Lactone pathway to statins utilizing the Wittig reaction. The synthesis of rosuvastatin.
The first entry to statins via lactonized side chain is reported, exemplified by the synthesis of rosuvastatin. The key step is Wittig coupling of (2S,4R)-4-(tert-butyldimethylsilyloxy)-6-oxotetrahydro-2H-pyran-2-carbaldehyde and phosphonium salt of an appropriately functionalized pyrimidine heterocycle. One-pot deprotection and hydrolysis of the resulting 4-O-TBS rosuvastatin lactone provided rosuvastatin in high yield.
Casar
Zdenko
Z
Lek Pharmaceuticals, d.d., Sandoz Development Center Slovenia, API Development, Organic Synthesis Department, Kolodvorska 27, 1234 Menges, Slovenia. zdenko.casar@sandoz.com
Steinbücher
Miha
M
Kosmrlj
Janez
J
D005464:Fluorobenzenes / Q000138:chemical synthesis* / Q000737:chemistry; D007783:Lactones / Q000737:chemistry*; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry; D000068718:Rosuvastatin Calcium; D013237:Stereoisomerism; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry
D005464:Fluorobenzenes; D007783:Lactones; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium