Table Of ContentFORTSCHRITTE
DER CHEMIE ORGANISCHER
NATURSTOFFE
PROGRESS IN THE CHEMISTRY
OF ORGANIC NATURAL PRODUCTS
PROGRES DANS LA CHIMIE
DES SUBSTANCES ORGANIQUES
NATURELLES
HERAUSGEGEBEN VON EDITED BY REDIGE PAR
L. ZECHMEISTER
CALIFORNIA INSTITUTE OF TECHNOLOGY, PASADENA
EINUNDZWA .NZIGSTER BA.ND
TWENT1::=FIRST VOLUME VINGT",ET6UNIEME VOLUME
VERFASSER AUTHORS AUTEURS
R. BANGERT . J. BONNER . H. BROCKMANN . L. CROMBIE
L. JAENICKE . C. KUTZBACH . A. D. MEBANE . H. MUXFELDT
W.OROSHNIK
MIT 14 ABBILDUNGEN WITH 14 FIGURES AVEC 14 ILLUSTRATIONS
WI EN· S P R I N G E R. V E R LAG· 1963
ALLE RECHTE, INSBESONDERE DAS DER OBERSETZUNG
IN FREMDE SPRACHEN, VORBEHALTEN
OHNE AUSDROCKLICHE GENEHMIGUNG DES VERLAGES
1ST ES AUCH NICHT GESTATTET, DIESES BUCH ODER TEILE DARAUS
AUF PHOTOMECHANISCHEM WEGE (PHOTOKOPlE, MIKROKOPlE)
ODER SONSTWlE ZU VERVlELFALTIGEN
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NO PART OF THIS BOOK MAY BE REPRODUCED IN ANY FORM,
BY PHOTOSTAT, MICROFILM, OR ANY OTHER MEANS, WITHOUT WRITTEN
PERMISSION FROM THE PUBLISHERS
© 1963 BY SPRINGER-VERLAG/WIEN
Softcover reprint of the hardcover 15t edition 1963
LIBRARY OF CONGRESS CATALOG CARD NUMBER AC 39-1015
ISBN-13: 978-3-7091-7150-9 e-ISBN-13: 978-3-7091-7149-3
001: 10.1007/978-3-7091-7149-3
Inhaltsverzeichnis.
Contents. - Table des matieres.
The Biosynthesis of Rubber. By JAMES BONNER, California Institute of
Technologie, Pasadena, California .................................. .
I. Distribution of Rubber ............................................ .
II. Latex............................................................. 2
Structure and Configuration............. . . . . . . . . . . . . . . . . . . . . . . . . . '2
III. Biogenesis of the Monomer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 4
IV. Polymerization..................................................... 10
V. Further Problems. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. I I
References ........................................................... 13
The Polyene Antifungal Antibiotics. By W. OROSHNIK, Central Research
Laboratory Shulton, Clifton, New Jersey, and A. D. MEBANE, Ortho
Research Foundation, Raritan, New Jersey......................... 17
I. Introduction...................................................... 18
II. Ultraviolet Spectra. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
I. General Observations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
2. The Tetraenes....... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 23
3. The Pentaenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 24
4. The Methylpentaenes .......................................... 24
5. The Hexaenes ................................................ , 24
6. The Heptaenes................................................ 24
III. Structural Elucidation... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 26
I. General Features. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 26
2. Mycosamine................................................... 28
3. Retro-Aldol Cleavage ......... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 30
4. Fungichromin (Lagosin) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 32
5· Filipin........................................................ 37
6. Other Methylpentaenes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 39
7. Pimaricin..................................................... 40
8. Nystatin and Other Tetraenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 43
9. Pentaenes and Hexaenes....................................... 45
10. Trichomycin and Other Heptaenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 46
IV. Biogenetic Relationships........................................... 51
V. Tables........................................................... 56
I. Typical Tetraenes: Spectral Data. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 56
2. Typical Pentaenes: Spectral Data. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 5()
3. Typical Methylpentaenes: Spectral Data. . . . . . . . . . . . . . . . . . . . . . . .. 57
4. Typical Hexaenes: Spectral Data........................ . . . . . . .. 57
5. Typical Heptaenes: Spectral Data.............. . . . . . . . . . . . . . . . .. 57
IV Inhaltsverzeichnis. - Contents. - Table des matieres.
