A concise synthesis of (R)- and (S)-α-alkyl isoserines from d- and l-malic acids

A simple and diastereoselective method for the synthesis of (R)- and (S)-α-alkyl isoserines has been developed in four steps starting from commercially available d- and l-malic acid, respectively. This approach features stereocontrolled alkylation of 2-(2-tert-butyl-5-oxo-1,3-dioxolan-4-yl)acetic acid and proceeds through a methylcarbamate via a Curtius rearrangement.

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Methyl ((2R,4R)-2-tert-butyl-4-benzyl-5-oxo-1,3-dioxolan-4-yl)carbamateC17H23NO5[α]D18=-30.0 (c 1.0, CH2Cl2)Source of chirality: d-malic acid and diastereoselective synthesisAbsolute configuration: (2R,4R)

Methyl ((2R,4R)-2-tert-butyl-4-ethyl-5-oxo-1,3-dioxolan-4-yl)carbamateC12H21NO5[α]D18=-18.1 (c 1.0, CH2Cl2)Source of chirality: d-malic acid and diastereoselective synthesisAbsolute configuration: (2R,4R)

Methyl ((2R,4R)-2-tert-butyl-4-allyl-5-oxo-1,3-dioxolan-4-yl)carbamateC13H21NO5[α]D18=-26.0 (c 1.3, CH2Cl2)Source of chirality: d-malic acid and diastereoselective synthesisAbsolute configuration: (2R,4R)

Methyl ((2R,4R)-2-tert-butyl-4-methyl-5-oxo-1,3-dioxolan-4-yl)carbamateC11H19NO5[α]D18=-9.3 (c 1.1, CH2Cl2)Source of chirality: d-malic acid and diastereoselective synthesisAbsolute configuration: (2R,4R)

Azido-N-((2R,4R)-4-benzyl-2-tert-butyl-5-oxo-1,3-dioxolan-4-yl)formamideC16H20N4O4[α]D18=-24.0 (c 1.0, CH2Cl2)Source of chirality: d-malic acid and diastereoselective synthesisAbsolute configuration: (2R,4R)

(R)-3-Amino-2-benzyl-2-hydroxypropanoic acidC10H13NO3[α]D18=-53.0(c 0.45, H2O)Source of chirality: d-malic acid and diastereoselective synthesisAbsolute configuration: (R)

(R)-2-(Aminomethyl)-2-hydroxybutanoic acidC5H11NO3[α]D18=-18.0 (c 1.0, H2O)Source of chirality: d-malic acid and diastereoselective synthesisAbsolute configuration: (R)

(R)-2-(Aminomethyl)-2-hydroxypent-4-enoic acidC6H11NO3[α]D18=-43.7 (c 0.50, H2O)Source of chirality: d-malic acid and diastereoselective synthesisAbsolute configuration: (R)

(R)-3-Amino-2-hydroxy-2-methylpropanoic acidC4H9NO3[α]D18=-11.5 (c 1.0, H2O)Source of chirality: d-malic acid and diastereoselective synthesisAbsolute configuration: (R)