Diastereoselective synthesis of pitavastatin calcium via bismuth-catalyzed two-component hemiacetal/oxa-Michael addition reaction.
An efficient and concise asymmetric synthesis of pitavastatin calcium (1) starting from commercially available (S)-epichlorohydrin is described. A convergent C1 + C6 route allowed for the assembly of the pitavastatin C7 side chain via a Wittig reaction between phosphonium salt 2 and the enantiomerically pure C6-formyl side chain 3. The 1,3-syn-diol acetal motif in 3 was established with excellent stereo control by a diastereoselective bismuth-promoted two-component hemiacetal/oxa-Michael addition reaction of (S)-α,β-unsaturated ketone 4 with acetaldehyde.
Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, People's Republic of China. rfchen@fudan.edu.cn wywin8@163.com.
Fangjun
F
Xiong
Haifeng
H
Wang
Lingjie
L
Yan
Lingjun
L
Xu
Yuan
Y
Tao
Yan
Y
Wu
Fener
F
Chen
D000080:Acetals / Q000737:chemistry*; D001729:Bismuth / Q000737:chemistry*; D002118:Calcium / Q000737:chemistry*; D002384:Catalysis; D007659:Ketones / Q000737:chemistry*; D008956:Models, Chemical; D015394:Molecular Structure; D011804:Quinolines / Q000737:chemistry*; D013237:Stereoisomerism; D013696:Temperature
D000080:Acetals; D007659:Ketones; D011804:Quinolines; C108475:pitavastatin; D002118:Calcium; D001729:Bismuth