Fortschritte der Chemie organischer Naturstoffe / Progress in

the Chemistry of Organic Natural Products 85, 1st Edition

Visit the link below to download the full version of this book:

https://medipdf.com/product/fortschritte-der-chemie-organischer-naturstoffe-prog
ress-in-the-chemistry-of-organic-natural-products-85-1st-edition/

Click Download Now

VI Contents

3.3. Surface-Associated Glycoproteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88

3.4. Extracellular Glycoproteins ................................ 92
3.5. "Cellular" Glycoproteins ................................. 97
3.6. Synthetic Glycopeptides and Glycoproteins . . . . . . . . . . . . . . . . . . . .. 101
4. Conclusions .............................................. 104
Acknowledgements ........................................... 105
References ................................................. 105

Carbazole Alkaloids IV
D. P. Chakraborty and S. Roy

I. Introduction ............................................. 128

A. Nomenclature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 129
B. Occurrence. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 129
II. Methods of Structure Elucidation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 132
A. Physical Methods ....................................... 132
1. Ultraviolet Absorption Spectra . . . . . . . . . . . . . . . . . . . . . . . . . . .. 133
2. IR Spectra .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 133
3. NMR Spectra. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 133
4. Mass Spectra ........................................ 143
5. X-ray Crystallography. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 144
B. Chemical Methods ...................................... 145
C. Synthesis .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 145
1. Synthesis from Monocyclic Systems . . . . . . . . . . . . . . . . . . . . . . .. 145
2. Synthesis from Bicyclic Systems .......................... 154
3. Synthesis from Tricyclic Systems. . . . . . . . . . . . . . . . . . . . . . . . .. 163
4. Synthesis of Carbazoles by Electrocyclisation ................. 165
5. Synthesis by Photolytic Methods .......................... 166
III. Biogenesis of Carbazole Alkaloids. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 168
IV. Biological and Therapeutic Properties of Carbazoles
and Carbazole Alkaloids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 170
V. Chemistry of Carbazole Alkaloids .............................. 175
A. Alkaloids from Higher Plants ............................. " 175
i) C l3 -Alkaloids ......................................... 175
1. 9-Carboethoxy-3-methylcarbazole . . . . . . . . . . . . . . . . . . . . . . . .. 175
2. Clausenol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 175
3. Clausenine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 176
4. 9-Formyl-3-methylcarbazole . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 176
5. Murrayaline B ...................................... 176
6. 2-Methyl-7-hydroxycarbazole or 2-Hydroxy-7-methylcarbazole .... 177
7. N-Methoxy-3-hydroxymethylcarbazo\e ..................... 177
8. 3-Formyl-7-hydroxycarbazole . . . . . . . . . . . . . . . . . . . . . . . . . . .. 177
9. O-Methylmukonal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 178
10. 3-Formyl-6-methoxycarbazole ........................... 178
11. 7-Methoxymukonal .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 178
 Contents VII

