The natural products chemistry of the red algae Ptilota filicina

133 Pages·2013·0.7 MB·English

by  Lopez, Albert

AN ABSTRACT OF THE THESIS OF
Albert Lopez for the degree of Master of Science in Pharmacy
presented on May 14, 1987.
Title: The Natural Products Chemistry of the Red Algae Ptilota
filicina and Laurencia obtusa
Redacted for Privacy
Abstract approved:
Dr. William H. Gerwick
The sea offers a wide variety of potentially useful
resources. Marine algae have been a rich source of structurally
unique natural products showing diverse biological properties. The
current need to develop new antifungal, antibiotic, anticancer and
antiviral drugs has prompted intense research efforts into the
discovery, isolation and structure determination of these potential
medicinal agents from seaweeds.
Over the past two years a survey of the biomedicinal
potential of seaweeds from the Oregon Coast has been conducted. In
this period we have made 125 survey collections representing some
85 different species of algae. On the basis of antimicrobial
bioassays and preliminary chemical characterization, 16 seaweeds
have been identified for further study. This research has
investigated, using standard chromatographic and spectrochemical
techniques including 2D NMR spectroscopy, the natural products of
the previously unstudied red alga Ptilota filicina J. Agardh
(order: Ceramiales).
P. filicina, which grows abundantly on rocks in the mid-
intertidal zones along the central Oregon coast, yielded a unique
series of w-3 fatty acids. Two of them were found to be
stereoisomeric icosapentaenoic acids containing conjugated triene
functionalities, while a third, ptilodene, was characterized as
another novel 20-carbon fatty acid with oxidation sites at C-11 and
C-16. Ptilodene showed slight antimicrobial activity to pathogenic
gram-negative and gram-positive bacteria, and moderate inhibition
to the dog kidney Na+/K+ ATPase.
From a previous survey of marine algae from the Caribbean,
the red seaweed Laurencia obtusa (Hudson) Lamouroux (order:
Ceramiales) was identified for further investigation. L. obtusa is
a recognized source of many novel natural products and occurs
worldwide in tropical and subtropical marine habitats. Of the
several collections made, the Isleta Marina collection
(northeastern coast of Puerto Rico) was shown to possess two novel
isomeric brominated sesquiterpenes, in addition to the previously
known sesquiterpenes, elatol and obtusol.
A minor component of this research was devoted to the
isolation of hormothamnione, the first naturally occuring
styrylchromone, from the tropical marine cyanophyte Hormothamnion
enteromorphoides Grunow. Hormothamnione was found to be a potent
cytotoxin to cancer cells in vitro and appears to be a selective
inhibitor of RNA synthesis.
The results obtained from our survey of Oregon seaweeds
contradicts the generally accepted hypothesis that temperate-cold
water algae, as versus tropical algae, are devoid of interesting
secondary metabolites. The occurrence of novel w-3 icosapentaenoic
acids is of current interest because of their structural similarity
to 5Z, 8Z, 11Z, 14Z, 17Z- icosapentaenoic acid, arachidonic acid
and related derivatives of these, many of which possess significant
hormonal and bioregulatory functions in mammalian systems.
The Natural Products Chemistry of the
Red Algae Ptilota filicina and Laurencia obtusa
by
Albert Lopez
A THESIS
submitted to
Oregon State University
in partial fulfillment of
the requirements for the
degree of
Master of Science
Completed May 14, 1987
Commencement June 1988
APPROVED:
Redacted for Privacy
Professor of Pharmacy in charge of m\-a...j.'or
Redacted for Privacy
Dean of'Colleie of Pharmacy
Redacted for Privacy
Dean of Graduat chool A
(1'
Date thesis is presented May 14, 1987
Typed by researcher for Albert Lopez
ACKNOWLEDGEMENTS
I am extremely grateful to my advisor Dr. William H. Gerwick
