Nitriloxy derivatives of (R) and (S)-carnitine
AssigneeSigma-Tau Industrie Farmaceutiche Riunite S.p.A.
InventorsOreste Piccolo, Roberto Castagnani, Paolo De Witt
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Abstract
Carnitine derivatives of formula (I) are described in racemic and/or optically active form, as well as the process for their preparation and their use as pharmaceutical anti-angina active ingredients for the treatment of ischaemic heart disease. Also described is a process for producing the (R)-carnitine enantiomer from (S)-carnitine (or vice versa), using the derivatives of formula (I).
Claims13
A process for the preparation of a compound of formula (I) in optically active form with absolute configuration (S)
- where
- Y is OH;
- X− is NO3−
- or a compound of formula (I) in the form of an inner salt of the formula (II)
- and their enantiomerically enriched mixtures, comprising treating a formula (III) compound with a nitrating agent not involving the formation of a bond with the asymmetric carbon atom according to the following scheme:
- where T is an hydroxy group, X1−, equal to or different from X− to yield the formula (I) compound with the same absolute configuration as the formula (III) compound.
A process for the preparation of (R)-carnitine starting from the corresponding enantiomer (S) of a compound
- of formula (I) in optically active form with absolute configuration (S)
- where
- Y is OH;
- X− is NO3−
- or a compound of formula (I) in the form of an inner salt of the formula (II)
- and their enantiomerically enriched mixtures comprising treating said compound with a diluted base.
A process for the preparation of (R)-carnitine from (S)-carnitine comprising transformation of the formula (I) compound
- in which Y═OR or NR1R2, with R═H, C1-C10 alkyl, or substituted alkyl and where R1R2, equal or different from one another, are hydrogen, C1-C10 alkyl and X−═NO3−, into the formula (IV) compound, enantiomerically enriched of, respectively, absolute configuration (R):
- with organic or inorganic bases in water or water and organic solvent mixable with water.
Dependencies are inferred from the claim text.