Natural Products Chemistry III

368 Pages·1988·18.421 MB·English

by  A. I. Scott (auth.), Prof. Dr. Atta-ur-Rahman, Prof. Dr. Philip William Le Quesne (eds.)

Atta-ur-Rahman . P. W. Le Quesne (Eds.)
Natural Products
Chemistryill
With 104 Figures and 86 Schemes
Springer- Verlag
Berlin Heidelberg New York
London Paris Tokyo
Prof. Dr. AnA-uR-RAHMAN
HEJ Research Institute of Chemistry
University of Karachi
Karachi-32
Pakistan
Prof. Dr. PHILIP WILLIAM LE QUESNE
Department of Chemistry
Northeastern University
360 Huntington Avenue
Boston, MA 02115
USA
ISBN-13:978-3-642-74019-0 e-ISBN-13:978-3-642-74017-6
DOl: 10.1007/978-3-642-74017-6
Library of Congress Cataloging-in-Publication Data. Natural products chemistry / Alta-ur
Rahman, Philip W. Le Quesne, eds. p. cm. Proceedings of the 3rd International Symposium
and Pakistan-U.S. Binational Workshop on Natural Products Chemistry, held in Karachi,
Pakistan, Jan. 1988. Includes bibliographies and index. 1. Natural products-Congresses.
I. Rahman, Alta-ur-, 1942- II. Le Quesne, Philip W. III. International Symposium and Paki
stan-U.S. Binational Workshop on Natural Products Chemistry (3rd. : 1988: Karachi, Pakistan)
QD415.A1N381988 547.7-dc 19 88-28145
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Preface
Natural product chemistry has undergone an explosive growth during the
latter half of the current century. This has been brought about by a
number of factors. One of these has been the growing number of sub
stances from natural sources which display interesting pharmacological
activities. These include antibiotics, anti-tumor agents, immunostimu
lants, drugs affecting the cardiovascular and central nervous systems,
analgesics etc. Another factor has been the improvements made in the
technology of isolation processes which includes the development of
such techniques as high pressure liquid chromatography which has al
lowed the rapid isolation of substances which were previously diffi
cult to obtain by classical procedures. The most important factor has
been the development of new spectrosopic techniques which have opened
up whole new vistas in this exciting field. Prominent in these advan
ces has been the advent of powerful superconducting magnets with very
stable magnetic fields, and pulse NMR in which the duration, direction
and phases of pulses can be accurately controlled by means of mini
computers. These have heralded the advent of two-dimensional NMR spec
troscopy which has now come to be routinely employed in unravelling
complex structures. No less important, though somewhat less dramatic,
have been the advances made in the field of mass spectroscopy where
new ionization techniques such as positive and negative fast atom bom
bardment, field desorption, chemical ionization etc. have allowed the
mass spectra of larger non-volatile substances to be recorded.
The field of organic synthesis has seen equally rapid advances. The
emphasis has been in the development of new stereoselective methods
for achieving specific synthetic transformations. The exciting synthe
tic approaches in the field of macrolide antibiotics, anti-tumor agents
and other biologically important natural products serve to exemplify
these developments.
The 3rd International Symposium and Pakistan - U.S. Binational Work
shop on Natural Products Chemistry, which was organised in Karachi in
January 1988 served to illustrate the frontiers of natural product che
mistry as they stand today. The distinguished scientists who partici
pated in the Symposium and presented Plenary lectures reflect the high
standards of chemistry that was presented during this conference, as
in the previous two conferences organised by us in Karachi in 1984
and 1986.
The present proceedings volume contains material which should be
of interest to a large number of synthetic organic chemists, phyto
chemists and biochemists. The first few chapters are concerned with
the use of modern spectroscopic techniques in natural products che
mistry. These are followed by articles on stereoselective synthesis,
biosynthesis and structure elucidation of natural products. In view
of space restrictions, we have had to shorten the presentations by
Pakistani scientists in this volume in order to include the articles
from foreign scientists.
It would be apparent from the galaxy of eminent scientists who con
tributed to this conference that all in all it was a most exciting
feast of chemistry which everyone thoroughly enjoyed. Of course all
of it would not have happened, were it not for the staff and students
VI
of H.E.J. Research Institute of chemistry who worked so tirelessly to
ensure its success - to them we owe our gratitude. But behind every
major conference there are the sponsoring agencies who provide the
financial support. In this case the two major sponsors were G.T.Z.
(West Germany) and N.S.F. (U.S.A.). Other international and national
agencies who contributed to the conference are UNESCO, ISESCO, IFS,
PSF, Brit~sh Council, International Seminar in Chemistry, Third World
Academy of Sciences and Hamdard Foundation Pakistan.
One of us (Prof. Atta-ur-Rahman) wishes to thank Miss Khurshid
Zaman for her assistance in the preparation of the index, and Mr.
Mahmood Alam for secretarial help.
This volume is dedicated to Prof. Salimuzzaman Siddiqui on his
91st birthday.
Summer 1988 ATTA-UR-RAliMAN
Sc.D. (Cantab.)
PHILIP W. LE QUESNE
Contents
Applications of NMR in Biochemistry and Biosynthesis
A.I. Scott (With 15 Figures) ................................... 5
NMR Techniques for the Structure Elucidation and Conformational
Analysis of Natural Products
G.A. Cordell, G. Blask6, M.O. Hamburger, Ze-Yuan Luo,
H. Shieh, D.C. Lankin, and H. Wagner (With 10 Figures) ......... - 19
NMR Solutions to Problems of Connectivity
in the Structural Elucidation of Natural Products
D.S. Rycroft (With 12 Figures) ..................•..•....•....•. 43
Newer Applications of Circular Dichroism in Natural
Products Chemistry
R.C. Cambie, P.C. Ho, K. Netzke, W. Schoenfelder,
F. Snatzke, G. Snatzke, and J. Schulte (With 17 Figures) 67
Novel Carbohydrate Transformations Discovered en route
to Natural Products
B. Fraser-Reid, R. Mootoo, V. Date, and S. Handa ......•........ 89
New Reagents and Methods for the Synthesis of fi-Lactams,
Peptides and Oligonucleotides
I. Ugi, J. Achatz, M. Baumgartner-Rupnik, B. Danzer, C. Fleck,
G. Glahsl, R. Herrmann, P. Jacob, C. Kambach, R. Karl, M. Klein,
B. Landgraf, P. Lemmen, H. Martin, G. Neyer, R. Obrecht, and
B. Westinger ............•......................•........•...... 107
General Strategies for the Asymmetric Synthesis of
Oxygenated Natural Products
S.F. Martin •.................................•.•............•.. 135
Total Synthesis of Nitrogen-Containing Natural Products
via Nitroso Diels-Alder Reaction
C. Kibayashi (With 13 Figures) ................•................ 155
Synthetic Studies in the Alkaloid Field
C. Szantay, G. Kalaus, L. Szabo, M. Incze, Z. Kardos-Balogh,
and F. S6ti (With 2 Figures) .........•....•.•.................. 175
Recent Progress in Our Indole Alkaloid Synthesis
I. Ninomiya ................................................•.•. 187
Synthetic Approaches to Carbazole Alkaloids
J. Bergman and B. Pelcman (With 2 Figures) ......•......•...... 215
Isoquinoline Alkaloid Synthesis via Arynes
L. Castedo and E. Guitian ..........•.........•..••.....•.•..... 235
2
Biosynthetic Studies of Protoberberine and Related Alkaloids
Using Plant Cell Cultures
M. Rueffer (With 3 Figures) 247
Secondary Metabolism in Cell Cultures of Some Terpenoid
Indole Alkaloid Producing Plants
R. Verpoorte, R. van der Heijden, J. Schripsema,
T. van der Leer, E.J.M. Pennings, P.A.A. Harkes,
S.S. Hoekstra, J.J. Meijer, and H.J.G. ten Hoopen
(With 6 Figures) •................•..............•.....•...•.... 257
Synthetic, Multi-Deuteriated Cholesterol as a Quantitative
Probe of the Formation of Cholesterol Oxidation Products
B.A. Wasilchuk, P. Feibush, P.W. Le Quesne, and P. Vouros
(With 9 Figures) .....................................•....•.... 275
Discovery and Chemistry of Naturally-Occurring Anti
cancer Agents
J.M. Cassady, Ching-Jer Chang, and R.G. Cooks (With
6 Figures) ....................................•...............• 291
Stereochemical Studies on Pre-anthraquinones and Dimeric
Anthraquinone Pigments
G. Billen, U. Karl, T. Scholl, K.D. Stroech, and W. Steglich
(With 1 Figure) ...••.......•...................•.•...•...•..... 305
Peptide Siderophores from Pseudomonas
H. Budzikiewicz (With 2 Figures) ...•.•..•.....•...•...•...•.... 317
Structure of Amavadin, the Vanadium Compound of
Amanita muscaria and Selective Binding of Vanadium
E. Bayer (With 6 Figures) ...................................... 335
Micro-chemical Research Pattern and the Prospects of Its
Industrial Development in the Developing Countries
S. Siddiqui .•.....•................................•••......... 345
Isolation and Structural Studies on New Natural Products
of Potential Biological Importance
Atta-ur-Rahman .......................................•.....•.•. 351
Isolation and Structural Studies on Chemical Constituents
from Some Plants and Marine Organisms of Pakistan
V.U. A,hmad, M.S. Ali, N. Bano, S. Bano, A. Fatima,
I. Fatima, K. Fizza, T.A. Farooqui, M.A. Khan,
S. Perveen, S. Qazi, T. Rasheed, G. Rizwani, V. Sultana,
K. Usmanghani, and Shafiuddin ......•....•..••....•...•..•..••.. 355
Subject Index .••..•.....•........••.••...••..•.....•.•••.••.... 359
Contributors
You will find the addresses at the beginning of the respective contribution
Achatz, J. 107 Landgraf, B. 107
Ahmad, V.U. 355 Lankin, D.C. 19
Ali, M.S. 355 Leer, van der 257
Bano, N. 355 Lemmen, P. 107
Bano, S. 355 Le Quesne, P.W. 275
Baumgartner-Rupnik, M. 107 Luo, Ze-Yuan 17
Bayer, E. 335 Martin, H. 107
Bergman, J. 215 Martin, S.F. 135
Billen, G. 305 Meijer, J.J. 257
Blasko, G. 19 Mootoo, R. 89
Budzikiewicz, H. 317 Netzke, K. 67
Cambie, R.C. 67 Neyer, G. 107
Cassady, J.M. 291 Ninomiya, I. 187
Castedo, L. 235 Obrecht, R. 187
Chang, Ching-Jer 291 Pelcman, B. 215
Cooks, R.G. 291 Pennings, E.J.M. 257
Cordell, G.A. 19 Perveen, S. 355
Danzer, B. 107 Qazi, S. 355
Date, V. 89 Rahman, Atta-ur- 351
Farooqui, T.A. 355 Rasheed, T. 355
Fatima, A. 355 Rizwani, G. 355
Fatima, I. 355 Rueffer, M. 247
Feibush, P. 275 Rycroft, D.S. 43
Fizza, K. 355 Schoenfelder, W. 67
Fleck, C. 107 Scholl, T. 305
Fraser-Reid, B. 89 Schripsema, J. 257
Glahsl, G. 107 Schulte J. 67
Guitian, E. 235 Scott, A.1. 5
Hamburger, M.O. 19 Shafiuddin 355
Handa, S. 89 Shieh, H. 19
Harkes, P.A.A. 257 Siddiqui, S. 345
Heijden, R. van der 257 Snatzke, F. 67
Herrmann, R. 107 Snatzke, G. 67
Ho, P.C. 67 Soti, F. 175
Hoekstra, S.S. 257 Steglich, W. 305
Hoopen, ten H.J.G. 257 Stroech, K.D. 305
Incze, M. 175 Sultana, V. 355
Jacob, P. 107 Szabo, L. 175
Kalaus, G. 175 Szantay, C. 175
Kambach, C. 107 Ugi, 1. 107
Kardos-Balogh, z. 175 Usmanghani, K. 355
Karl, R. 107 Verpoorte, R. 257
