A Synthesis of Exiguaquinol Dessulfate

A concise and stereoselective synthesis of exiguaquinol dessulfate is described. Sequential application of a Diels–Alder cycloaddition, a desymmetrizing aldol addition, and a reductive Heck cyclization established most of the architecture of exiguaquinol, and a carefully choreographed introduction o...

Full description

Saved in:
Bibliographic Details
Published in:Chemistry : a European journal Vol. 22; no. 50; pp. 17953 - 17957
Main Authors: Schwarzwalder, Gregg M., Scott, David R., Vanderwal, Christopher D.
Format: Journal Article
Language:English
Published: WEINHEIM Blackwell Publishing Ltd 12.12.2016
Wiley
Wiley Subscription Services, Inc
Subjects:
Aldehydes
Aldehydes - chemistry
antibiotics
Architecture
Chemistry
Chemistry, Multidisciplinary
Congeners
Culture
Cyclization
Cycloaddition Reaction
epimers
Forges
Heck cyclization
Hydrogen bonding
Hydroquinones - chemical synthesis
Hydroquinones - chemistry
Molecular Structure
natural product synthesis
Physical Sciences
Science & Technology
Strategy
sulfation
Synthesis
CORE
SELECTIVE ANTIBACTERIAL AGENTS
PYLORI GLUTAMATE RACEMASE
natural product synthesis
MARINE SPONGE
3,6-DIMETHOXYBENZOCYCLOBUTENONE
PYRIDODIAZEPINE AMINES
GASTRIC-CANCER
Heck cyclization
epimers
sulfation
INHIBITORS
antibiotics
HELICOBACTER-PYLORI
ALKALOID JAMTINE
ISSN:0947-6539, 1521-3765, 1521-3765
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A concise and stereoselective synthesis of exiguaquinol dessulfate is described. Sequential application of a Diels–Alder cycloaddition, a desymmetrizing aldol addition, and a reductive Heck cyclization established most of the architecture of exiguaquinol, and a carefully choreographed introduction of the polar substituents afforded the title compound; unfortunately, naphthoquinol sulfation could not be achieved to deliver exiguaquinol. Our hypothesis regarding the configurational preference of the N‐acyl hemiaminal, which was based upon an analysis of internal hydrogen‐bonding interactions with polar functional groups, was proven correct. A late‐stage intermediate did not demonstrate bactericidal activity against H. pylori cultures. A desymmetrization strategy led to the synthesis of a congener of exiguaquinol, an inhibitor of the H. pylori MurI enzyme and a potential antibiotic. The pentacyclic architecture was accessed through convergent Diels–Alder and aldol additions, followed by a reductive Heck cyclization to forge the vicinal quaternary stereogenic centers.
Bibliography:istex:46151A4580FE3EE8F2EF1C8E75ACC6A29BCEDF33
ArticleID:CHEM201604506
ark:/67375/WNG-1D97VSKG-C
NIH RePORTER
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ISSN:0947-6539
1521-3765
1521-3765
DOI:10.1002/chem.201604506