6. Tetraenes: Physical and Chemical Properties. .. . . .. . . . . .. .•. . . . .. 58
7. Pentaenes: Physical and Chemical Properties.. . . . .. . .. . .. . . . .. .. 62
8. Methylpentaenes: Physical and Chemical Properties.. . . . . . . . . . . . .. 64
9. Hexaenes: Physical and Chemical Properties. . . . . . . . . . . . . . . . . . . .. 66
10. Heptaenes: Physical and Chemical Properties.................... 66
References ..............., . ... . .. . . . . . . . . . . . . . . . . . .. . . . .. . . . .. . . . . ... 72
Die Chernie der Tetracycline. Von H. MUXFELDT und R. BANGERT,
Department of Chemistry, The University of Wisconsin, Madison,
Wisconsin. . . . . . . . . . • . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
I. Einleitung........................................................ 80
II. KonstitutionsaufkHirung ........................................... 82
1. Terramycin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 82
Alkalischer Abbau . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . • . . . .. 83
Saurer Abbau. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 87
Reduktiver Abbau. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 90
2. Aureomycin.................................................... 91
3. 6-Desmethyl-tetracycline ........................................ 96
4. 5 a,II a-Dehydro-7-chlor-tetracyclin ........................., ...... 96
5. 2-Acetyl-2-descarboxamido-tetracycline............................ 97
III. Weitere chemische Eigenschaften . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 98
1. Reaktionen am C(2).. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
2. Reaktionen am C(4). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 100
3. Reaktionen am C(6). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 102
4. Reaktionen am C(l1a) und C(12a) ................................. 108
IV. Biogenese der Tetracycline.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 113
V. Versuche zur Synthese von Tetracyclinen . . . . . . . . . . . . . . . . . . . . . . . . . .. !I5
Literaturverzeichnis ............................................... 116
Anthracyclinone und Anthracycline (Rhodornycinone, Pyrrornycinone
und ihre Glykoside). Von HANS BROCKMANN, Organisch-chemisches
Institut der Universitat Gottingen ................................. 121
I. Einleitung........................................................ 122
II. Isolierung der Anthracyclinone und Anthracycline .................... 123
I. Gewinnung der s-Pyrromycinon-glykoside und Pyrromycinone ...... 124
Cinerubin A und B ............................................. 124
Pyrromycin und Pyrromycinone ................................. 124
2. Gewinnung der Rhodomycinone, Iso-rhodomycinone und ihrer
Glykoside. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 125
Trennung von RhodomycinonjIso-rhodomycinon-Gemischen ......... 126
Trennung von Rhodomycinen und Iso-rhodomycinen ............... 127
III. Die Anthracyclinone. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . .. 127
I. Vorbemerkungen zur Struktur der Anthracyclinone . . . . . . . . . . . . . . .. 127
2. Zur Konstitutionsermittlung der Anthracyclinone. . . . . . . . . . . . . . . . .. 130
Die Aufklarung des Chromophors ................................ 131
Die Anellierung des alicyclischen Ringes.......................... 133
v
Inhaltsverzeichnis. - Contents. - Table des matieres.