Karl, u. 305 Vouros, P. 275
Khan, M.A. 355 Wagner, H. 19
Kibayashi, C. 155 Wasilchuk, B.A. 275
Klein, M. 107 Westinger, B. 107
Applications ofNMR in Biochemistry and Biosynthesis
A. I. SCOTT
Texas A & M University, Chenistry Department,
College Station, TX 77843, USA
I. lH-NMR Spectroscopy of Catalysis
A splendid illustration of the use of 500 MHz 1H NMR is provided by the water suppressed
time course of porphyrin biosynthesis where porphobilinogen (pBG), the substrate for uro'gens I and
III and Vitamin B 12 is transformed into the apparent product uro'gen I which turns out to be a
chemical artifact. Thus, during incubation ofPBG with the enzyme, PBG dearninase ([D]; Fig. 1; Mr
33,0(0) the product released from the enzyme is pre-uro'gen, or hydroxymethyl bilane CHMB),
whose characteristic spectrum (Fig. 1) (t1/2 = 180 sec/30°C) can be seen transiently when the reaction
is carried out at 40C [12a,b]. The NMR method also uniquely defines HMB as the substrate for the
second enzyme, uro'gen III cosynthetase. In the absence of the latter enzyme, the cyclization of the
head-to-tail tetrapyrrole HMB takes place spontaneously. The deep-seated intra-molecular
rearrangement of HMB to uro'gen III can now be studied by this technique.
p p
P A P
A P
)j
..
..
Nita A p A
A P A P
PSG Hydroxymelhylbilane Uro'gen I
33,
,.,
'·2 4·0 3-0 20 pplft
Figure 1: Fonnation of uro'gen 1 and HMB from PBG.
6
Perhaps this is indeed a unique case, for in our second example, Nature is not helpful in
releasing the intennediate from the cyclizing enzyme for NMR viewing. Thus the enzyme iso-Pen
synthetase, which converts the tripeptide ACV to isopenicillin N (Fig. 2) [3] forms both ~-Lactam and
thiazolidine rings synchronously on the NMR time scale without release from the enzyme. These
examples bring us logically to the ultimate search for structural information during the catalytic cycle,
by temporal resolution of the spectra of covalently bound intermediates.
+
ACY
H'N~~~S)(H'
H'I 0 J-~7\ CH,
CO,H 0 H 'cO,H
Isopenic,lIin N 5
o
min.
3Omin.
120min.
••
1-'
ppm
Figure 2: NMR Time Course of Penicillin Biosynthesis.
II. Studyin~ EnzYme Mechanism by.Uc NMR.
Almost all enzymatic processes utilize multistep reactions during catalysis, and the
characterization of each of these stages is essential if one is to understand enzyme mechanism at the
molecular level. Earlier investigators have used spectrophometric methods for characterizing
enzyme-catalyzed reactions, whereas inhibitors that form stable "transition state analogues" have been
examined by other techniques that require long periods of data accumulation, for example, X-ray
analysis. However, the advent of NMR and its subsequent use in enzymology are beginning to
provide a novel and penetrating probe for elucidating enzyme mechanism by directly characterizing
intermediates fonned in catalysis. The studies of "transition state analogues" allow access to the
unique properties of enzymes that enable them to stabilize labile intermediates and therefore achieve
their remarkable catalytic efficiency. We discuss fIrst the structures of an enzyme-inhibitor adduct of
the serine protease trypsin and compare the results of direct observation by 13C NMR with the
structural infonnation inferred by more classical techniques. We then review the powerful