Enantioselective total synthesis of (-)-Salinosporamide A (NPI-0052).
A novel enantioselective total synthesis of 20S proteasome inhibitor Salinosporamide A (NPI-0052; 1) is presented. Key features include intramolecular aldol cyclization of 6 to simultaneously generate the three chiral centers of advanced intermediate 5, cyclohexene ring addition using B-2-cyclohexen-1-yl-9-BBN, and inversion of the C-5 stereocenter by oxidation followed by enantioselective enzymatic reduction.
Ling
Taotao
T
Nereus Pharmaceuticals, Inc., 10480 Wateridge Circle, San Diego, California 92121, USA.
Macherla
Venkat R
VR
Manam
Rama Rao
RR
McArthur
Katherine A
KA
Potts
Barbara C M
BC
D018360:Crystallography, X-Ray; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D007783:Lactones; D011758:Pyrroles; C475865:marizomib