Method for the production of statins
Assigneeratiopharm GmbH
InventorsVitali Tararov, Armin Boerner, Gerd Koenig, Andrei Korostylev
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Abstract
The present invention relates to a process for the production of statins, which are known as HMG-CoA reductase inhibitors. A few of the intermediate compounds for use in the process in accordance with the invention are novel compounds and the invention also relates to these novel intermediate compounds.
Claims25
A process for the production of a statin comprising one of the following steps:
- a) reducing a compound of formula II:
- wherein,
- S1 is hydrogen or a hydroxyl protective group,
- S2 and S3 are independently hydroxyl protective groups, and
- R1 is hydrogen or a carboxyl protective group,
- to yield a compound of formula VI:
- or
- b) lactonizing a compound of formula II:
- wherein S1, S2, S3, and R1 are as defined above, and subsequently reducing the lactone to yield a compound of formula I-a:
- wherein S4 is a hydrogen or a hydroxyl protective group.
A process for producing a compound of formula II:
- wherein:
- S1 is hydrogen or a hydroxyl protective group,
- S2 and S3 are independently hydroxyl protective groups, and
- R1 is hydrogen or a carboxyl protective group,
- comprising the steps of:
- hydrogenating a compound of formula III:
- in the presence of catalyst (R)—Ru(TolBINAP)Cl2×AcONa, and
- optionally introducing a hydroxyl protective group.
A process for producing a compound of formula I-a:
- wherein S1 is hydrogen or a hydroxyl protective group and S4 is hydrogen or a hydroxyl protective group, comprising the steps of:
- lactolizing a compound of formula VI:
- wherein
- S1 is hydrogen or a hydroxyl protective group, and
- S2 and S3 are independently hydroxyl protective groups.
A compound of formula:
A compound of formula:
A compound of formula:
A compound of formula:
A compound of formula:
A compound of formula:
- wherein R7 is —OR8, —NR9R10, or halogen, and R8, R9, and R10 are independently hydrogen or a straight-chain, branched and/or cyclic, saturated or unsaturated C1-10 alkyl group or aryl group, wherein the C1-10 alkyl group or aryl group being optionally substituted with 1-3 optionally protected hydroxy- or carboxy groups, 1-3 alkoxy groups, 1-3 alkylamino groups and/or 1-3 halogen atoms, wherein the C1-10 alkyl group optionally contains 1-3 oxygen atoms, and/or 1-3 nitrogen atoms and wherein the C1-10 alkyl group optionally contains 1 or 2 aryl groups or is substituted by them.
Dependencies are inferred from the claim text.