Stereocontrolled synthesis of methyl silanediol peptide mimics.
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.
Nielsen
Lone
L
Center for Insoluble Protein Structures, Department of Chemistry and Interdisciplinary Nanoscience Center, University of Aarhus, Langelandsgade 140, 8000 Aarhus C, Denmark.
Lindsay
Karl B
KB
Faber
Jesper
J
Nielsen
Niels Christian
NC
Skrydstrup
Troels
T
D006868:Hydrolysis; D007097:Imines / Q000737:chemistry; D008094:Lithium / Q000737:chemistry; D008968:Molecular Conformation; D018716:Molecular Mimicry; D009942:Organometallic Compounds / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D012821:Silanes / Q000138:chemical synthesis* / Q000737:chemistry* / Q000302:isolation & purification; D013237:Stereoisomerism; D013452:Sulfonium Compounds / Q000737:chemistry
D007097:Imines; D009942:Organometallic Compounds; D010455:Peptides; D011480:Protease Inhibitors; D012821:Silanes; D013452:Sulfonium Compounds; C475536:silanediol; C522016:sulfinimine; D008094:Lithium