Method for producing o-substituted serine derivative
AssigneeChugai Seiyaku Kabushiki Kaisha
InventorKeisuke NOGI
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Abstract
An object is to provide a method for producing an O-substituted serine derivative, in which the O-substituted serine derivative can be obtained in a small number of steps. The present inventors have intensively studied the reductive hydrogenation of cyclic N,O-acetals and found a short-step method for producing an O-substituted serine derivative with excellent positional selectivity and chemical yield while maintaining the optical purity.
Claims16
A method for producing a compound represented by the following formula (1) or a salt thereof or a solvate thereof, the method comprising the step of:
- (A) reacting a compound represented by the following formula (2) with a reducing agent to obtain a compound represented by the following formula (1):
- wherein
- R1 is an electron withdrawal group, an amino acid residue, or a peptide residue;
- (i) R2 and R3 are each independently selected from the group consisting of hydrogen, C1-C6 alkyl optionally having a substituent, C3-C6 cycloalkyl optionally having a substituent, C2-C6 alkenyl optionally having a substituent, C2-C6 alkynyl optionally having a substituent, aralkyl optionally having a substituent, aryl optionally having a substituent, and heteroaryl optionally having a substituent, or (ii) R2 and R3 together with an intervening carbon atom form a 3- to 8-membered alicyclic ring or a 4- to 7-membered saturated heterocycle;
- (i) R4 and R5 are each independently selected from the group consisting of hydrogen, C1-C6 alkyl optionally having a substituent, C3-C6 cycloalkyl optionally having a substituent, C2-C6 alkenyl optionally having a substituent, C2-C6 alkynyl optionally having a substituent, aralkyl optionally having a substituent, aryl optionally having a substituent, and heteroaryl optionally having a substituent, or (ii) R4 and R5 together with an intervening carbon atom form a 3- to 8-membered alicyclic ring or a 4- to 7-membered saturated heterocycle;
- R6 is hydrogen, C1-C6 alkyl optionally having a substituent, or aralkyl optionally having a substituent;
- R7 is —OR8, —NR9R9′, an amino acid residue, or a peptide residue;
- R8, R9 and R9′, are each independently hydrogen, C1-C6 alkyl optionally having a substituent, or aralkyl optionally having a substituent, or R9 and R9′, together with an intervening nitrogen atom form a 4- to 7-membered saturated heterocycle;
- L1 is a single bond or —CH2—;
- L2 is a single bond or —CH2—;
- L3 is a single bond or —CH2—;
- provided that when L1 is —CH2—, L2 is a single bond;
- when L2 is —CH2—, L1 and L3 each are a single bond;
- and when L3 is —CH2—, L2 is single bond.
A compound selected from the group consisting of:
- 2-(benzyloxycarbonylamino)-3-(cyclobutoxy)propanoic acid;
- 2-(benzyloxycarbonylamino)-3-isopentyloxy-propanoic acid;
- 2-(benzyloxycarbonylamino)-3-isopropoxy-butanoic acid;
- 2-[benzyloxycarbonyl(methyl)amino]-3-(cyclobutoxy)propanoic acid;
- 3-benzyloxycarbonyl-2-ethyl-oxazolidine-4-carboxylic acid;
- 3-benzyloxycarbonyl-2-isobutyl-oxazolidine-4-carboxylic acid;
- benzyl 4-(cyclobutoxymethyl)-5-oxo-oxazolidine-3-carboxylate;
- benzyl 4-{[1-methoxy-1-oxapropan-2-yl]carbamoyl}-2,2,5-trimethyloxazolidine-3-carboxylate;
- N-(benzyloxy)carbonyl-O-isopropyl-threonyl-alanine methyl ester;
- and
- N-[(9H-fluoren-9-ylmethoxycarbonyl)-leucyl]-O-isopropyl-threonine;
- or a salt thereof or a solvate thereof.
Dependencies are inferred from the claim text.