Die Substituenten an Ring A .................................... 134
Schreibweise und Bezifferung der Anthracyclinon-Formeln. . . . . . . . .. 137
3. Konstitution der Anthracyclinone ................................ 137
A. Iso-rhodomycinone ........................................... 137
e-Iso-rhodomycinon. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 137
C-Iso-rhodomycinon ............................ '" ........... 139
,B-Iso-rhodomycinon. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 140
B. Rhodomycinone ............................................. 140
e-Rhodomycinon ............................................ 140
C-Rhodomycinon ............................................ 141
,B-Rhodomycinon ............................................ 141
y-Rhodomycinon ............................................ 145
6-Rhodomycinon ............................................ 145
C. Pyrromycinone .............................................. 146
1)-Pyrromycinon ............................................. 146
e-Pyrromycinon ............................................. 151
C-Pyrromycinon ............................................. 151
D. Aklavinone ................................................. 154
Aklavinon .................................................. 154
7-Desoxy-aklavinon . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 154
4. Die KMR-Spektren der Anthracyclinone .......................... 155
5. Zur Stereochemie der Anthracyclinone ............................ 160
6. Zur Biogenese der Anthracyclinone.. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 163
IV. Die Anthracycline ................................................. 170
I. Die Zucker der Anthracycline ................................... 171
Rhodosamin ................................................... 171
2-Desoxy-L-fucose ........... " ............. '" ... '" ........... 173
Rhodinose ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 173
2. Anthracycline des e-Pyrromycinons .......... : .................... 174
Pyrromycin .................................................... 174
Cinerubine . . . . . . . . . . . •. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 175
Rutilantine .................................................... 176
3· Anthracycline der Rhodomycinone ... . . . . . . . . . . . . . . . . . . . . . . . . . . .. 176
Rhodomycin A . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 176
Rhodomycin B ................................................. 177
y-Rhodomycine ................................................. 177
Iso-rhodomycin A. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 178
Antibiotica der Mycetin-ViolaIin-Gruppe .......................... 179
4· Anthracycline des Aklavinons .................................... 179
Aklavin ....................................................... 179
Literaturverzeichnis ............................................... 179
Folsiure und Folat-Enzyme. Von L. JAENICKE und C. KUTZBACH,
Physiologisch-chemisches Instiut der Universitat KOln............... 183
I. Einleitung . . . . . . . . . . . . . . . . • . . • . . . . . . . . . . . . . . . . . . . . . • • . . . . . . . . . . .. 184
II. Das Vitamin Folsaure ....•..•..........•...•....••............... 187
I. Entdeckung der Foisaure und ihrer Konjugate ....•.............• 187
VI Inhaltsverzeichnis. - Contents. - Table des matieres.
2. Konjugat-spaltende Enzyme .................................... 190
3. Vorkommen. Bedarf und Ausscheidung .......................... 190
III. Auf- und Abbau der Folsaure-Cofaktoren ........................... 192
1. Biogenese der Folsaure ......................................... 192
2. Biologischer Abbau der Folsaure ................................ 195
3. Enzymatische Reduktion der Folsaure zum Cofaktor .............. 197
IV. Chemie der Folat-Verbindungen .................................... 199
1. Folsaure ...................................................... 199
a. Isolierung .................................................. 199
b. Konstitution und physikalische Eigenschaften. . . . . . . . . . . . . . . . .. 200
c. Chemische Eigenschaften ..................................... 201
d. Folsaure-Synthesen .......................................... 203
2. Reduktion von Folsaure.......... . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 204
a. Dihydrofolsaure und das Problem der Dihydrofolat-Isomerie .... 204
b. 5,6,7,8-Tetrahydro-folsaure ................................... 207
3. Mit Einkohlenstoff-Korpern substituierte Folsauren ................ 209
a. 10-Formyl-folsaure........................................... 209
b. 10-Formyl-tetrahydrofolsaure ................................. 209
c. 5-Formyl-tetrahydrofolsaure .................................. 21 I
d. 5,10-Methinyl-tetrahydrofolsaure .............................. 212
e. 5-Formimino-tetrahydrofolsaure ............................... 215
f. 5,ro-Methylen-tetrahydrofolsaure .... " ........................ 216
g. 5-Methyl-tetrahydrofolsaure ................................... 219
4. Folsaure-Analoge............................................... 220
5. Spektren von Folat-Verbindungen ............................... 222
