Synthesis of crambescin B carboxylic acid, a potent inhibitor of voltage-gated sodium channels

Atsuo Nakazaki; Yuki Ishikawa; Yusuke Sawayama; Mari Yotsu-Yamashita; Toshio Nishikawa

doi:10.1039/c3ob42017e

Synthesis of crambescin B carboxylic acid, a potent inhibitor of voltage-gated sodium channels

Org Biomol Chem. 2014 Jan 7;12(1):53-6. doi: 10.1039/c3ob42017e. Epub 2013 Nov 11.

Authors

Atsuo Nakazaki¹, Yuki Ishikawa, Yusuke Sawayama, Mari Yotsu-Yamashita, Toshio Nishikawa

Affiliation

¹ Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan. nisikawa@agr.nagoya-u.ac.jp.

PMID: 24216693
DOI: 10.1039/c3ob42017e

Abstract

The stereocontrolled synthesis of a racemic carboxylic acid of crambescin B, a marine alkaloid, is described. The synthesis features two highly stereoselective reactions: (I) palladium-catalyzed hydroxymethylation of an alkynyl aziridine having an N-guanidino group and (II) cascade bromocyclization providing a spiro-hemiaminal structure. The cell-based colorimetric assay showed that the synthesized carboxylic acid exhibited a potent inhibitory activity on voltage-gated sodium channels.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carboxylic Acids / chemical synthesis
Carboxylic Acids / chemistry
Carboxylic Acids / pharmacology*
Colorimetry
Molecular Conformation
Pyrimidines / chemical synthesis
Pyrimidines / chemistry
Pyrimidines / pharmacology*
Spiro Compounds / chemical synthesis
Spiro Compounds / chemistry
Spiro Compounds / pharmacology*
Stereoisomerism
Voltage-Gated Sodium Channels / metabolism*

Substances

Carboxylic Acids
Pyrimidines
Spiro Compounds
Voltage-Gated Sodium Channels
crambescin B