for his friendliness, patience, support and assistance throughout
my graduate studies. His constant guidance and encouragements
stimulated my curiosity as well as my desire to do research.
I would like to thank my committee members, Dr. George C.
Constantine and Dr. Stephen J. Gould for their valuable advice and
assistance.
I acknowledge the Oregon State Sea Grant Program and the
College of Pharmacy for their financial support during the length
of my graduate studies.
I wish to express my deepest appreciation to all my fellow
graduate students (including my friends at Chemistry), faculty,
secretarial staff and stockroom manager of Pharmacy for their help
and friendship.
I am deeply grateful to my parents, brothers and sister for
their love, financial support and for believing in me.
My special thanks to my darling Lorraine (Mi Prieta) for her
patience, devotion, faith and love. Even though we were separated
for hundreds and hundreds of miles, she always managed to be close
to my heart.
TABLE OF CONTENTS
CHAPTER I: GENERAL INTRODUCTION
1
CHAPTER II: A SURVEY OF THE BIOMEDICINAL POTENTIAL 25
OF SEAWEEDS FROM THE OREGON COAST
ABSTRACT 25
INTRODUCTION 26
MATERIALS AND METHODS 28
RESULTS AND DISCUSSION 32
CONCLUSIONS 34
CHAPTER III. TWO NEW ICOSAPENTAENOIC ACIDS FROM THE 59
TEMPERATE RED SEAWEED PTILOTA FILICINA
J. AGARDH
ABSTRACT 59
INTRODUCTION 60
EXPERIMENTAL 62
RESULTS AND DISCUSSION 65
CHAPTER IV. PTILODENE, A NOVEL EICOSANOID NA+/K+ ATPASE 77
INHIBITOR FROM THE MARINE ALGA PTILOTA
FILICINA J. AGARDH
ABSTRACT 77
INTRODUCTION 78
EXPERIMENTAL 80
RESULTS AND DISCUSSION 83
CHAPTER V TWO NEW CHAMIGRENE SESQUITERPENOIDS FROM THE 90
RED ALGA LAURENCIA OBTUSA (HUDSON) LAMOUROUX
ABSTRACT 90
INTRODUCTION 91
EXPERIMENTAL 92
RESULTS AND DISCUSSION 95
BIBLIOGRAPHY 101
APPENDIX 112
LIST OF FIGURES
Figure Page
I.1 Taxonomic classification of Ptilota filicina 16
J. Agardh.
1.2 Taxonomic classification of Laurencia obtusa 17
(Hudson) Lamouroux.
1.3 Sesquiterpenoids isolated from L.obtusa. 18
1.4 Diterpenoids isolated from L. obtusa. 21
1.5 Triterpenoids isolated from L. obtusa. 22
1.6 C-15 acetogenins isolated from L obtusa. 23
11.1 Generalized extraction scheme. 35
III.1 Chemical structures of the isolated P. filicina 70
metabolites (1) and (3), together with their
respective methyl ester derivatives.
111.2 1H-1H COSY of methyl 5(Z),7(E),9(E),14(Z), 71
17(Z)-icosapentaenoate (2) showing correlations
between coupled protons (ca. 7 mg of 2 in 0.4 ml
CDC13 with 0.3% TMS, 5 mm tube, 400, MHz).
111.3 1H-13C HETCOR of methyl 5(E),7(E),9(E),14(Z), 72
17(Z)-icosapentaenoate (4) showing one bond
coupling (1J) correlation between carbons and their
respective protons (ca. 20 mg of 4 in 0.4 ml CDC13
with 0.3% TMS, 5 mm tube; IH NMR at 400 MHz,
13C NMR at 100 MHz).
111.4 Proposed biogenesis of conjugated triene fatty 73
acids of P. filicina.
IV.1 The chemical structures of ptilodene (6) and its 86
acetate-methyl ester derivative (7).
IV.2 1H-1H COSY of acetate-methyl ester derivative (7) 87
showing one bond coupling (IJ) correlation between
carbons and their respective protons.
IV.3 Proposed biogenesis for ptilodene (6). 88
V.1 Chemical structures of obtusadiene (8) and 97
isoobtusadiene (9) isolated from L. obtusa
and of the p-Br benzoate derivative (10).
V.2 Proposed biogenesis of natural products 98
(8) and (9).
A.1 Chemical structures of hormothamnione (11) and 118
its triacetate derivative (12).
A.2 A computer generated perspective drawing of the 119
final x-ray model of hormothamnione triacetate
(12).The chromone fragment (atoms 01 to C8a) is
planar, and the substituents on the fully
substituted aromatic ring are all rotated out of
the plane. The relevant torsional angles vary
from 50° for C8-C7-031-C21 to 87° for C7-C8-032-C22.
The acetate substituents on the 1,3,5,- substituted
ring are also rotated by roughly 77°.