טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentMinkovich Boris
SubjectSynthesis and Characterization of Alpha-Sila-Peptides
DepartmentDepartment of Chemistry
Supervisors ? 18? Yitzhak Apeloig
Dr. Dmitry Bravo-Zhivotovs
Full Thesis textFull thesis text - English Version


Abstract

  Carbon is the most important element constructing all known life on Earth. Can “Life” exist based on another element, for instance on silicon? Silicon is the closest analogue of carbon in the Periodic Table and thus has similar chemical properties.

  In my research we prepared the first known C-protected α-sila-dipeptide and the first cyclic sila-dipeptide, a diketo-sila-piperazine. In both compounds a silicon atom occupies the desired α-position.

  N-C(O)-(tBuMe2)2(H)Si-proline tert-butyl ester (1) was synthesized by reacting the carbamoyl chloride of L-proline tert-butyl ester with (tBuMe2)2(H)SiLi. 1 was purified by liquid chromatography (8 5 % yield). Bromination of 1 with 1,3-dibromo-5,5-dimethylhydantoine in hexane yields quantitatively N-C(O)-(tBuMe2)2(Br)Si-proline tert-butyl ester (2). Similarly, reaction of 1 with 1,3-chloro-5,5-dimethylhydantoine yields N-C(O)-(tBuMe2)2(Cl)Si-proline tert-butyl ester. Reaction of 2 with ammonia yields the desired α-sila-dipeptide, H2N(tBuMe2)2SiC(O)N-proline tert-butyl ester, (3) in 30% yield. 3 which is the first known C-protected α-sila-dipeptide, was obtained quantitatively by reacting 2 with sodium amide (NaNH2). 3 crystallizes from hexane and its structure was determined by X-ray crystallography. The X-ray structure shows that the presence of the bulky tBuMe2Si groups has a minor effect on the geometry of the proline unit and the amide bond remains nearly planar. The bond lengths of the central α-silicon to the carbonyl, to the amine group and to the other silicon atoms are all in the range of similar silicon compounds.

  LiHN(tBuMe2)2SiC(O)N-proline tert-butyl ester (4) is obtained by reaction of 3 with (Me3Si)2NLi. Reaction of 4 with the N-protected acyl chloride of L-proline yields surprisingly, the first cyclic sila-dipeptide, cyclic-HN(tBuMe2)2SiC(O)N-proline, (5), which was isolated in 50% yield as colorless crystals. 5 was characterized by NMR spectroscopy and X-ray crystallography and it is a diketo-sila-piperazine. The all-carbon diketo-piperazines are biologically and catalytically active and we therefore believe that the cyclic sila-dipeptides have the potential to be also biologically and catalytically active. These aspects will be studied in the future.