close

Вход

Забыли?

вход по аккаунту

?

Natural Fecapentaene-14 and One Fecapentaene-12 Component are all-trans Stereoisomers.

код для вставкиСкачать
(1986) 3040; k) Y. Ito, Y. Amino, M. Nakatsuka, T. Saegusa, rhid. I05
(1983) 1586: Rebuttal: J. L. Charlton, Can. J Chem. 54 (1986)720; I ) D.
A Evans, K. T. Chapman, J. Bisaha, J. Am. Chem Soc 106 (1984) 4261;
m) D A. Evans, K. T. Chapman. J . Bisaha, Tetrahedron Lerr 25 (1984)
407
I.
131 a ) J. K. Whitsell. A. Battacharya, D. A. Aguilar, K. Henke, J. Chem. Soc.
Cliem. Commun. 1982. 989; b) J. K. Whitesell, D. Deyo, A. Battacharya,
ihd. 1983. 802; c) J. K. Whitesell, J . N. Younathan, J. R. Hurst, M. A.
Fox, J . O r g Chem. 50 (1985) 5499; d ) J. K. Whitesell, Arc. Chem. Res. 18
( 1985) 280; e) J. K. Whitesell. R. M. Lawrence, H. H. Chen, J . Orq. Chem.
51 (1986) 4779; f ) W. Oppolzer, C. Robbiani, K. Battig, Hefu. Chrm. Acra
63 (1980) 2015; g) W. Oppolzer, Pure. Appl. Chem. 53 (1981) 1181.
141 a ) G. L Lange, M . Lee, Tetrahedron Lerr. 25 (1985) 6163; b) H. Herzog,
H. Koch, H.-D. Scharf, J. Runsink, Tetrahedron 42 (1986) 3547.
[5] J . d'Angelo, J. Maddaluno, J . Am. Chem. Suc. 108 (1986) 81 12.
IS] P. Binger, A. Brinkmann, J. Richter, Tetrahedron Lett. 24 (1983) 3599.
[7] J Kallmerton, T. 1. Could, J. Orq. Chem. 51 (1986) 1152.
[XI a ) J. K Whitesell. A. Bhattacharya, K. Henke, J . Chem. Soc. Chem.
Ctrmrnun. IY82, 988; b) Y. Yamamoto, H. Yatagai, Y . Ishihara, N. Maeda, K. Maruyama, Terrahedron 40 (1984) 2239; c) P. Crossen, P. Herold,
P. Mohr. C. Tamm, Helc. Chim.Acta 57 (1984) 1625
[9] D. A. Evans. M. D. Ennis, D. J . Mathre, J . Am. Chem. Soc. 104 (1982)
1737.
[lo] The diastereoselectivity of the cycloaddition of crotonate If bearing the
4-rerr-butyl substituent was beyond the limits of our capillary VPC detection and could not be used for these comparisons.
[I11 J. Rebek, B. Askew, D. Nemerh, K. Parris, J. Am. Chem. Soc. 109(1987)
2432.
Fig. I . a) HPLC profiles of fecapentaene fractions from human feces.
A, B, C : fecapentaene-12 isomers; D : fecapentaene-14 isomer. b) HPLC
absorption at 340 nm.
profiles of the synthetic fecapentaenes 3 and 4. AAaO:
25 cm x 4.6 mm;
mobile
phase:
Column:
Ultrasphere
ODS,
CH3CN :CH,OH : H 2 0 :tetrahydrofuran 36.2 :25.4 :32.0 :6.4; diode array
detector LKB, model 2140.
Natural Fecapentaene-14 and One Fecapentaene-12
Component are all-trans Stereoisomers**
By Jost? Baptisfa, Jiri J. Krepinsky,* and
Hans Rudolf Pfaendler*
Fecapentaenes are very effective, directly acting mutagens present in the feces of a large section of European and
North American communities, and are suspected of being
colon carcinogens."' Their structures were elucidated recently as 1 and 2.[2.31The absolute configuration of the
single chiral center has been determined to be S,l4]but the
full geometry of the large, conjugated double bond system
allowing 32 stereoisomers (excluding enantiomers) has
thus far remained unclear. Only the trans configuration
CH2O-CH=CH-CH=CH-CH=CH-CH=CH-CH=CH-(CHH~
I
CHOH
I
1 ,
n = l
2 ,
n = 3
CH20H
H
CH20H
H
3 ,
H
H
H
n = l
4 , n = 3
[*I
[**I
Prof. Dr. J. J. Krepinsky, Dr. J. Baptista
Ludwig Institute for Cancer Research, Toronto Branch
Toronto, Ontario M4Y 1M4 (Canada) and
Departments of Medical Genetics and Biophysics
University of Toronto
Toronto, Ontario M5S 1A8 (Canada)
Prof. Dr. H. R. Pfdendler
lnstitut fur Organische Chemie der Universitat
Karlstrasse 23, D-8000 Munchen 2 (FRG)
The synthetic part of this work was financially supported by the
Deutache Forschungsgemeinschaft and the Fonds der Chemischen Industrie.
1 I86
0 VCH Verlaqsye.~eN.~clia~r
mbH. 0-6940 Weinheim. 1987
of the CC double bond adjacent to the glyceryl moiety
could be deduced from the H-NMR coupling constant
(12 Hz) of the isolated 0-CH=CHsignal (6=6.84
in [D,]DMF.[2.31
Our investigation of many fecal samples by HPLC revealed the occurrence of three fecapentaene- 12 isomers (cf.
Fig. l a , peaks A, B, and C). In contrast fecapentaene-14