12. Clausenal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179

13. 6-Methoxymurrayanine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179
14. 7-Methoxy-O-methylmukonal . . . . . . . . . . . . . . . . . . . . . . . . . . . . 180
IS. Murrayaline C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 180
16. Carbazole-3-carboxylic Acid . . . . . . . . . . . . . . . . . . . . . . . . . . . . 180
17. 3-Carbomethoxycarbazole . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 180
18. Clauszoline C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181
19. 3-Carbomethoxy-6-methoxycarbazole . . . . . . . . . . . . . . . . . . . . . . 181
20. Clauszoline I . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181
21. Clauszoline J ...................................... . 182
22. Clauszoline K . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182
23. Clauszoline L ...................................... . 183
24. Clauszoline M . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183
ii) C l8 -Alkaloids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183
I. Clauszoline B ...................................... . 183
2. Clauszoline D ...................................... . 184
3. Euchrestine A . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 184
4. Eustofoline D ...................................... . 185
5. Furostifoline . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185
6. Glycomaurine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185
7. Glycomaurol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 186
8. 7-Methoxyheptaphylline . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 186
9. 7-Methoxymurrayacine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187
10. Murrayamine A . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187
II. Pyrayafoline B ..................................... . 188
12. Pyrayafoline C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 188
13. Mukoenine A . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189
14. Mukoenine C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189
IS. Murrayaquinone E . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189
16. Clauszoline H ...................................... . 190
iii) C 23 -Alkaloids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 190
I. Clauszoline A . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 190
2. Clauszoline F . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
3. Euchrestine B ...................................... . 191
4. Euchrestine C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192
5. Euchrestine D ...................................... . 192
6. Euchrestine E 193
7. Eustifoline B ...................................... . 193
8. Eustifoline C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193
9. Isomahanine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 194
10. (+ )-Mahanine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 194
II. Murrayaline D ..................................... . 195
12. Murrayamine B .................................... . 195
13. Murrayamine C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 196
14. Murrayanol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 196
15. Pyrayafoline D ..................................... . 197
16. Murrayaquinone C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197
17. Murrayaquinone D .................................. . 197
18. Pyrayafoline E . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 198
19. Mukoenine B . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 198
VIII Contents

iv) Dimeric Carbazole Alkaloids from Higher Plants ................ . 199

a) C26 -Alkaloids ....................................... . 199
I. Indole Dimer ................................... . 199
2. Bis-2-hydroxy-3-methylcarbazole ..................... . 200
3. Bismurrayaquinone A ............................. . 200
4. Chrestifoline A .................................. . 201
S. Cherestifoline D 201
6. Murrastifoline A 202
7. Murrastifoline B 202
8. Murrastifoline F ................................. . 203
b) C31 -Alkaloids ....................................... . 203
I. Chrestifoline B .................................. . 203
2. Murrafoline G . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204
3. Murrastifoline D ................................. . 204
4. Murrastifoline E ................................. . 205
c) CwAlkaloids ....................................... . 206
I. Chrestifoline C .................................. . 206
2. Murrafoline H ................................... . 206
3. Murrastifoline C ................................. . 207
4. Bis-7-hydroxygirinimbine A ......................... . 208
S. Bis-7-hydroxygirinimbine B ......................... . 208
6. Murranimbine ................................... . 208
d) C46 -Alkaloids ....................................... . 210
I. Bismahanine .................................... . 210
2. Bismurrayafoline C ............................... . 210
3. Bismurrayafoline D ............................... . 211
B. Alkaloids from Lower Plants .............................. . 211
i) Alkaloids from Microbial Sources ......................... . 212
a) Alkaloids Built on a Carbazole Skeleton .................... . 212
I. Aflavazole ..................................... . 212
2. Carazostatin .................................... . 213
3. Carquinostatin A ................................. . 213
b) Indolocarbazoles .................................... . 214
i) Alkaloids Built on an Indolocarbazole Skeleton
(Two Nitrogens) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 214
1. Antitumor Compound AT 2433 AI ..................... 214
2. Antitumor Compound AT 2433 A2 ..................... 21 S
3. Antitumor Compound AT 2433 BI ..................... 21S
4. Antitumor Compound AT 2433 B2 ..................... 21S
5. Arcyriaflavin B ................................... 216
6. Arcyriaflavin C ................................... 216
7. Protein Kinase C Inhibitor K-252a . . . . . . . . . . . . . . . . . . . . .. 217
8. Protein Kinase C Inhibitor K-252b ..................... 217
9. Protein Kinase C Inhibitor K-252c . . . . . . . . . . . . . . . . . . . . .. 218
10. Protein Kinase C Inhibitor K-252d ..................... 218
II. Rebeccamycin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 219
12. Staurosporine .................................... 219
13. Tan 1030 A ..................................... 220
14. Tan 999 ........................................ 221
15. UCN-Ol ........................................ 222
 Contents IX

ii) Alkaloids from Marine Sources ........................... 222

I. I-Methylcarbazole . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 222
2. I-Acetylcarbazole ................................. 223
3. Aldose Reductase Inhibitors .......................... 223
References 224

