Table Of ContentFORTSCHRITTE
DER CHEMIE ORGANISCHER
NATURSTOFFE
PROGRESS IN THE CHEMISTRY
OF ORGANIC NATURAL PRODUCTS
BEGRUNDET VON' FOUNDED BY
L. ZECHMEISTER
HERAUSGEGEBEN VON· EDITED BY
W. HERZ H. GRISEBACH G. W. KIRBY
TALLAHASSEE, FLA. FREIBURG i. BR. GLASGOW
VOL. 36
VERFASSER . AUTHORS
C. W. J. CHANG· I. FLAMENT· J. A. MATSON· T. NISHIDA
G. OHLOFF . F. W. WEHRLI· A. J. WEINHEIMER
1979
SPRINGER-VERLAG WIEN GMBH
Mit 11 Abbildungen. With 11 Figures
This work is subject to copyright
All rights are reserved, whether the whole or part of the material is concerned, specifically those
of translation, reprinting, fe-use of illustrations, broadcasting, reproduction by photocopying
machine or similar means, and storage in data banks
© 1979by Springer-VerlagWien
Originally published by Springer-Verlag Wien-New York in 1979
Softcover reprint of the hardcover 1st edition 1979
Library of Congress Catalog Card Number AC 39-1015
ISSN 0071-7886
ISBN 978-3-7091-3267-8 ISBN 978-3-7091-3265-4 (eBook)
DOI 10.1007/978-3-7091-3265-4
Inhaltsverzeichnis. Contents
Mitarbeiterverzeichnis. List of Contributors ..... . .................. VII
The Use of Carbon-13 Nuclear Magnetic Resonance Spectroscopy in Natural Products
Chemistry. By F. W. WEHRLI and T. NISHIDA ................ .
1. Introduction ... 2
2. "c NMR Spectral Assignments. 2
2.1. Single Frequency Decoupling 3
2.2. Proton-Coupled Spectra .. 6
2.3. Isotopic Substitution. 12
2.4. Lanthanide Shift Reagents. 14
2.5. Spin-Lattice Relaxation 16
3. "c Spectral Data of Natural Products. 23
3.1. Terpenoids and Steroids. 24
Monoterpenes . 24
Sesquiterpenes 33
Diterpenes . . . ........ . 55
Terpenoids C" (20 < n < 30) 81
Steroids .. 104
Carotenoids and Related Terpenoids .. 122
3.2. Alkaloids ... 128
3.3. Purines, Pteridines, Flavonoids, and Related Substances 163
3.4. Carbohydrates ......... . 174
3.5. Antibiotics .. 181
4. Biosynthetic Studies 183
5. Concluding Remarks .. 194
References 195
Addendum ... 216
VI Inhaltsverzeichnis. Contents
The Role of Heteroatomic Substances in the Aroma Compounds of F oodstoffs. By
O. OHWFF and l. FLAMENT ...................................... 231
I. Introduction 231
II. Pyranones. Furanones, and Related Aroma Compounds 238
Ill. Sulfur Compounds 243
IV. Thiophenes 252
V. Thiazoles .. 255
VI . Oxazoles and Oxazolines 258
VII. Pyrroles .' 260
VIII. Pyn.l7incs 262
References 267
NaturaUy Occurring Cembranes, By A. J. WEINHEIMER, C. W. J. CHANG, and J. A.
MATSON ....................................................... 285
l. Introduction ........................................................... 286
A. Nomenclature ......................... , ............................. 287
B. Structural Representation ............................................. 288
C. Configurations ...................................................... 289
D. "Cembrane" ................................ . 290
E. Distribution of Cembranes 291
II. Natural Sources ..... 291
A. Plants.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .................. 291
1. Resinous Plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 291
2. Tobacco........................................................ 305
3. Miscellaneous Plants .............................................. 315
B. Insects ................. . 319
C. Marine Invertebrates. 320
III. Synthesis ..... . 349
A. (±)-Cembrane
349
B. (±)-Cembrene
350
C. Other Cembranoids ........................ .
352
IV. Biosynthesis of Cembranoids . 355
Tables 356
Addendum 370
References 381
Namenverzeichnis. Author Index 389
Sacbverzeicbnis. Subject Index 409
Mitarbeiterverzeichnis. List of Contributors
Chang, Assoc. Prof. Dr. C. W. J., Faculty of Chemistry, University of West Florida,
Pensacola, FL 32504, U. S. A.
Flament, Dr. I., Laboratoire de Recherches. Firmenich SA. Case Postale 239, CH-1211
Geneve 8, Switzerland.
Matson, Dr. J. A .. Research Associate, Department of Medicinal Chemistry and Pharma-
cognosy, University of Houston. Houston, TX 77004, U.S.A.
Nishida, Dr. T .. Swedish Tobacco Company. Research Department. P. O. B. 17007,
S-10462 Stockholm 17, Sweden.
Ohloff, Dr. G., Laboratoire de Recherches, Firmenich SA, Case Postale 239, CH-1211
Geneve 8, Switzerland.
Wehrli. Dr. F. W., Varian AG. Steinhauserstrasse. CH-6300 Zug, Switzerland.
Weinheimer, Prof. Dr. A. J .• Department of Medicinal Chemistry and Pharmacognosy,
University of Houston. Houston, TX 77004, U. S. A.