exists in only one geometric form (Fig. la, peak D). The
ratio of the components can vary considerably from sample to sample depending on the donors.
The fecapentaenes are very unstable compounds; the
mixture of fecapentaenes-12 could not be separated on a
preparative scale. However, the three components, corresponding to the peaks A, B, and C in Figure l a , were
shown to have the same CI mass spectrum using a combined HPLC-mass spectrum unit. Thus, it became evident,
that they were true stereoisomers. However, the exact identification of the isomers was not possible.
Fecapentaene-14 (peak D in Fig. la) is isomerically
pure. Nevertheless, the geometry of its double bonds could
not be defined because of the complexity of the olefin H
signals in the 'H-NMR spectrum."' Fecapentaene- I4 is
even less stable than the fecapentaenes-12 and the spectrum of the natural material was always adversely affected
by decomposition products.
Through the total synthesis of crystalline, racemic allfrans-fecapentaene-12"l and -14@'it became possible for
the first time to compare synthetic and natural materials
and thus to clarify which natural products, if any, are alltrans. The HPLC system used for the separation of fecal
samples was also suitable for making a comparison of
these materials.
A mixture of fecapentaenes from feces was freshly prepared using a procedure previously described in the literaturefZJ(for HPL chromatogram, see Fig. la). Synthetic alltrans-fecapentaene-12 (3) (cf. Fig. Ib) showed exactly the
same retention time as the component C of the fecapentaenes-12 and also co-eluted with it. The UV spectrum of
the component C (recorded with the diode array detector)
and the UV spectrum of 3 were likewise identical. This
proves that the component C is all-truns-fecapentaene-I2
(3).
Similarly, synthetic all-trans-fecapentaene- 14 (4) (cf.
HPL chromatogram, Fig. Ib) exhibited identical retention
time as the component D , and both co-eluted. The H-
0570-0833/87/1 I 11-1 186 $ 02.50/0
Anqew. Chem. Int. Ed. Engl. 26 (1987) No I I
NMR spectra (in [D],DMF) of natural D and synthetic 4
were essentially identical, particularly in the region representing olefinic protons (6 = 5.6-6.8). This, in turn, proves
that the the component D is pure all-trans-fecapentaene14 (4).
We have also established that the CI mass spectra of the
natural and the synthetic compounds are identical. These
spectra, however, show very little fragmentation, and thus
are not sufficiently informative.
These investigations enable us for the first time to assign
the complete structural formulas to two naturally occurring fecapentaenes. The geometry of the CC double bonds
may play a role in the degree of mutagenicity exhibited by
both types of fecapentaene~.''.~~
Interestingly, the two identified components, all-trans-fecapentaene-12(3)[91
and alltrans-fecapentaene- I4 (4)['] belong to the most potent mutagens so far known. Their occurrence in human feces and
their accessibility by chemical synthesis raise hopes that
they might serve to answer the question whether the fecapentanes are carcinogens.
Received: July I , 1987 [Z 2322 IE]
German version: Angew. Chem. 99 (1987) 1183
[I] W. R. Bruce, A. J Varghese, R. Furrer, P. C. Land in H. N. Hiatt, J. D.
Watson, J. A. Winsten (Eds.): Origins of Human Cancer. Cold Spring
Harbor Laboratory, Cold Spring Harbor, NY, 1977,~.1641.
[2] a) I. Gupta, J. Baptista, W. R. Bruce, C. T. Che, R. Furrer, J. S. Gingerich,
A. A. Grey, L. Mardi, P. Yates, J . J. Krepinsky, Biochemistry 22 (1983)
241; b) W. R. Bruce, J. Baptista, T. Che, R. Furrer, J. S . Gingerich, 1.
Guptd, J. J. Krepinsky, A. A. Grey, P. Yates, Naturwissenschafen 69
(1982) 557.
[3] N. Hirai, 1). G. I. Kingston, R. L. Van Tassel, T. D. Wilkins, J . Am. Chem.
Soc. 104 (1982) 6149.
[4] N. Hirai, I>. G. 1. Kingston, R. L. Van Tassel, T. D. Wilkins, J. Nut. Prod.
48 (1985) 622.
IS] H. R. Pfaendler, F. K. Maier, S. Klar, J . Am. Chem. Soc. 108 (1986)