Author Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 231

Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 245
 List of Contributors

Chakraborty, Prof. Dr. D. P. t, Institute of Natural Products, Satchasi Para Lane, Calcutta
700 036, India

Krohn, Prof. Dr. K., Fachbereich Chemie und Chemietechnik der Universitat Paderborn,
Warburger Str. 100, D-3309S Paderborn, Germany, e-mail: [email protected].
de

Messner, Prof. Dr. P., Zentrum fUr Ultrastrukturforschung und Ludwig Boltzmann Institut
fUr Molekulare Nanotechnologie, Universitat fUr Bodenkultur Wien, Gregor-Mendel-
Str. 33, A-IISO Wien, Austria, e-mail: [email protected]

Roy, Dr. S., S, lagadishnath Roy Lane, Calcutta 700 006, India, e-mail: shyamaliroy@
yahoo.com

Schaffer, Dr. C., Zentrum fiir Ultrastrukturforschung und Ludwig Boltzmann Institut fUr
Molekulare Nanotechnologie, Universitat fUr Bodenkultur Wien, Gregor-Mendel-Str.
33, A-lISO Wien, e-mail: [email protected]
 Natural Products Derived from Naphthalenoid
Precursors by Oxidative Dimerization
K. Krohn
Fachbereich Chemie und Chemietechnik,
Universitat Paderbom, Germany

Contents

I. Introduction
2. Isolation and Structure Elucidation .............................. 3
2.1. Spirobisnaphthalenes with Two Oxygen Bridges . . . . . . . . . . . . . . . . . . 3
2.2. Spirobisnaphthalenes with Three Oxygen Bridges (Preussomerins) . . . . . 21
2.3. Spirobisnaphthalenes with Two Oxygen Bridges and One C-C
Bridge (Spiroxins) ...................................... 25
2.4. Determination of Relative and Absolute Stereochemistry . . . . . . . . . . .. 26
3. Biological Activity ......................................... 29
4. Biosynthesis .............................................. 30
5. Synthesis ................................................ 34
5.1. Biomimetic Type Approach .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
5.2. Spiroketalization Approach ................................ 39
Acknowledgements ........................................... 46
References ................................................. 46

1. Introduction

In the last decade, a structurally diverse class of new bioactive

natural products was isolated from fungi in which two naphthalene units
are fused together via oxidative coupling. These compounds attracted
attention because of their antifungal, antibacterial, and antitumoral
2 K. Krohn

activity. In addition, several enzymes, namely: phospholipase D, DNA

gyrase, and Ras famesyl-protein transferase, were also found to be
inhibited with high selectivity.
It has been known for a long time that nature can dimerize simple
naphthalene building blocks through one or more C-C bonds to construct
a variety of secondary metabolites. Examples for these compounds
include the neopodine glycosides (1), the sphaerolones (2), the
stemphytriols (1), and the stemphyltoxins (3). More highly substituted
compounds of this class are represented in the perylenequinones (4, 5) as
exemplified by the elsinochromenes (6) (for a review on some C-C-
dimeric naphthalenes see Gill and Steglich in (7». The biosynthetic
origin of this type of naphthalene "dimers" is well established (see for
example (8».
In this overview, we will focus on the more recently elucidated
structures where the naphthalene units are linked by two or three oxygen
atoms. In most of these "dimers" the naphthalene cores are partially
modified (saturated or oxidized) and the oxygen atoms are also
incorporated into the acetal bridges. As one naphthalene part is
generally linked to a decalin system via a spiroketal bridge, this class
of compounds is referred to as "spirobisnaphthalenes" (9), or, more
specifically, "bisnaphthospiroketals" in case of the spiroxins, (10) or
"spiroacetal-linked naphthodiepoxydecalinones" in case of the diepox-
ins (11). Reflecting on the relatively small number of carbon atoms, the
spirobisnaphthalene type of natural products belong one of the most
diverse classes of secondary metabolites. They are an excellent example
of how flexible nature is in producing numerous diversified compounds
from relatively small building blocks (monomeric naphthols) by
employing a variety of simple chemical modifications like epoxidation,
reduction, methylation, oxidation, halogenation, etc.
Three different types of oxygen-bridged spirobisnaphthalenes have
thus far been isolated. Their molecular skeletons are represented in
Chart 1 by spiroxin A (1), with one carbon and two oxygen bridges (10);
palmarumycin CPl (2) (12), the parent compound of the spirobis-
naphthalenes with two oxygen bridges; and preussomerin A (3), where
the naphthalene units are linked over three oxygens, representing two
spiroacetal groups (13).
All existing data for the naturally occurring members of each
family of spirobisnaphthalenes are compiled in tables, in which the
synonyms used in the original publications are listed as well (e.g.
reference, source, melting point, specific optical rotation, CD/absolute
configuration, X-ray analysis, placement of formulae in Charts/Schemes,
and biological activity).
References, pp. 46-49
 Natural Products Derived from Naphthalenoid Precursors 3