The Use of Carbon-13 Nuclear Magnetic
Resonance Spectroscopy in Natural Products
Chemistry
By F. W. WEHRLI, Varian AG, NMR Applications Laboratory,
Zug, Switzerland, and T. NISHIDA, Swedish Tobacco Company, Research
Department, Stockholm, Sweden
With 10 Figures
Contents
I. Introduction ............. . 2
2. l3C NMR Spectral Assignments. 2
2.1. Single Frequency Decoupling
2.2. Proton-Coupled Spectra. 6
2.3. Isotopic Substitution 12
2.4. Lanthanide Shift Reagents. 14
2.5. Spin-Lattice Relaxation 16
3. "c Spectral Data of Natural Products. 23
3.1. Terpenoids and Steroids ... 24
Monoterpenes .. 24
Sesquiterpenes 33
Diterpenes . 55
Terpenoids Cn (20 < n < 30) 81
Steroids ........... . 104
Carotenoids and Related Terpenoids . . ........... . 122
3.2. Alkaloids. . . ................. . 128
3.3. Purines, Pteridines, Flavonoids, and Related Substances 163
3.4. Carbohydrates ............................. . 174
3.5. Antibiotics. 181
4. Biosynthetic Studies 183
5. Concluding Remarks .. 194
References. 195
Addendum .................. . 216
Fortschritte d. Chern. org. Naturst. 36
F. W. WEHRLI and T. NISHIDA:
1. Introduction
Since the late 1950's when proton n. m. r. spectroscopy was first used
in organic natural products studies the technique has increasingly con-
tributed to the rapid advancement of this important area of chemistry.
Although the potential utility of 13C n. m. r. was recognized very early,
essentially no application of 13C n. m. r. appeared in the literature prior
to 1966 and 95% of the existing data are less than five years old.
The initially slow growth had its cause in inadequate instrumentation,
insufficient sensitivity being the main obstacle. This situation drastically
changed with the advent and commercial availability of broadband ex-
citation and Fourier transform methods, giving natural-abundance 13C
n. m. r. and its numerous chemical applications a tremendous impetus.
Today BC spectra can be recorded on sample quantities down to the
submilligram level, which until recently even withstood proton n. m. r.
Paralleling the development of experimental techniques considerable
progress has also been made on an understanding of spectral parameters,
in particular their stereochemical implications on natural products.
Although the large majority of data present up to now deals with known
structures, an adequate basis now exists which allows the chemist to use
the technique for tackling real problems on unknown molecules.
A few years ago HIGHET and SOKOLOSKI (1) in this series reviewed
newer n. m. r. methods in structure investigation of natural products by
devoting half of their review to describe the principle of pulsed Fourier
transform n. m. r. spectroscopy, general features and basic experimental
techniques related to BC n. m. r. spectroscopy. Several introductory re-
view articles have also appeared recently to demonstrate the usefulness
of l3C n. m. r. for structure analysis of natural products (2, 3) and in bio-
synthetic studies (4-9).
In order to avoid unnecessary duplication and since comprehensive
coverage would present an almost impossible task, the authors of the
present review have chosen to cover mainly the 1974-1977 literature and
to quote earlier primary literature only in exceptional cases. For topics
of more general nature the reader will be referred to the pertinent
specialist reports.
2. 13C NMR Spectral Assignments
Carbon-l 3 chemical shifts are readily obtained from the proton noise-
decoupled (PND) spectrum in which non-equivalent carbons resonate as
separate single lines. Although proton-coupled 13C spectra contain much
more information, they cannot, in general, be analyzed completely be-
R~ferences, pp. 195-229
The Use ofCarbon-13 Nuclear Magnetic Resonance Spectroscopy
cause of severe overlap of spin multiplets as they occur in the spectra of
complex organic molecules such as natural products. Moreover, recording
of such spectra demands up to two orders of magnitude more spectrometer
time. Fortunately, some of the inherent coupling information can also
be gained from the residual splitting patterns observed in the single-
frequency off-resonance decoupled (SFORD) spectra. A prerequisite for
any application of 13C n. m. r. spectroscopy is the proper and unambiguous
assignment of the resonances in the molecule under investigation. This
requirement is a stringent one and uncertainities which exist in the assign-
ment must be emphasized and clearly mentioned to avoid incorrect
assignments in future studies. In this section several recently developed
assignment techniques are reviewed. For a more detailed discussion of
this subject the reader is referred to Chapter 3 in Reference (10).
2. L Single Frequency Decoupling
When the proton decoupler frequency is at exact resonance of some
protons, the carbon atom directly bonded to them will appear as a
singlet (selective proton decoupling). Off-resonance irradiation, on the
other hand, causes compressed multiplets, characterized by a residual
splitting J , while from the multiplicity the number of attached protons
can be derived. The residual coupling r can be correlated with the
decoupler offset frequency D. F (in Hz) and the decoupler power y H2/2 rr
(in Hz)
(1)
This approximation is valid ify H2/2 rr» D. F and 1 JeH .
Incremental variation of the proton decoupler frequency provides a
set of spectra containing differently spaced residual multi plets. The effec-
tive l3C resonance frequencies are then linearly related to the decoupler
frequency. In this manner a series of straight lines is obtained which
intersect at the frequency which corresponds to the proton resonance
frequency. These experiments therefore afford a correlation between 13C
and lH chemical shifts (11).
However, off-resonance patterns of CH2's and CH's in complex or-
ganic molecules are not always clearly resolved multiplets. Instead rather
complicated multiline patterns are often obtained.
Recently deviations from simple first-order multiplets were syste-
matically studied and the utilization of off-resonance pattern recognition
applied to signal assignment and structure elucidation (12).
Basically two situations have been encountered, both of which lead
to deviations from simple first-order off-resonance patterns. The first case
j*