1338.
[6] H. R. Pfaendler, F. K. Maier, S. Klar, unpublished.
171 1. Gupta, K. Suzuki, W. R. Bruce, J. J. Krepinsky, P. Yates, Science
(Washington. DC) 225 (1984) 521.
[8] P. P. DeWit, M. van der Steeg, A. van der Gen, Tetrahedron Lett. 27
(1968) 6263.
[91 W. Goggelmann, F. K. Maier, H. R. Pfaendler, Mutation Res. 174 (1986)
165.
Lithium-Tellurium Exchange:
A New Entry to Organolithium Compounds**
By Tomoki Hiiro. Nobuaki Kambe, * Akiya Ogawa.
Noritaka Miyoshi, Shinji Murai, and Noboru Sonoda*
Since organolithium compounds,"] as well as Grignard
reagents, are most commonly used for the introduction of
carbon moiety into organic molecules, the development
of efficient methods for the synthesis of organolithium
compounds is of vital importance. Organolithium compounds can be prepared directly by hydrogen abstraction
or lithium-halogen exchange reaction; when these reactions fail, however, metal-metal exchange is widely resorted to.
We report here on a new method providing access to organolithium compounds 3 from organic tellurides 1 via
lithium-tellurium exchange. Alkyl-, benzyl- and allyl[*] Prof. Dr N. Sonoda, Dr. N. Karnbe, T. Hiiro, Dr. A. Ogawa,
Dr. N. Miyoshi, Dr. S. Murai
Department of Applied Chemistry, Faculty of Engineering
Osaka University
Suita, Osaka 565 (Japan)
[**I
This work was supported in part by a grant-in-aid from the Ministry of
Education, Science, and Culture, Japan.
Angew. Chem In1 Ed. Engl. 26 11987) No. I 1
lithium compounds can be synthesized in a one-pot
operation from halides without isolation of the tellurides
[see Reaction (c)].
Diorganotellurides 1 react with butyllithium at - 78 "C
in T H F to give the more stable organolithium compounds
3, which are subsequently trapped with benzaldehyde to
give the alcohols 4. In this way several types of organolithium compounds can be obtained in good yields [Reaction (a), see Table 11. (3-Phenyl styryl telluride l c afforded
exclusively the (2)-olefin 4c. It should be noted that benzyloxymethyllithium 3e and trimethylsilylmethyllithium 3f
are synthetically useful as alkoxymethylating"' and silylmethylatir~g'~]
reagents, respectively.
R3
= nBu
When the telluride 1 and the alkyllithium 2 are allowed
to react in the ratio 1 :2, both organic groups on the tellurium are converted into carbanions. For example, reaction
of 1 mmol of dibutyl telluride l h with 2 mmol of sec-butyllithium affords 1.73 mmol of the adduct 4h [Reaction (b),
see Table 11. This result suggests that the method described
here is even suitable for the preparation of nonstabilized
carbanions. Phenyllithium 3b can be generated under
identical conditions using n - or rerf-butyllithium.
Since alkyl aryl and dialkyl tellurides are readily accessible by reaction of lithium tellurolates 614]with alkyl halides 5 , we then attempted a one-pot synthesis of the organolithium compounds 3 from the corresponding halides
without isolation of the tellurides 1 [Reaction (c), see Table 11. With benzyl, allyl and alkyl halides as starting materials, we obtained the products 4a, 4i and 4j in good
yields. When methyl vinyl ketone was used as an electroR'X
+
R2TeLi
6
5
+
[R'TeR2]
- Lix
1
R3U
2
- RqeR2
(c>
OH
PhCHO
[R'LI]
HQ 'RlAI'h
3
4
Table I. Lithium-tellurium exchange; reaction types (a)-(c). For conditions
see Experimental procedure.
Type
R'
R'
R'
X
Reaction
Yield
"%I
~~
(a)
(a)
(a)
(a)
(a)
(a)
(b)
(b)
(b)
(c)
(c)
(c)
PhCH?
Ph
PhCH=CH(Z)
PhC4
PhCH20CH2
Me3SiCH2
Ph
Ph
nBu
PhCH2
CH,=CHCH-,
nPr
0 VCH Verlagsgesellschaft mbH. 0-6940 Weinheim. 1987
nBu
nPr
Ph
Ph
nBu
nBu
Ph
Ph
nBu
Ph
Ph
sBu
nBu
nBu
nBu
nBu
nBu
nBu
nBu
tBu
sBu
Ph
Ph
sBu
-
Br
Br
I
la-4a
lb-4b
lc-4c
Id-4d
le-4e
lf-4f
lg-4b
lg-4b
lh-4h
5a-4a
5i-4i
5j-4j
0S70-0833/87/1111-1187$ 02.50/0
74
77
89
89
66
89
80
72
86
72
96
84
I187
Документ
Категория
Без категории
Просмотров
0
Размер файла
235 Кб
Теги
stereoisomeric, one, natural, components, fecapentaene, transp
1/--страниц
Пожаловаться на содержимое документа