OH OH

""90
0 OH
0 OH
CI
0"" 0"
11,/ " ~

o Q

63
0

OH 0
OH
Spiroxin A (1) Palmarumycin CP 1 (2) Preussomerin A (3)

Chart 1. The three molecular skeletons of spirobisnaphthalenes

2. Isolation and Structure Elucidation

2.1. Spirobisnaphthaienes with Two Oxygen Bridges

The first reported spirobisnaphthalene (with two oxygens in the

bridge) was the antibiotic MK 3018. It was the subject of a patent in
which structure 4 (Scheme 1) was tentatively assigned (14). However,
its relative or absolute stereochemistry has never been reported. The com-
pound was apparently isolated from the fungus Tetraploa aristata I R 25
and showed a broad spectrum of antibacterial activity. Unfortunately,
no similar or identical compound was subsequently isolated that could
have confirmed the details of the substitution pattern and assigned a
stereochemistry.
Shortly after this report, a metabolite called bipendensin (Sa) (m.p.
254°C) was isolated from the trunk wood of A/zelia bipendensis (15).
Despite the small amount of material available, its structure could be
elucidated with the aid of modem NMR techniques. In particular, two-
dimensional NMR proved to be useful to assign the signals for the
carbon atoms and protons to the two fragments A and B and corroborate
the connectivity of the carbon skeleton (Scheme 1). The dioxynaphtha-
lene fragment A showed the expected shifts for aromatic protons and
carbons. Notably, the two lowfield signals for C-l' and 8' at {j = 146.9
and 146.8 ppm in the 13C NMR spectrum were typical for aromatic
carbon atoms bonded to oxygen atoms. The most significant signal at
{j = 97.0 ppm in the 13C NMR spectrum of fragment B originated from
the acetal carbon. These signals are characteristic for all spirobis-
naphthalenes and mark a spectral feature that was common to all
spirobisnaphthalenes subsequently isolated from the culture broth of
4 K. Krohn

o::"M
OH OH

o/M
OH 0 OH OH

~
¥H
"XV o "~

J:rL
0
fragment B
o 0

~
MK 3018 (4)
~
~
~
Palmarumycin C 11 (5)

fragment A
PCC ~
o

o:;::Q:)
OH

R = H: Bipendensin (Sa)
J:rL
~
Palmarumycin C2 (6)
Sch 53823 Deoxypreussomerin A
R = CI: Sch 53825 (5b)

