Fluorinated Carbohydrates. Chemical and Biochemical Aspects

222 Pages·1988·3.68 MB·English

by  N. F. TAYLOR (Eds.)

Fluorinate Carbohydrate
In Fluorinated Carbohydrates; TAYLOR, N.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1988.
In Fluorinated Carbohydrates; TAYLOR, N.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1988.
ACS SYMPOSIUM SERIES 374
Fluorinated Carbohydrates
Chemical and Biochemical Aspects
N. F. Taylor, EDITOR
University of Windsor
Developed from a symposium sponsored by
the Division of Carbohydrate Chemistry
at the 194th Meeting
of the American Chemical Society,
New Orleans, Louisiana
August 30-September 4, 1987
American Chemical Society, Washington, DC 1988
In Fluorinated Carbohydrates; TAYLOR, N.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1988.
Library of Congress Cataloging-in-Publication Data
Fluorinated carbohydrates: chemical and biochemical aspects
N.F. Taylor, editor
p. cm.(ACS Symposium Series: 374).
Developed from a symposium sponsored by the Division
of Carbohydrate Chemistry at the l94th Meeting of the
American Chemical Sociefy. Ne
August 20-September 4,1987
Includes bibliographies and
ISBN 0-8412-1492-1
1. Fluorocarbohydrates—Physiological effect-
Congresses. 2. Fluorocarbohydrates—Therapeutic use—
Testing—Congresses. 3. Fluorocarbohydrates—
Synthesis—Congresses.
I. Taylor, N. F. II. American Chemical Society.
Division of Carbohydrate Chemistry. III. Series.
QP702.F58F58 1988
547.7'.81-dcl9 88-19332
CIP
Copyright © 1988
American Chemical Society
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In Fluorinated Carbohydrates; TAYLOR, N.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1988.
ACS Symposium Series
M. Joan Comstock, Series Editor
1988 ACS Books Advisory Board
Paul S. Anderson Vincent D. McGinniss
Merck Sharp & Dohme Research Battelle Columbus Laboratories
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University of Iowa
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In Fluorinated Carbohydrates; TAYLOR, N.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1988.
Foreword
The ACS SYMPOSIUM SERIES was founded in 1974 to provide a
medium for publishing symposia quickly in book form. The
format of the Series parallels that of the continuing ADVANCES
IN CHEMISTRY SERIES except that, in order to save time, the
papers are not typeset but are reproduced as they are submitted
by the authors in camera-ready form. Papers are reviewed under
the supervision of th Editor with th assistanc f th Serie
Advisory Board and
symposia; however, verbatim reproductions of previously pub
lished papers are not accepted. Both reviews and reports of
research are acceptable, because symposia may embrace both
types of presentation.
In Fluorinated Carbohydrates; TAYLOR, N.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1988.
Preface
THE DIVERSE CHEMICAL, BIOLOGICAL, AND INDUSTRIAL APPLICATIONS
of the numerous synthetic carbon—fluorine compounds are almost
legendary. In 1944, Marais identified fluoroacetate in the leaves of the
South African shrub Dichapetalum
biologists continue to b
and properties of the C-F bond.
A Ciba Foundation symposium was first published in 1972 to honor
the contribution made by Sir Rudolph Peters to the biochemical aspects
of the subject. This book was followed in 1976 by an ACS Symposium
Series publication, Biochemistry Involving Carbon-Fluorine Bonds.
The natural occurrence of the C-F bond in carbohydrates is
restricted to nucleocidin, an antibiotic in which the hydrogen at C-4 of
this ribofuranoside is replaced by fluorine. In contrast, during the last
10 years, new synthetic methods for the introduction of both 19F and 18F
into carbohydrates have led to an explosive growth in the number and
variety of fluorinated sugars. Therefore, compounds that were relatively
rare have become readily accessible for chemical and biochemical
research.
The topics reported in this book reflect recent studies in the
synthesis, reactivity, and some biochemical aspects of fluorinated
carbohydrates. An appropriate combination of chemical and enzymatic
methods now provides a versatile approach for the stereospecific
introduction of fluorine into monosaccharides, disaccharides,
oligosaccharides, and in the future, polysaccharides. A recurrent theme
in biochemical studies is based on the rationale that 19F and 18F may
replace the hydroxyl group of carbohydrates with minimal perturbance of
molecular structure and conformation. The changes in biochemical
reactivity, combined with the specific hydrogen-bonding capacity of the
C-F bond, permit the use of deoxyfluorinated sugars as unique cellular
and enzymatic probes. Studies illustrate carbohydrate metabolism,
enzymology, antigen-antibody specificity, carbohydrate transport, and
the design of new antiviral and antitumor agents. The inhibition and
modification of viral-envelope glycoprotein synthesis by fluorinated
ix
In Fluorinated Carbohydrates; TAYLOR, N.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1988.
sugars promises to be a new approach to the interference with
virus-retrovirus-host cell membrane interactions.
The research reported in this volume raises more questions than it
answers. For this reason, the future of fluorinated carbohydrates
remains assured and many new avenues of research await further
interdisciplinary investigation. I hope the chemical and biochemical
scope of this book will continue to stimulate those already active in the
field and attract new researchers into this exciting and fascinating area of
carbohydrates.
Acknowledgments
I am deeply indebted to all contributors; without their patience and
cooperation this book would t hav bee possible I als wish t thank
Robin Giroux and the staf
and assistance when it was most needed. Finally, my thanks to Donna
Dee and Maeve Doyle for their expert secretarial and administrative
