Protecting-group-free total synthesis of isoquinoline alkaloids by nickel-catalyzed annulation of o-halobenzaldimine with an alkyne as the key step.

Abstract

An efficient short total synthesis of benzo[c]phenanthridine alkaloids including oxyavicine, oxynitidine, and oxysanguinarine is described. Thus, N-methyl-o-bromobenzaldimines 1 b-d undergo regioselective cyclization with 4-(benzo[d][1,3]dioxol-5-yl)but-3-yn-1-ol (2 b) in the presence of [Ni(cod)(2)] (cod=1,5-cyclooctadiene). In situ oxidation of the resultant isoquinolinium salts gives isoquinolinone derivatives 5 b-d with benzo[d][1,3]dioxol-5-yl substitution at the C(3) atom and a (CH(2))(2)OH group at the C(4) atom. Later, oxidation of the alcohol group in 5 b-d to the aldehyde moiety followed by acid-catalyzed cyclization and dehydration completes the total syntheses to give oxyavicine, oxynitidine, and oxysanguinarine in 67, 65, and 60 % yields, respectively. The synthesis requires four steps from o-bromobenzaldehyde derivatives. Transformations of these alkaloids to the other alkaloids in this family are also discussed herein.

• Authors: Rajendra Prasad Korivi, Chien-Hong Cheng
• Journal: Chemistry (Weinheim an der Bergstrasse, Germany) (Chemistry) Vol. 16 Issue 1 Pg. 282-7 (Jan 04 2010) ISSN: 1521-3765 [Electronic] Germany
• PMID: 19904781 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkaloids
• Alkynes
• Hydrocarbons, Halogenated
• Imines
• Isoquinolines
• Nickel

Topics

• Alkaloids (chemical synthesis, chemistry)
• Alkynes (chemistry)
• Catalysis
• Crystallography, X-Ray
• Cyclization
• Hydrocarbons, Halogenated (chemistry)
• Imines (chemistry)
• Isoquinolines (chemical synthesis, chemistry)
• Nickel (chemistry)
• Oxidation-Reduction
• Stereoisomerism
• Structure-Activity Relationship