Scheme 1. Structure of MK 3018 (4), palmarumycin Cll (S), bipendensin and Sch 53823
(Sa), Sch 53825 (Sb) and PCC oxidation of palmarumycin Cll to palmarumyin C z (6)

fungal fermentations. The two fragments A and B of bipendensin can be

assembled to structure Sa. However, the relative stereochemistry of
bipendensin (Sa) currently remained unresolved because the observed
small coupling constant of J = 2.2 Hz between H-3 and H-4 did not
allow an unambiguous assignment. The author suggested that bipen-
densin is presumably derived from a naphthoquinone called juglone.
However, later investigations of the biosynthesis showed that 1,8-
dihydroxy-naphthalene (l,8-DHN) is the likely biosynthetic precursor
((16, 17, 18) vide infra). (Remark: as all of the other spirobisnaphtha-
lenes were isolated from fungi, we have to assume that compound S is
also produced by an endophytic fungus living in the tree Afzelia
bipendensis).
Later on, more complete data of this metabolite Sa were published
in a full paper (19). The spectroscopic data deviate from those of
palmarumycin ell (m.p. 237-238°C), a metabolite with the same gross
structure, isolated from Coniothyrium palmarum (16). The stereoche-
References, pp. 46-49
 Natural Products Derived from Naphthalenoid Precursors 5

mical relevant coupling constants in the 1H NMR spectrum of

bipendensin (Sa) for h4 = 2.2 Hz differ slightly from those of
palmarumycin Cll with h,4 = 2.7 Hz. The gross structure of palmar-
umycin Cll (5) was confirmed by oxidation with pyridinium
chlorochromate to palmarumycin C 2 (6) (Scheme 1) and its relative
stereochemistry was later confirmed by total synthesis (20). Chu et al.
(21) isolated a compound Sch 53823 of the same composition with a
nearly identical melting point (235-240°C) but with positive specific
optical rotation (see Table 1). The agreement of the physical and
spectroscopic data (notably the NMR spectra) suggests the identity of
Sch 53823 with bipendensin (Sa) and, based on reduction experiments,
Taylor et al. (20) suggested the anti-configuration Sa for bipendensin
and Sch 53823 and the syn-configuration for palmarumycin Cll (5).
Considering the NMR data, a chlorinated product Sch 53825 probably
also has the anti-configuration 5b. The stereochemical questions of
relative and absolute configuration have been resolved for a number of
spirobisnaphthalenes and will be discussed later (vide infra).
In the year 1993 and in subsequent years, five different research
groups from pharmaceutical industry as well as academy, including
our group at the university of Paderborn, and Zeeck et al. at Gottingen,
published a number of papers on the isolation, structure elucidation,
and biological activity of spirobisnaphthalenes that were related to
MK 3018 (4) or bipendensin (Sa). Some of the information was
originally communicated in patents (34) or as posters at meetings
(see Ref. 7 in (31)) and reported new secondary fungal metabolites
now known as spirobisnaphthalenes. These compounds were produced
by different fungi, were given different names, and their structural
formulae were drawn in different ways. We have now compiled their
synonyms and relevant data in Table 1 and combined them with the
formulae.
Schlingmann et al. at Lederle Laboratories (American Cyanamid
Company) investigated the metabolites of a non-sporulating fungus
isolated by MYCOsearch from a tree trunk growing in Panama. This
endophytic fungus, subsequently grown only as a mycelium sterilum,
also produced an antibiotic of the allenic poly acetylene family (35),
but the major metabolites were spirobisnaphthalenes named diepoxins
because they contained two epoxide groups at the decalin ring
system (24). The absolute stereochemistry of the diepoxins was
established later (vide infra) by employing the exciton coupled CD
method on some of their bis-dimethylaminobenzoate derivatives (11).
The formulae shown here reflect the absolute stereochemistry thus
determined.
 6 K. Krohn

Table 1. Naturally Occurring Spirobisnapthalenes. Source (organism), melting point, specific optical
rotation, absolute configuration, structural confirmation by X-ray analysis, and biological activity.
M.p. mostly decomposition
Name Ref. Source M.p. [(fID X-ray CD/abs. Schemel Bioactivity
°C conf. Chart

