Enantioselective synthesis of (R)-(+)- and (S)-(-)-higenamine and their analogues with effects on platelet aggregation and experimental animal model of disseminated intravascular coagulation |
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| Authors: | Pyo Mi Kyung Lee Duck-Hyung Kim Doo-Hyun Lee Ji-Hye Moon Jong-Cheon Chang Ki Churl Yun-Choi Hye Sook |
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| Institution: | aNatural Product Research Institute, College of Pharmacy, Seoul National University, Yeongeon-dong 28, Jongro-gu, Seoul 110-460, Republic of Korea;bDepartment of Chemistry, Sogang University, Shinsoo-dong 1, Mapo-gu, Seoul 121-742, Republic of Korea;cDepartment of Pharmacology, School of Medicine, Institute of Health Sciences and Gyeongsang National University, 92 Chilamdong, Jinju 660-751, Republic of Korea |
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| Abstract: | Optically active tetrahydroisoquinoline alkaloids, (R)-(+)-higenamine (1R) and (S)-(−)-higenamine (1 S), and their optically active 1-naphthylmethyl analogues (2 and 3), were synthesized by enantioselective hydrogenation of the corresponding dihydroisoquinoline intermediates 7 as a key step. The evaluation of the platelet anti-aggregation effect demonstrated clearly that the (S)-(−)-enantiomers, 1S, 2S, and 3S, had higher inhibitory potency than the corresponding (R)-(+)-antipodes, 1R, 2R, and 3R, respectively, to platelet aggregation induced by epinephrine. 1S enantiomer was superior to the corresponding 1R enantiomer in attenuating all of the disseminated intravascular coagulation (DIC) and multiple organ failure (MOF) parameters tested, while the S enantiomers 2S and 3S ameliorated some of the DIC and MOF parameters more effectively than the corresponding antipodes 2R and 3R. |
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| Keywords: | Enantioselective synthesis (R)-(+)- and (S)-(− )-higenamine Platelet aggregation Disseminated intravascular coagulation (DIC) Multiple organ failure (MOF) |
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