Concise formal synthesis of (-)-salinosporamide A (marizomib) using a regio- and stereoselective epoxidation and reductive oxirane ring-opening strategy.
Expedient access to a highly functionalized 2-pyrrolidinone (8), the gamma-lactam core of 20S proteasome inhibitor (-)-salinosporamide A (marizomib; NPI-0052; 1), using a regio- and stereoselective epoxide formation/reductive oxirane ring-opening strategy is presented. Notably, the sequential construction of the C-4, C-3, and C-2 stereocenters of 1 in a completely stereocontrolled fashion is a key feature of streamlining the synthesis of intermediate 12. A related strategy is also discussed.
Ling
Taotao
T
Nereus Pharmaceuticals, Inc., 10480 Wateridge Circle, San Diego, California 92121, USA. taotao@nereuspharm.com
Potts
Barbara C
BC
Macherla
Venkat R
VR
D004852:Epoxy Compounds; D005027:Ethylene Oxide; D007783:Lactones / Q000138:chemical synthesis*; D061988:Proteasome Inhibitors; D011758:Pyrroles / Q000138:chemical synthesis*; D011760:Pyrrolidinones; D013237:Stereoisomerism
D004852:Epoxy Compounds; D007783:Lactones; D061988:Proteasome Inhibitors; D011758:Pyrroles; D011760:Pyrrolidinones; C475865:marizomib; D005027:Ethylene Oxide; C028537:2-pyrrolidone