No description available.

Two research projects are described: studies of the synthesis of alpha-amino-alpha-alkylsilanes, the synthetic precursor of silanediol-based protease inhibitors, and the synthesis and stability evaluation of silanediol amino acids with an unprecedently unhindered silanediol group. Two methods were investigated as approaches to alpha-amino-alpha-alkylsilanes. First, a silicon-substituted aziridine was chosen as the precursor of an alpha-amino-alpha-alkylsilane via ring opening reactions with carbon nucleophiles. Silyl-substituted aziridines 2-24 and 2-30 were prepared via direct lithiation/silylation of aziridine and employed as substrates for ring opening reactions. In spite of many attempts to ring open these silylaziridines and prepare ?-amino-?-alkylsilanes, optimization of the reaction conditions were unsuccessful. Secondly, alpha-chloro-alpha-benzylsilane 3-12 was prepared as the precursor of an alpha-amino-alpha-alkylsilane via lithiation/benzylation. The alkylation at carbon alpha to silicon to give chloromethylsilane 3-14 was successful when using n-butyllithium for lithiation, which could be explained by the steric encumbrance inherent in the structure. Several attempts for nucleophilic displacement of chloride to obtain alpha-chloro-alpha-benzylsilane 3-11 were unsuccessful possibly due to the steric effect as well as the electronic effect of silicon on the alpha carbon which made the chloride less reactive toward nucleophilic substitution. The silanediol amino acid 4-1 was synthesized originally as a potential arginase inhibitor. Although the expected biological activity was not observed, the studies on silanediol-siloxane distribution of the silanediol amino acid revealed the unique properties of this compound. Under basic conditions, the silanediol amino acid was mainly stable in monomeric form. As the pH decreased, the silanediol amino acid gave a mixture of siloxanes which consisted of a variety of stereoisomers. With available instrumental techniques, monomer, dimers and trimers of the silanediol amino acid were identified. / Chemistry

No description available.

No description available.

Dialkylsilanediols are a novel class of non-hydrolyzable analogues of the tetrahedral intermediate of amide hydrolysis, shown to be good inhibitors of HIV-1 protease, angiotensin converting enzyme (ACE), and thermolysin. An impediment to utilization of these silanediol structures, however, has been the methods for their assembly. This research describes the reductive lithiation of hydridosilanes and alkoxysilanes, and the use of the resulting silyl anions to develop efficient methods to synthesize silanediol precursors. In the first part of research, lithiation of hydridosilanes was studied. As part of this study, a simple 1H NMR method was developed for monitoring and analyzing the progress of lithiation. In addition, this method was converted to a titration for silyllithium reagents using BHT as an internal standard. Silanediols 107 and 177 are analogues of a potent chymase inhibitor, NK-3201 (82). In the second part, diphenylsilanes 108 and 170, precursors to silanediols 107 and 177, were synthesized using addition of silyllithium to sulfinimine 113 as a key step. In the third part, lithiation of alkoxysilanes was studied. (Si,O)-Dianions, generated from lithiation of silane alcohol 175 or 2,2-diphenyl-1-oxa-2-silacyclopentane (225), were reacted with a wide variety of electrophiles to give potentially useful silicon-containing building blocks. Addition of the (Si,O)-dianion 284 to sulfinimines gave silanediol inhibitor precursors with full control of stereochemistry. In the last part, a new method featuring 1,1-diphenyl-2-azaallyllithium chemistry were utilized to synthesize a series of protected α-amino silanes 323, 329 - 331. / Chemistry