title: Enantioselective synthesis of adamantylalanine and carboranylalanine and their incorporation into the proteasome inhibitor bortezomib.
abstract: The incorporation of adamantylalanine and carboranylalanine at the P2 site of bortezomib is well tolerated and provided potent cell permeable proteasome inhibitors with increased off-rates compared to bortezomib. Adamantylalanine and carboranylalanine were synthesized enantioselectively by an asymmetric Strecker reaction on Ellmans tert-butyl sulfinimines.
authors.affiliation: Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands. h.s.overkleeft@lic.leidenuniv.nl.
authors.forename: Gerjan
authors.initials: G
authors.lastname: de Bruin
authors.affiliation: Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands. h.s.overkleeft@lic.leidenuniv.nl.
authors.forename: Elliot D
authors.initials: ED
authors.lastname: Mock
authors.affiliation: Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands. h.s.overkleeft@lic.leidenuniv.nl.
authors.forename: Sascha
authors.initials: S
authors.lastname: Hoogendoorn
authors.affiliation: Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands. h.s.overkleeft@lic.leidenuniv.nl.
authors.forename: Adrianus M C H
authors.initials: AM
authors.lastname: van den Nieuwendijk
authors.affiliation: Crystallics B.V., Meibergdreef 31, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Mazurek
authors.affiliation: Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands. h.s.overkleeft@lic.leidenuniv.nl.
authors.forename: Gijsbert A
authors.initials: GA
authors.lastname: van der Marel
authors.affiliation: Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands. h.s.overkleeft@lic.leidenuniv.nl.
authors.forename: Bogdan I
authors.initials: BI
authors.lastname: Florea
authors.affiliation: Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands. h.s.overkleeft@lic.leidenuniv.nl.
authors.forename: Herman S
authors.initials: HS
authors.lastname: Overkleeft
mesh_terms: D000218:Adamantane / Q000138:chemical synthesis* / Q000737:chemistry; D001896:Boron Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D000069286:Bortezomib / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry* / Q000378:metabolism; D061988:Proteasome Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D013237:Stereoisomerism; D013452:Sulfonium Compounds / Q000737:chemistry
chemical_list: D001896:Boron Compounds; D061988:Proteasome Inhibitors; D013452:Sulfonium Compounds; D010649:Phenylalanine; C014388:carboranylalanine; D000069286:Bortezomib; D046988:Proteasome Endopeptidase Complex; D000218:Adamantane