Asymmetric Synthesis of Silanediol Inhibitors for the Serine Protease Coagulation Cascade Enzyme FXIa

Abstract

Silanediol peptidomimetics have been prepared, designed to inhibit the serine protease enzyme Factor XIa (FXIa) for treatment of thrombosis without complete interruption of normal hemostasis. These Arg-[Si]-Ala analogues of the FXIa substrate (FIX) are the first silanediol dipeptide analogues to carry a basic guanidine group. Control of stereochemistry was accomplished using catalytic asymmetric hydrosilylation and addition of a silyllithium intermediate to the Davis-Ellman sulfinimine.

Solvent-free synthesis of enantioenriched β-silyl nitroalkanes under organocatalytic conditions

“…Many complex natural products, bioactive molecules, and drug molecules have been synthesized on exploitation of the above-mentioned properties of organosilanes [2,[7][8][9][10][11][12][13][14]. A number of efficient catalytic enantioselective methods has been developed for the synthesis of chiral organosilanes [15][16][17][18][19][20][21][22][23][24]. Out of the chiral organosilanes, nitrosilanes are important synthetic targets as they are precursors of valuable β-aminosilanes [25][26][27].…”