Asymmetric total synthesis of (S)-isocorydine

The asymmetric total synthesis of (S)-isocorydine, a potential drug for the cure of hepatocellular carcinoma, is described. Asymmetric transfer hydrogenation of 3,4-dihydroisoquinoline using a chiral Ru(II) catalyst was applied to the synthesis of isocorydine as the key step, in which the ee value achieved is up to 99%. The overall yield is 9.4% after 12 synthetic procedures.

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(S)-1-(3-Benzyloxy-2-bromo-4-methoxy)benzyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolineC26H28BrNO4Ee >99%[α]D24 = +63.0 (c 1.12, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-1-(3-Benzyloxy-2-bromo-4-methoxy)benzyl-6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinloineC27H30BrNO4[α]D24 = +70.0 (c 1.03, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-11-Benzyloxy-5,6,6a,7-tetrahydro-1,2,10-trimethoxy-6-methyl-4H-dibenzo[de,g]quinolineC27H29NO4[α]D24 = +190 (c 1.02, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-IsocorydineC20H23NO4[α]D24 = +200.0 (c 1.05, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (S)