MK 3018 (14) retraploa S I Broad anti-

(4) aristata I R 25 bacterial
activity
Bipendensin (15, 19) Afzelia 254 S I not tested
(Sa) bipendensis
Palmarumycin Cll (16) Coniothyrium 237-238 -153 S I weakly
(5) palmarum antibacterial
Sch 50676, (23) N. mangiferae 235-238 -133.5 - S I, C 4 antitumor
identical
with p. Cll (5)
Sch 53823 (Sa) (21) Endophyte 235-240 +227 S I phospholipase
D inhibitor
Sch 53825 (5b) (21) Endophyte 182-183 +74 S I phospholipase
D inhibitor
Palmarumycin C 2 (16) C. palmarum 228 -341 + +(22) S I, C 4 antifungal,
(6) antibacterial
Diepoxin (f (7) (24) nonsporulating +30 + C2 antifungal,
fungus antibacterial
Diepoxin 7) (8) (11, 24) nonsporulating 250 +30, +(11) C 2, S 3 virtually
fungus +23 inactive
Palmarumycin C 14 (16) C. palmarum C 2, S 3 not tested
(8) (mixture with 9)
Sch 53516 (8) (25) N. mangiferae 270--272 C 2, S 3 phospholipase
D inhibitor
Sch 53517 (8a) (25) acetate of 8 120--122
Diepoxin ( (9) (11,24) nonsporulating +75 C 2, S 3 antifungal,
fungus antibacterial
Palmarumycin C 13 (16) C. palmarum C 2, S 3 not tested
(9)
Sch 53514 (9) (25) N. mang ife rae 152-154 C 2, S 3 antitumor,
phospholipase
D inhibitor
Sch 53515 (9a) (25) acetate of 9 225-227 phospholipase
D inhibitor
Cladospirone (26) Sphaeropsidales >160 + + C 2, S 3 antibacterial,
bisepoxide (9) sp. herbicidal
Diepoxin (Y (10) (24) mycelia sterila +67 + C 2, S 2
Sch 49209 (10) (27) N. mangiferae 144-146 +79.1 C2 antitumor
Acetate (lOa) (27) acetate of 10 S2 antitumor
Diepoxin 'I (11) (11) nonsporulating + + C3 antifungal,
fungus antibacterial
Diepoxin 6 (12) (11) nonsporulating 241 + C3 not tested
fungus
Diepoxin ¢ (13) (11) nonsporulating + C3 not tested
fungus
Palmarumycin (16) C. palmarum 236 C3 antifungal,
C IO (13) antibacterial
Diepoxin L (14) (11) derivative 242 + C3 not tested

References, pp. 46-49

 Natural Products Derived from Naphthalenoid Precursors 7

Table 1 (continued)