6. Analyse und Trennung von Folsaure-Verbindungen ................ 225
a. Chemische Verfahren ........................................ 225
b. Polarographie ............................................... 225
c. Mikrobiologische Methoden . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 226
d. Chromatographische Trennung ................................ 227
V. Das Einkohlenstoff-Reservoir ...................................... 229
1. Herkunft der Ameisensaure ..................................... 229
2. Glycin als Quelle von Einkohlenstoffkorpern ...................... 231
3. Der Einkohlenstoff-Donator Serin ............................... 232
4. Herkunft der Methylgruppe .................................... , 233
VI. Folat-katalysierte Enzym-Reaktionen ............................... 236
1. Der Transhydroxymethylierungs-Cyclus ........................... 236
a. Serin-Aldolase............................................... 236
b. Transhydroxymethylierungs-Reaktionen ........................ 239
c. Methylentetrahydrofolat-Dehydrogenase ........................ 239
2. Methylengruppen-Genese........................................ 240
a. Thymidylat-Bildung . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 240
b. Methylentetrahydrofolat-Reduktase: 5-Methyl-tetrahydrofolsaure.. 242
c. Methionin-Bildung ........................................... 243
~. Die Gesamt-Reaktion ..................................... 243
fl. Zusammenhange zwischen Foisaure und Vitamin B1Z' ••••••• , 244
y. Der Acceptor der Methylgruppe ..•......................... 245
Inhaltsverzeichnis. - Contents. - Table des matieres. VII
3. Transformylierungs-Cyclen .......... . . . . . . . . . . . . . . . . . . . . . . . . . . .. 246
a. Abbau von Histidin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 246
b. Deacylase und Glutamyl-Transferase .......................... 247
c. Aktivierte Ameisensaure im Purin-Stoffwechsel.... . . . . . . . . . . . .. 248
iX. Vergarung von Purinen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 248
fl· Tetrahydrofolat-Formylase ................................. 249
y. Transformylierungen ...................................... 251
VII. Zusammenfassung ................................................ 253
Literaturverzeichnis ............................................... 254
Chemistry of the Natural Rotenoids. By L. CROMBIE, Department of
Chemistry, University of London King's College, London ........... 275
I. Introduction .................................................... 275
II. General Remarks on Rotenone and the Rotenoids .................. 276
1. Isolation ................................................... " 278
2. Colour Tests .................................................. 278
3· Nomenclature ................................................. 279
III. Stereochemistry of Rotenone ..................................... 279
IV. Chemistry of Rotenone ........................................... 284
V. The Rotenolones and Isorotenolones............................... 290
1. The A and B Series ......................................... " 290
2. The C and D Series. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 294
VI. The Rotenoids ................................................ " 295
1. Stereochemistry.............................................. 295
2. Deguelin .................................................... 296
3· Elliptone.................................................... 297
4· Munduserone ................................................ 298
5· iX-Toxicarol ................................................ " 299
6. Sumatrol ................................................. _ .. 301
7· Malaccol .................................................... 302
8. Pachyrrhizone ............................................... 303
9· Erosone..................................................... 304
10. Dolineone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 304
VII. Biogenesis and Biogenetic Connections of the Rotenoids ............ 305
VIII. Synthesis in the Rotenoid Group................................. 309
Addendum ........................................................... 316
References .......................................................... 316
Namenverzeichnis. Index of Names. Index des Auteurs ... . . . . . . . . . . . . . . • . .. 326
Sachverzeichnis. Index of Subjects. Index des Matieres . . . . . . . . . . . . . . . . . . . .. 340
The Biosynthesis of Rubber.
J
By AMES BONNER, Pasadena, California.
With 2 Figures.
Contents.
Page
1. Distribution of Rubber ............................................ .
II. Latex............................................................. z
Structure and Configuration...................................... z
III. Biogenesis of the Monomer ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 4
IV. Polymerization..................................................... TO
V. Further Problems... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. IT
References ........................................................... 13
Of the major biosynthetic pathways of the plant, that associated
with the synthesis of rubber has been among the last to be elucidated.
