Stereocontrolled Synthesis of Methyl Silanediol Peptide Mimics

Abstract

The treatment of chiral sulfinimines with (methyldiphenylsilyl)lithium gives alpha-(methyldiphenylsilyl)sulfinamides with excellent diastereoselectivity, and in good yield. The presence of alpha-protons on the imines is also well tolerated. The sulfinamide auxiliary is easily removed via treatment with methanolic HCl and the resulting amine extended into peptide chains accordingly. The diphenylsilyl moiety is a resilient protecting group for the corresponding silanediol, which can be unmasked via treatment with TfOH, followed by aqueous hydrolysis. The crude silanediol may be isolated and purified as its corresponding bis-TMS siloxane via protection with TMSCl, and converted back to the desired silanediol via hydrolysis with aqueous KOH. Efforts to apply this approach to biologically relevant silanediol peptide mimics, with a view to protease inhibition, are described.

O-Substituted N-oxy arylsulphinamides and sulphonamides in Michael reactions

“…The formation of 6 can be explained by: (i) O→N anionic 1,2-migration of tert-butyl-dimethylsilyl (TBDMS), 6 and (ii) formation of a sulfur imine oxide intermediate. 7 A few examples of azaBrook rearrangements have been described, 8 however this hetero aza-Brook rearrangement is unprecedented. In our ongoing interest in the development of novel aziridination synthetic methods, 9 we envisaged that the intramolecular cyclisation of the obtained aza-Michael adducts could potentially lead to the corresponding aziridines.…”

Bioactive Amino Acids, Peptides and Peptidomimetics Containing Silicon

“…8.14. In cases without amides on both sides of the silane, loss of the second phenyl group is slower and more difficult [64]. Triflic acid has been routinely used for this deprotection step, but recently methods employing the much milder trifluoroacetic acid have been enumerated [61].…”

“…Skyrdstrup and Nielson were the first to demonstrate that this could be done in high yield, converting Ellman [81] sulfinimine 106 to 108 in 76 % yield, with diastereoselectivity > 95 % [64,82].…”

Enantioselective Synthesis of α‐Aminosilanes by Copper‐Catalyzed Hydroamination of Vinylsilanes

“…(2)]. [3,8] Recently, Oestreich and coworkers reported an elegant process catalyzed by a chiral N-heterocyclic carbene/copper complex using Suginome's Ph(Me) 2 SiBpin reagent [Eq. (3)].…”

“…[3,8] Recently, Oestreich and coworkers reported an elegant process catalyzed by a chiral N-heterocyclic carbene/copper complex using Suginome's Ph(Me) 2 SiBpin reagent [Eq. (3)]. [8i] However, these methods have limitations with respect to the scope of the amine, and, with the exception of the report by Oestreich and co-workers, require the use of a stoichiometric chiral auxiliary or reagent.…”