title: Lactone pathway to statins utilizing the Wittig reaction. The synthesis of rosuvastatin.
abstract: 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.
authors.affiliation: Lek Pharmaceuticals, d.d., Sandoz Development Center Slovenia, API Development, Organic Synthesis Department, Kolodvorska 27, 1234 Menges, Slovenia. zdenko.casar@sandoz.com
authors.forename: Zdenko
authors.initials: Z
authors.lastname: Casar
authors.forename: Miha
authors.initials: M
authors.lastname: Steinbücher
authors.forename: Janez
authors.initials: J
authors.lastname: Kosmrlj
mesh_terms: 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
chemical_list: D005464:Fluorobenzenes; D007783:Lactones; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium