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The synthesis and biological activity of two analogs of the anti‐HIV alkaloid michellamine B
Author(s) -
Upender Velaparthi,
Pollart Daniel J.,
Liu Jyanwei,
Hobbs Peter D.,
Olsen Cris,
Chao WanRu,
Bowden Bonnie,
Crase Jac L.,
Thomas David W.,
Pandey Anjali,
Lawson John A.,
Dawson Marcia I.
Publication year - 1996
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570330460
Subject(s) - chemistry , alkaloid , stereochemistry , tetrahydroisoquinoline , recombinant dna , human immunodeficiency virus (hiv) , biological activity , in vitro , biochemistry , virology , biology , gene
Two simplified analogs of the dimeric naphthalenyltetrahydroisoquinoline alkaloid michellamine B [4′,4″‐didesmethoxy‐2′,2″‐didesmethylmichellamine B and 6,8‐dihydroxy‐5‐(1′,1″‐dihydroxy‐2′,2″‐binaphthalen‐4′‐yl)‐1 R ,3 R ‐dimethyl‐1,2,3,4‐tetrahydroisoquinoline] were synthesized using Suzuki palladiumcatalyzed biaryl cross‐coupling of 4‐(2‐benzyl‐6,8‐dibenzyloxy‐1 R ,3 R ‐dimethyl‐1,2,3,4‐tetrahydroisoquinolin‐5‐yl)‐1‐benzyloxy‐2‐bromonaphthalene to its corresponding atropisomeric 2‐naphthaleneboronic acid and 1‐benzyloxy‐2‐naphthaleneboronic acid, respectively. These analogs inhibited recombinant HIV reverse transcriptase with IC 5() values of 62 μ M and 1000 μ M , respectively, whereas the IC 5() value for michellamine B was 33 μ M . Both michellamine B and the analogs inhibited the phosphorylation of histories by rat brain protein kinase C. The analogs were more active (IC 50 values of 36 μ M and 30 μ M , respectively) than michellamine B (IC 50 = 130 μ M ).