How are rosuvastatin's intermediates formed?

How are rosuvastatin's intermediates formed?

Rosuvastatin is made through a convergent synthesis that brings two fragments together. The first fragment is the chiral diol side chain, which comes from a protected form of (3R,5S)-3,5-dihydroxyhept-6-enoic acid. This is usually prepared from cheap, cheap, starting materials such as L-ascorbic acid or D-erythronolactone by a series of functional-group transformations that keep the chiral centers intact.

The second fragment is the pyrimidine core. It contains the 4-(4-fluorophenyl)-5-isopropyl-2-(N-methyl-N-methylsulfonylamino)pyrimidine ring. Core formation begins with a Biginelli-like reaction or condensation involving an 4-4-fluorophenyl-β-ketoester, an 4-4-fluorophenyl-β-ketoester, and guanidine derivatives. Condensation of 4-4-fluorphenyl-acrylonitrile with suitable reagents gives the pyrimidine ring, condensation of 4-4-fluorophenyl-acrylonitrile with suitable reagents gives the pyrimidine ring.