerase I in tumor cells. During the last decades of the 20th century, a large number of the silicon‐containing camptothecins (silatecans) were synthesized. 7‐tert‐Butyldimethylsilyl‐10‐hydroxy‐camptothecin (DB‐67 or AR‐67) has enhanced lipophilicity and demonstrates a antitumor activity superior to its carbon analog. To date, certain silatecans are under clinical trials and their ultimate role in cancer therapy appears promising. In this review, we present chemical methodologies for the synthesis of silicon‐containing camptothecins, their chemical properties, biological activity, and results of clinical trials.

Synthesis and structure of potentially biologically active N-(silylmethyl)tetrahydropyrimidin-2-ones

A transsilylation of 1,3-bis(trimethylsilyl)tetrahydropyrimidin-2-one with (chloromethyl)-chlorosilanes ClCH2SiMenCl3–n (n = 0, 2) gave the corresponding 1,3-bis[(chlorosilyl)-methyl]tetrahydropyrimidin-2-ones. New Si-containing tetrahydropyrimidin-2-ones were synthesized by the exchange reactions at the Si—Cl and Si—N bonds of these compounds. The structures of all the synthesized compounds were confirmed by multinuclear NMR spectroscopy. Virtual screening using the PASS program showed that these compounds can exhibit certain types of biological activity with 40—94% probability.

Silicon-containing dimethylphosphoric acid amides

Abstractα-Silylmethylamines MeNHCH2SiMen(OMe)3−n(n=0, 2) were involved into Todd-Atherton reaction with (MeO)2P(O)H giving N-methyl-N-trimethoxysilylmethyl-and N-methyl-N-dimethyl-(methoxy)silylmethylamides of dimethylphosphoric acid. A reaction of these compounds with BF3·Et2O led to the formation of the corresponding N-methyl-N-trifluoro-and N-methyl-N-(dimethyl)fluorosilylmethylamides of dimethylphosphoric acid. (MeO)2P(O)N(Me)CH2SiF3 existed as an (O-Si)-chelate with a pentacoordinate silicon due to the occurrence of a rare and unstudied intramolecular coordinating interaction P=O → Si.

Synthesis of chloromethyl(isopropoxy)diphenylsilane

Chloromethyl(isopropoxy)diphenylsilane was synthesized by the reaction of chloro-(isopropoxy)diphenylsilane with a binary mixture P(NMe2)3—CH2BrCl.

Si–C bond cleavage in N-[(trimethoxysilyl)methyl)]amine by methanol

The chemistry of N-(silylmethyl)amines RRRSiCH2NRR having the silyl group in the α-position is one of most actual and rapidly developing areas of organoelemental chemistry [1, 2]. A steady interest to these compounds is due to combination in the geminal fragment N–CH2–Si the basic (N atom) and acidic (Si atom) centers and, as a consequence, specific physicochemical properties [3, 4]. The chemistry of N(triorganylsilyl)amines is well studied and its particular aspects have found application in synthetic organic chemistry [5–7]. Although the primary N-[(triethoxysilyl)methyl]amine NH2CH2Si(OEt)3 was first synthesized in the 70s of the last century by heating a mixture of ammonia and chloromethyltriethoxysilane [8], its chemical properties are so far poorly studied. Apparently, this is due to both difficulties of its preparation (necessity of operating under high pressure) and a high hydrolytic instability.

Stereoelectronic structure and self-association of N-trimethylsilylsulfonamides RSO2NHSiMe3 (R = Me, CF3, Ph)

The effect of trimethylsilyl group Me3Si on the intramolecular electronic interactions and acid-base properties of N-trimethylsilylmethanesulfonamide, N-trimethylsilyltriflamide, and N-trimethylsilylbenzenesulfonamide was studied by the methods of quantum chemistry (DFT/B3LYP/6-311+G**, NBO-analysis). Structural effects of the O- and N-protonation of these N-trimethylsilylsulfonamides and their isostructural carbon analogs were investigated.

Synthesis of [(N-acetyl-N-methyl)aminomethyl](dimethyl)silyl nitrate

Transsilylation of N-methyl-N-trimethylsilylacetamide with chloromethyl(dimethyl)silylnitrate ClCH2SiMe2ONO2 led to the formation of (N-acetyl-N-methyl)aminomethyl](dimethyl)silyl nitrate, the (O–Si)-chelate with the intramolecular coordination C=O→Si bond. Spectral characteristics of this compound and the reaction product of N-[chloro(dimethyl)silylmethyl]-N-methylacetamide with silver nitrate are identical.

Conformational structure of N-(silylmethyl)anilines PhNHCH2SiMen(OEt)3-n (n = 0–3)

As show the data of IR spectroscopy and quantum-chemical calculations (B3LYP/6-311+G**), N-(silylmethyl)anilines PhNHCH2SiMen(OEt)3−n in inert media have an intramolecular hydrogen bond NH⋯OSi. N-[(Trimethylsilyl)methyl]aniline PhNHCH2SiMe3 in inert solvents exists as a mixture of two conformers close in energy.