Synthesis of crambescin B carboxylic acid, a potent inhibitor of voltage-gated sodium channels.
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.
Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan. nisikawa@agr.nagoya-u.ac.jp.
Atsuo
A
Nakazaki
Yuki
Y
Ishikawa
Yusuke
Y
Sawayama
Mari
M
Yotsu-Yamashita
Toshio
T
Nishikawa
D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003124:Colorimetry; D008968:Molecular Conformation; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism*
D002264:Carboxylic Acids; D011743:Pyrimidines; D013141:Spiro Compounds; D061566:Voltage-Gated Sodium Channels; C086364:crambescin B