Total synthesis of (-)-salinosporamide A.
A detailed description of our second-generation total synthesis of salinosporamide A is presented. Three contiguous stereocenters in the γ-lactam structure seen in the natural product were established by stereoselective functionalization of a D-arabinose scaffold, including an Overman rearrangement to generate a highly congested tetrasubstituted carbon center. One of the definitive reactions in the synthesis was a Lewis acid mediated skeletal rearrangement of a pyranose structure, which enabled the practical conversion of the carbohydrate scaffold to the γ-lactam structure embedded in salinosporamide A. The use of a benzyl ester as a protective group for a sterically hindered carboxylic acid led to a one-pot global deprotection at the end of the synthesis.
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.
Yuji
Y
Kaiya
Jun-ichi
J
Hasegawa
Takayuki
T
Momose
Takaaki
T
Sato
Noritaka
N
Chida
D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry
D007783:Lactones; D011758:Pyrroles; C475865:marizomib