A stereoselective synthesis of (2S,3R)-β-methoxyphenylalanine: a component of cyclomarin A

A stereoselective synthesis of (2S,3R)-β-methoxyphenylalanine, an amino acid contained within the cyclic peptide cyclomarin A, was successfully synthesized from Lajoie’s serine aldehyde.

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Benzyl-(1S,2R)-2-hydroxy-1-(4′-methyl-2′,6′,7′-trioxabicyclo[2.2.2]octan-1′-yl)-2-phenylethylcarbamateC22H25NO6Ee >95%[α]D20=-35.3 (c 0.75, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2R)

Benzyl-(1S,2R)-2-methoxy-1-(4′-methyl-2′,6′,7′-trioxabicyclo[2.2.2]octan-1′-yl)-2-phenylethylcarbamateC23H27NO6Ee >95%[α]D20=-15.0 (c 0.93, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2R)

(1S,2R)-2-Methoxy-1-(4′-methyl-2′,6′,7′-trioxabicyclo[2.2.2]octan-1′-yl)-2-phenylethanamineC15H21NO4Ee >95%[α]D20=-16.80 (c 1.47, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2R)

(2S,3R)-2-Amino-3-methoxy-3-phenylpropanoic acidC10H13NO3Ee >95%[α]D20=-18.4 (c 0.40, H2O)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R)

(S)-Benzyl-1-(4′-methyl-2′,6′,7′-trioxabicyclo[2.2.2]octan-1′-yl)-2-oxo-2-phenylethyl-carbamateC22H23NO6Ee >95%[α]D20=-14.1 (c 0.40, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S)

Benzyl-(1S,2S)-2-hydroxy-1-(4′-methyl-2′,6′,7′-trioxabicyclo[2.2.2]octan-1′-yl)-2-phenylethylcarbamateC22H25NO6Ee >95%[α]D20=-15.5 (c 0.70, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2S)

Benzyl-(1S,2S)-2-methoxy-1-(4′-methyl-2′,6′,7′-trioxabicyclo[2.2.2]octan-1′-yl)-2-phenylethylcarbamateC23H27NO6Ee >95%[α]D20=-7.2 (c 0.61, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2S)

(1S,2S)-2-Methoxy-1-(4′-methyl-2′,6′,7′-trioxabicyclo[2.2.2]octan-1′-yl)-2-phenylethanamineC15H21NO4Ee >95%[α]D20=-6.5 (c 1.10, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2S)

(2S,3S)-2-Amino-3-methoxy-3-phenylpropanoic acidC10H13NO3Ee >95%[α]D20=34.5 (c 0.55, H2O)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3S)

(2S,3R)-N-Cbz-β-Methoxyphenylalanine(OTMSE) esterC23H31NO5SiEe >95%[α]D20=-15.2 (c 0.70, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R)

(S)-N-Cbz-Ala-(2S,3R)-N-Cbz-β-Methoxyphenylalanine(OTMSE) esterC10H36O6N2SiEe >95%[α]D20=-12.00 (c 1.95, CHCl3)Source of chirality: asymmetric synthesis and (S)-alanineAbsolute configuration: (S), (2S,3R)

(S)-N-Cbz-Val-(S)-N-Me-Cbz-Leu(OTMSE)C25H42N2O5SiEe >95%[α]D20=-16.1 (c 0.36, CHCl3)Source of chirality: (S)-valine and (S)-leucineAbsolute configuration: (S), (S)

(2S,3R)-N-Cbz-β-Methoxyphenylalanine-(S)-Val-(S)-N-Me-Val(OTMSE) esterC35H53N3O7SiEe >95%[α]D20=-16.1 (c 0.36, CHCl3)Source of chirality: asymmetric synthesis, (S)-valine and (S)-leucineAbsolute configuration: (2S,3R), (S), (S)