2. Academic Validation
  3. Divergent Synthesis of Natural Derivatives of (+)-Saxitoxin Including 11-Saxitoxinethanoic Acid

Divergent Synthesis of Natural Derivatives of (+)-Saxitoxin Including 11-Saxitoxinethanoic Acid

  • Angew Chem Int Ed Engl. 2019 Feb 4;58(6):1689-1693. doi: 10.1002/anie.201811717.
James R Walker 1,  Jeffrey E Merit 2,  Rhiannon Thomas-Tran 3,  Doris T Y Tang 4,  J Du Bois 4
Affiliations

Affiliations

  • 1 SAFC, Inc., 645 Science Dr., Madison, WI, 53711, USA.
  • 2 Gilead Sciences, 333 Lakeside Dr., Foster City, CA, 94404, USA.
  • 3 Arcus Biosciences, Inc., 3928 Point Eden Way, Hayward, CA, 94545, USA.
  • 4 Department of Chemistry, Stanford University, Stanford, CA, 94305, USA.
PMID: 30488599 DOI: 10.1002/anie.201811717
Abstract

The bis-guanidinium toxins are a collection of natural products that display nanomolar potency against select isoforms of eukaryotic voltage-gated Na+ ion channels. We describe a synthetic strategy that enables access to four of these poisons, namely 11-saxitoxinethanoic acid, C13-acetoxy saxitoxin, decarbamoyl saxitoxin, and saxitoxin. Highlights of this work include an unusual Mislow-Evans rearrangement and a late-stage Stille ketene acetal coupling. The IC50 value of 11-saxitoxinethanoic acid was measured against rat NaV 1.4, and found to be 17.0 nm, similar to those of the sulfated toxins gonyautoxin II and III.

Keywords

Stille coupling; guanidinium toxins; rearrangement; sodium channels; sulfoxide.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z