Name Ref. Source M.p. [alD X-ray CD/abs. Schemel Bioactivity

'C conf. Chart

Diepoxin K (15) (11) derivative 158; + + C3 not tested

232
Sch 50674 (16) (23) derivative 245-247 +33.1 + S2 antitumor
of 10
Sch 49210 (17) (25) N. mangiferae 140-143 reI. C4 PLD
inhibition
Sch 50673 (18) (23) N. mangiferae 164-166 -89.8 C4 antitumor
Sch 49211 (20) (28) N. mangiferae C4 PLD
inhibition
Sch 49212 (21) (28) N. mangiferae C4 PLD
inhibition
CJ-12, 371 (22) (29) fungus >265 -46.8 +1+ C5 Gyrase inh.
dec.
CJ-12, 372 (23) (29) fungus >238 -82.0 +1+ C5 Gyrase inh.
dec.
4-0xo- (30, 26, 3l)Spaeropsidales >200 S3 not tested
cladospirone- sp.
bisepoxide (25)
Cladospirone B (31) (9) S. sp. 230 -270 + + C6 not active
Cladospirone C (32) (9) S. sp. 164 -35 + C6 antibacterial
Cladospirone D (33) (9) S. sp. 127 +55 + C6 antibacterial,
herbicidal
Cladospirone E (34) (9) S. sp. 236 -217 + + C6 not active
Cladospirone F (35) (9) S. sp. 140 -150 + C6 not active
Cladospirone G (36) (9) S. sp. 135 +5 + C6 not active
Cladospirone H (37) (9) S. sp. 156 -22 + C6 not active
Cladospirone I (38) (9) S. sp. 138 +14.6 + C6 not active
(39) (9) derivative 68 +6.5 + C6 not tested
Palmarumycin CP j (12) C. palmarum 170 +1+ C I weakly
(2) dec. antibacterial,
antifungal
Palmarumycin CP2 (12) C. palmarum 170 C7 not active
(40) dec.
Deoxypreus- (32) coelomycetous C7 inactive
somerin B (40) fungus
Palmarumycin CP, (12) C. palmarum 190 -102.8 + +1+ (22)C 7 antibacterial,
(41) dec. antifungal
Palmarumycin CP4 (12) C. palmarum 193 +495 + C7 antibacterial,
(42) antifungal
Palmarumycin CP4. (33) C. palmarum 213 +70.6 + +1+ C7 nOllested
(43)
Palmarumycin CP, (33) C. palmarum 168 +45.5 + +1+ C7 not tested
(44)
Palmarumycin C j (16) Coniothyrium >180 C8 not tested
(45) sp.
Palmarumycin C 2 (16) C. sp. 228 -341 + +1+ S I antibacterial,
(6) antifungal
Deoxypreus- (32) unidentified 235-236 -300 S I not tested
somerin A (6) coelomycetes
Palmarumycin C, (16) C. sp. 220 -300 + C8 antibacterial,
(46) CHCI, antifungal
 8 K. Krohn

Table 1 (continued)
Name Ref. Source M.p. [alD X-ray CD/abs. Schemel Bioactivity
°C conf. Chart

Palmarumycin C4 (16) C. sp. (S4) -2S5.5 - CS antibacterial.

(47) antifungal
Palmarumycin C5 (16) C. sp. 170 + CS not tested
(48)
Palmarumycin C6 (16) C. sp. 191-192 - CS not active
(49)
Palmarumycin C7 (16) C. sp. CS not tested
(50) mixture
with 51
Palmarumycin Cg (16) C. sp. CS not tested
(51)
Palmarumycin C9 (16) C. sp. +1+ CS antibacterial,
(52) (43) antifungal
Palmarumycin C IO (16) C. sp. 236 -4S.2 - +1+ C3 antibacterial,
(13) (43) antifungal
Palmarumycin Cll (16) C. sp. 237-23S -153 S 1 weakly
(5) antibacterial,
antifungal
Palmarumycin C 12 (16) C. sp. 207-20S -179.6 - +1+ CS antibacterial,
(53) (43) antifungal
Palmarumycin C!3 (16) C. sp. C2 not tested
(9) mixture
with 8
Palmarumycin C 14 (16) C. sp. C2 not tested
(8)
Palmarumycin C I5 (16) C. sp. 14S-149 -IS.1 CS antifungal
(54)
Palmarumycin C I6 (16) C. sp. IS7-ISS -43.3 - C4 not tested
(17)
Pre-palmarumycin (18) C. sp. 220 +43 + +1+ not tested
(75)
Palmarumycin C l7 (18) semisynthetic 17S +55°C - +1+ not tested
(76)

The first reported metabolites of this type were the diepoxins a (7),
TJ (8), ( (9), and a (10) (Chart 2) (24). The major component of the
antibiotic complex was diepoxin ( (9). The structure determination
relied mainly on HRMS and NMR spectra. Similarly as described for
bipendensin (Sa), two fragments related to A and B (Scheme 1) could be
discerned from the two-dimensional NMR spectra, notably the HMBC
spectra. Proton resonances at {j = 5.22, 3.58, and 3.55 ppm bonded to
carbon signals at {j = 61.7, 54.6, and 55.5ppm were typical for the
presence of epoxide groups. The quaternary carbon atoms at {j = 63.7
and 70.6 ppm formed the bridgeheads connecting the two fragments
by oxygen atoms. The fragments can only be combined as shown in
References, pp. 46-49