assistance. Additional financial support for the organization of the
symposium was kindly provided by E. I. du Pont de Nemours and
Company.
N. F. TAYLOR
Department of Chemistry and Biochemistry
University of Windsor
Ontario N9B 3P4, Canada
January 1988
x
In Fluorinated Carbohydrates; TAYLOR, N.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1988.
Chapter 1
Retrospect and Prospect
P. W. Kent
Nuffield Department of Clinical Biochemistry, Radcliffe Infirmary,
Oxford University, Oxford, 0X2 6HE, United Kingdom
In the past quarter of a century interest has grown apace in these
modified sugars, both i
biological potentialitie
only touch on a few of the developments which have brought us to
our present state of knowledge. For the most part, attention is
devoted to monosaccharides containing a single F atom though
undoubtedly others in which -CF and -CF have been introduced are
3 2
both interesting and potentially important.
It was evident to early workers in the field that such F
-sugars should be capable of existence if only on the grounds of the
similarity of the F-atom to the OH group in size, electronegativity
and ability to participate in H-bonded structures. Interest was
further fuelled by the discovery of the high toxicity of monofluoro-
acetate and by the bizarre fact that this compound occurred in
Nature in many plants.
An extensive series of reviews of fluorinated biological
analogues including F-carbohydrates was published in 1972 in the
form of a CIBA Symposium volume (1) and an ACS Symposium in 1976 (2).
A substantial, useful source book cataloguing properties of carbo
hydrate derivatives, including some fluorosugars has recently been
published by Collins (3).
For brevity, F-sugar denotes a deoxyfluorocarbohydrate, eg. 6F-
glucose denotes 6-deoxy-6-fluoro-D-glucose. This system is used
throughout this chapter.
RETROSPECT
Like many other areas of organic chemistry, fluorocarbohydrates had
small beginnings. The first tenuous tests seem to have been
carried out by Moissan (£) himself, the discoverer of elemental
fluorine. In his monumental monograph 'Fluor et ses Composes*
published 1900, he wrote of the reaction between F and glucose:
2
"Rien a froid: chauffe legerment, i l est attaque par
le fluor avec depot de charbon. Lorsque la temperature
s'eleve par suite de la reaction, la destruction devient
0097H5156/88/0374-0001$06.00/0
° 1988 American Chemical Society
In Fluorinated Carbohydrates; TAYLOR, N.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1988.
2 FLUORINATED CARBOHYDRATES: CHEMICAL AND BIOCHEMICAL ASPECTS
rapide et complete avec le fluoreuse de carbone et d'acide
fluorhydrique."
Sucrose and mannitol fared no better.
In the period to 1939, the limited means of synthesis led to a
slow accumulation of knowledge about fluoro-organic compounds and
their reactivity [a number of reviews of this earlier work were
published (5)]. Research in Poland, Belgium and Germany, in
particular, opened the way to further investigations. In the carbo
hydrate field, the most interesting findings were of the synthesis
and use of glycosyl fluorides with F at Cl, which could be easily
obtained by exchange reactions with metallic fluorides or by the
action of liquid HF on fully acetylated monosaccharides. Results in
this field have been reviewed by Micheel and Klemer (6). These
derivatives provided a useful protecting group for Cl, stable in
alkaline conditions but readily removable by dilute acids.
A curious finding mad
glucose from wood reveale
anhydrous HF to give glucosyl fluoride in high yield. If traces of
moisture were present, this product was not obtained and instead a
non-linear glucan, 'cellan', resulted (7). This was a random
structure, a highly branched polysaccharide in which several types
of interglycosidic linkages were present (8) . Glucose itself could
be induced to polymerise in a variety of dehydrating acidic
conditions (eg. reference 9) to give a synthetic polysaccharide
with potential as a blood plasma extender.
During the period of World War II, much research was undertaken,
results of which were not published until 1947 and after, owing to
questions of national security. In particular studies were made of
fluorophosphidates [reviewed by Saunders (10)] and of derivatives of
fluoroacetic acid and its higher homologues [reviewed by Pattison
uin.
The discovery in 1943 by Marais (12) that potassium fluoro-
acetate was the toxic material present in a number of South African
plants attracted notable attention, though the reasons for the
toxicity were not then known. Further exploration showed the
presence of the similarly toxic co-fluorooleic acid in other plants.
At that time, the techniques for quantitative microanalysis of
organic fluorides were quite inadequate until an outstanding
complexometric method was devised in Belcher's laboratory (13). It
appeared from extensive surveys that fluorofatty acids in fact were
widespread in trace quantities in many species of green plants.
The biochemical mechanism of the toxicity of fluoroacetate in
mammals was first elucidated by the notable researches of the late
Sir Rudolph Peters, who showed that in liver and kidney, the compound
was metabolically transformed into an even more toxic fluorocitric
acid isomer, a powerful inhibitor of the tricarboxylic acid cycle.
These results together with those of others, Liebecq, Bergmann,
Buffa, Gal, to name but a few, established beyond doubt this new
biochemical twist in which a potential toxic agent could be trans
formed by an existing enzyme pathway into another of greater
toxicity creating a physiologically critical situation, a phenomenon
termed "Lethal Synthesis" by Peters.
With this in mind, it was even more challenging to pursue F-
carbohydrates to see whether these would be metabolised to yield
In Fluorinated Carbohydrates; TAYLOR, N.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1988.