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US 2024/0360086 A1Published application
Rosuvastatin calcium and process for producing intermediate thereof
AssigneeApi Corporation
InventorsTomoko MAEDA, Yasumasa DEKISHIMA, Hiroshi KAWABATA, Masaki NAGAHAMA, Naoyuki WATANABE, Kosuke ITO
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Abstract
An object of the present invention is to provide a novel method capable of producing rosuvastatin calcium and intermediates therefor efficiently, inexpensively and with high purity. The present invention provides a method of efficiently producing rosuvastatin calcium and intermediates therefor having a high purity at an industrial scale, without using an extremely low temperature reaction or a special asymmetric catalyst.
Claims2
A production method of rosuvastatin calcium represented by the following formula (6):
- the method comprising:
- hydrolyzing with a base a compound represented by formula (2):
- wherein R is a n-propyl group or an isopropyl group, obtained by a method comprising:
- reducing a compound represented by the following formula (1a):
- wherein R is as defined for R in said formula (2), comprising reacting the compound with an enzyme having an activity capable of stereoselectively reducing a carbonyl group, a microorganism or cell having an ability to produce the enzyme, a treated product of the microorganism or cell, and/or a culture solution containing the enzyme obtained by culturing the microorganism or cell;
- wherein said enzyme comprises a polypeptide selected from:
- (A) a carbonyl reductase (OCR1) polypeptide of SEQ ID NO:
- 2 derived from Ogataea minuta var. nonfermentans NBRC1473,
- (B) a polypeptide consisting of an amino acid sequence having a homology of 90% or more to the amino acid sequence shown in SEQ ID NO:
- 2, and having an activity to convert a compound represented by said formula (1a) to a compound represented by said formula (2), and
- (C) a polypeptide comprising an amino acid sequence which is the amino acid sequence shown in SEQ ID NO:
- 2, wherein 20 or less amino acids are substituted, deleted or added, and having an activity to convert a compound represented by said formula (1a) to a compound represented by said formula (2);
- and
- reacting the product thereof with a calcium compound.
11 more elements
A production method of rosuvastatin calcium represented by the following formula (6):
- the method comprising:
- (iia) condensing a compound represented by the following formula (3):
- and a compound represented by the following formula (4a):
- wherein R2 is a tert-butyl group, in the presence of a base to obtain a compound represented by the following formula (5):
- wherein R2 is as defined for R2 in said formula (4a);
- (iib) reacting the compound represented by formula (5) with an alcohol represented by R—OH, wherein R is a n-propyl group isopropyl group to obtain a compound represented by the following formula (1a):
- wherein R is as defined for R in said R—OH;
- and
- (iiia) hydrolyzing with a base a compound represented by the following formula (2)
- wherein R is a n-propyl group or an isopropyl group, obtained by a method comprising:
- reducing a compound represented by said formula (1a), comprising reacting the compound with an enzyme having an activity capable of stereoselectively reducing a carbonyl group, a microorganism or cell having an ability to produce the enzyme, a treated product of the microorganism or cell, and/or a culture solution containing the enzyme obtained by culturing the microorganism or cell;
- wherein said enzyme comprises a polypeptide selected from:
- (A) a carbonyl reductase (OCR1) polypeptide of SEQ ID NO:
- 2 derived from Ogataea minuta var. nonfermentans NBRC1473,
- (B) a polypeptide consisting of an amino acid sequence having a homology of 90% or more to the amino acid sequence shown in SEQ ID NO:
- 2, and having an activity to convert a compound represented by said formula (1a) to a compound represented by said formula (2), and
- (C) a polypeptide comprising an amino acid sequence which is the amino acid sequence shown in SEQ ID NO:
- 2, wherein 20 or less amino acids are substituted, deleted or added, and having an activity to convert a compound represented by said formula (1a) to a compound represented by said formula (2), and then reacting with a calcium compound.
15 more elements
Dependencies are inferred from the claim text.