55527-85-0

Upstream product

• 885054-30-8 ethyl (2S,3R)-2-amino-3-methyl-4-oxopentanoate 
• 790701-97-2 ethyl (2S,3R)-2-((4-methoxyphenyl)amino)-3-methyl-4-oxopentanoate 
• 409113-02-6 (2S,3S)-ethyl 2-(p-methoxyphenylamino)-3-methyl-4-oxo-pentanoate 

Downstream Products

• 55399-93-4 (2S,3R,4S)-4-hydroxyisoleucine 
• 55399-92-3 (2S,3R,4R)-2-amino-4-hydroxy-3-methyl-pentanoic acid 

Relevant academic research and scientific papers

A practical and efficient total synthesis of potent insulinotropic (2S,3R,4S)-4-Hydroxyisoleucine through a chiral N-protected γ-keto- α-aminoester

(2S,3R,4S)-4-Hydroxyisoleucine, which exhibits remarkable insulinotropic activity, is expected to be a potent drug to treat type II diabetes. We propose herein a four-step synthesis of the enantiopure natural product on the basis of successive Mannich condensation, catalytic epimerization, N-paramethoxyphenyl deprotection, and diastereoselective reduction. This compact economical and scalable sequence enables to perfectly control three contiguous chiral centers. It does not involve any chromatographic purification, and the desired compound is obtained in >99 % de, >99 % ee, and 22 % overall yield under our optimized conditions.

Method for the synthesis of 4-hydroxyisoleucine and the derivatives thereof

The invention relates to a method for the synthesis of two isomers, at function OH, alone or in mixtures, of amino acids α or the derivatives thereof, having general formula (B), wherein: linkage C—O of the 4-position carbon (represented by symbol) denotes one or other of isomers III or IV, or mixtures thereof. Moreover, R1 and R2 represent: a hydrogen atom; or either R1 or R2 represents a hydrogen atom and the other substituent is a radical Ra, an acyl group —CORa, such as acetyl, or a functional group —COORa, —SO2Ra, —N (Ra, Rb), Ra and Rb, which are identical or different, representing a C1-C12 linear or branched alkyl radical, optionally substituted, an aryl group with one or more aromatic rings and heterocycles, comprising between 5 and 8C, optionally substituted, or aralkyl, the alkyl substituent and the aryl group being as defined above; or R1 and R2 both represent a substituent as defined above. R3 represents a hydrogen atom or Ra and R4 has the significance of Ra. The invention is characterised in that it comprises: the isomerisation of a compound having formula (I), wherein R1, R2, Ra, R3 and R4 are as defined above, such as to produce a compound having formula (II); and the reduction of the carbonyl function thereof which, depending on the catalytic system employed and the formula (I) compound used, produces one of the isomers having general formula (III) or (IV) or a mixture thereof having formula (B). The invention can be used for the synthesis of (2S, 3R, 4S)-4-hydroxyisoleucine.

DIASTEREOISOMERS OF 4-HYDROXYISOLEUCINE AND USES THEREOF

The invention relates to configurational isomers 4-hydroxyisoleucine, and to lactones, pharmaceutically acceptable salts, and prodrugs thereof, to processes for their preparation, and to pharmaceutical compositions comprising the same. The isomers of the invention exhibit insulinotropic activity and thus may be useful for the prevention and treatment of disorders of carbohydrate or lipid metabolism, including diabetes mellitus (type 1 and type 2 diabetes), pre-diabetes, and Metabolic Syndrome.

Method for preparing diastereoisomers of 4-hydroxy isoleucine

The invention relates to a method for preparing diastereoisomers of 4-hydroxy isoleucine of formula A ????????CO2H- CH(NH2)- CH(CH3)-CH(OH)-CH3?????(A) which comprises the following steps: deprotection of amine of Formula B reduction and subsequent lactonisation of an intermediate amine derivative of formula C whose substituents at positions 2 and 3 are either R, S or S, S ; or S, R or R, R,hydrolysis of the resulting lactone of formula D where in substituents at positions 2, 3 and 4 are S,R,S or S,R,R when using a protected amine S,RS,S,S or S,S,R when using a protected amine S,SR,S,R or R,S,S, when using a protected amine R,SR,R,R or R,R,S when using a protected amine R,R under conditions to obtain the desired isomer of 4-hydroxy isoleucine. Application for preparing the 8 isomeric forms of 4-hydroxy isoleucine.

Compounds and compositions for use in the prevention and treatment of obesity and related syndromes

The invention relates to 4-hydroxyisoleucine, isomers, analogs, lactones, salts, and prodrugs thereof, to processes for their preparation, and to pharmaceutical compositions comprising the same. More particularly, the invention relates to the use of those compounds in the prevention and treatment of obesity and related syndromes.