All that we know today concerning isoprenoid biogenesis is information
acquired since 1949, much of it since 1956. Today, however, rubber
biosynthesis may be considered as a problem solved. We can plot out
in intimate detail the complete pathway by which carbon atoms present
in common plant metabolites such as carbohydrates are converted to
the polyisoprene molecule.
I. Distribution of Rubber.
All species of higher plants possess, it is believed, the capability of
synthesizing varied species of isoprenoids. Amongst the widely distributed
isoprenoids are the carotenoids, the steroids, the long-chain isoprenoid
alcohols, such as phytol, and the isoprenoid tails of the ubiquinones.
Ubiquitous distribution is not, however, a property of rubber. Rubber
is synthesized by but some 2000 of the 400000 species of higher plants.
The distribution of the ability to synthesize rubber appears to be random
through the higher plant family tree, with the exception that such ability
does not occur in any monocotyledonous plant such as, for example,
the grasses, nor in any of the gymnosperms, as, for example, the pines
and their allies (I3). Of the 2000 species which produce rubber, only a few
produce it in large quantity. Amongst the principal rubber accumulating
plants are, Ficus elastica RoxB. (the rubber plant), Parthenium argentatum
Fortschritte d. Chern. org. Naturst. XXI.
2 J. BONNER:
----=~c=-c=_========
GRAY (the guayule), and Taraxicum kok saghyz RODIN (the Russian
dandelion). The rubber tree of commerce, Hevea braziliensis MUELL.
supplies, however, all but an infinitesimal amount of the world's cultivated
natural rubber. A small number of tropical species, including Palaquium
gutta BURCK and Mimusops balata GAERTN., produce an isomer of rubber,
gutta.
II. Latex.
In the rubber producing species, rubber is contained in general in
specialized cells, the latex vessels. Latex is the protoplasm of these
cells and contains therefore, in addition to rubber particles stabilized
by protein, all of the usual intracellular components, enzyme molecules,
mitochondria, nuclei, and in all probability, ribosomes, as well as low
molecular weight metabolites. The enzymes of latex include those which
participate in the biosynthesis of rubber as will be discussed below.
The concentration of rubber in latex may be very high indeed, 30% in
the case of H evea braziliensis.
The latex vessels of Hevea and of the other principal rubber-producing
species are located in the bark, and are interconnected to form a vast
continuous network (Figs. I, 2). Latex within this network is under
positive hydrostatic pressure (II).
If a cut into the lactiferous system is made, latex pours out through
the opened vessels, the flow continuing for minutes or hours depending
upon the species involved. This flow ultimately ceases, probably often
due to coagulation of the latex by the action of microorganisms. The
vessel again takes up water to restore its hydrostatic pressure to normal,
and in Hevea in particular, rubber is again synthesized. It is this feature
of Hevea, the feature of rapid regeneration of the rubber content of
the latex vessels, which makes it the rubber plant of choice. A rubber
tree may be tapped on alternate days throughout the bulk of its life,
and yield a constant or increasing amount of rubber, over the course
of 30 years or more.
Structure and Configuration.
Rubber and gutta are both polyisoprenoids, in which isoprene residues
are linked together through lA-linkages. The polymer molecule is of
the order of 500 to 5000 residues long, in the case of rubber; of the order
of 100 residues long in the case of gutta (Guttapercha, Balata). In rubber
(VI, p. 8) the double bonds of each isoprene residue possess cis configuration,
and rubber is therefore an all-cis-polyterpene. In gutta, on the other
hand, all isoprene double bonds possess trans configuration. Hybrid
molecules containing both cis and trans double bonds do not appear
to occur, either in gutta or in rubber (20).
References, pp. I3-I6.
Biosynthesis of Rubber. 3
Fig. I. High yielding tree of HCD'ea brasiliensis under tapping and with latex dripping from tapping cut.
The sloping tapping cut intersects the latex vessels at approximately right angles. At each tap a fresh ca.
I rnm. of bark is removrd, so the tapping cut moves downward. [Conrtpsy, Rubher Research Institute
of :\Ialaya, Kuala Lumpur.l
1*
