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Cercosporin a Singlet Oxygen Generator.

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1): apparently, 2a is not reactive enough. Formation of the
desired isomer 3 dominated over that of 4 by the ratio
4 :1. The same ratio of isomers was obtained with zinc
chl~ride-ether[~"'
(No. 2); although this reaction was carried out at -4O"C, some of the product decomposed at
longer reaction times. We therefore activated the allylic alcohol by trifluoroacetylation to afford 2b and found that
prenylation was feasible in refluxing dichloromethane
(No. 3). Interestingly, on lowering the temperature to 25°C
prenylation was more regioselective; formation of 3 was
preferred still more (3 :4 = 89 : 11; No. 4). The total isolated yield of 3 4 was 73%. Products arising from attack
of the tertiary allylic terminus on l a were not detected.
We found, however, that tertiary alkyl groups can be introduced into furans by a different method, i. e. by reaction
with 4-methyl-2-0~0-3-pentenenitrile
5['] in the presence of
aluminum chloride in benzene (Scheme 1). This reagent is
+
R
2) MeOH
la: R
Ib: R
Me
= H
=
R
6a: R
6b: R
R
=
M e (37%)
=
H (43%)
7a: R
+ CX30&OCH3
= M e (2.4%)
8a:
8b: R
=H
M e (10%)
(19%)
1971, 2251; c) P. G. Wiering, H. Steinberg, Th. J. de Boer, Rec. Trau.
Chim. Pays Bas 96 (1977) 119.
[4l a) H. M. R. Hoffmann, J. Matthei, Chem. Ber. 113 (1980) 3837; b ) R.
Henning, H. M. R. Hoffmann, Tetrahedron Lett. 23 (1982) 2305; c) H. M.
R. Hoffmann, R. Henning, Helu. Chim. Acta. 66 (1983) 828.
[5] a) Cf. also H. Klein, A. Erbe, H. Mayr, Angew. Chem. 94 (1982) 63; Angew. Chem. Int. Ed. Engl. 21 (1982) 82; Angew. Chem. Suppl. 1982, 105;
b) M. T. Reetz, ibid. 94 (1982) 97; 21 (1982) 96 and references cited therein.
[7] a) Cf. H. M. R. Hoffmann, K. Haase, Z. M. Ismail, S. Preftitsi, A. Weber,
Chem. Ber. 115 (1982) 3880; b) 2. M. Ismail, H. M. R. Hoffmann, Angew.
Chem. 94 (1982) 862; Angew. Chem. Int. Ed. Engl. 21 (1982) 859; Angew.
Chem. Suppl. 1982. 1819; c) A. Jellal, M. Santelli, Tetrahedron Lett. 21
(1980) 4487.
[81 J. E. Fitzpatrick, D. J. Milner, P. White, Synth. Commun. 12 (1982) 489;
D. N. Munro, D. J. Milner, Chem. Ind. (London) 1982, 603.
Cercosporin, a Singlet Oxygen Generator**
By Diane C. Dobrowolski and Christopher S . Foote*
Dedicated to Pro$ Giinther 0. Schenck on the occasion
of his 70th birthday
The photodynamic fungal pigment cercosporin 1['] is a
nonspecific toxin which kills plant cells in vitro in the presence of light by lipid p e r o x i d a t i ~ n [ ~The
, ~ ~ ]requirement
.
for light, the cercosporin-sensitized formation of the characteristic '0, oxidation product of cholesterol (the 5a-hydroperoxide), and the inhibition of the effects of cercosporin by /%carotene and other '0, quenchers suggest that the
mechanism of action involves production of '02sensitized
by lC9.
We now report direct evidence for '0, formation
by observation of the characteristic '0,-luminescence at
1270 nm sensitized by cercosporin. This is the first time
that a plant photodynamic sensitizer has been shown unequivocally to produce singlet oxygen. The quantum yield
of 'Oz formation is large: 0.81 f0.07 (95% confidence level).
Scheme 1. Tertiary alkylation of la, b with 4-methyl-2-0~0-3-pentenenitrile5
in the presence of AIC13.
more regioselective than the prenylation reagent; the ratio
6a :7a was 94 :6. Compound 6a, which is of the cis-jasmone type, has an interesting herbal, sweet, floral odor. 6a
and 6b have also been reduced to the corresponding alcohols 9a and 9b.
I
I
R
6a,b
%H
9a: R
9b: R
=
Me
=
H
1
YHz
COOCH,
CHz
H,COO&
2
R=CH>CHOHCH,
The introduction of functionalized tertiary alkyl groups
into furans by our second procedure goes beyond the recently described introduction of the simple t-butyl group['].
Clearly, decomposition and polymerization need no longer
be the necessary result of electrophilic alkylations of furans such as la, b. Finally, regioselective control has been
achieved both with respect to the site of attack in furan
and also with respect to the ambident electrophile.
Received: April 29, 1983 [Z 370 IEI
German version: Angew. Chem. 95 (1983) 737
The complete manuscript of this communication appears in:
Angew. Chem. Suppl. 1983. 985-993
Samples of 1 ( 1 . 0 ~
10-4M,A532= 1.25) or meso-porphyrin IX dimethyl ester 2 ( 3 . 0 ~1 0 - 4 ~A532=
,
1.15) in C6D6
were irradiated with a Nd :YAG laser (A = 532 nm)l6l. Luminescence was detected with a germanium p h ~ t o d i o d e ~ ~ ~ .
The luminescence intensity at 1270 nm was the same in air
or oxygen for both sensitizers, indicating that triplet states
alone are involved in '0, formation. The lifetime of the luminescence at 1270 nm (617 ps) and its quenching on addiI*] Prof. C.
["I
121 H. M. R. Hoffmann, N. F. Janes, J. Chem. SOC.C 1969, 1456.
131 a) P. H. Boyle, J. H. Coy, H. N. Dobbs, J. Chem. SOC. Perkin Trans. I
1972, 1617; b) M. Elliott, N. F. Janes, B. C. Pearson, J. Chem. SOC. C
720
0 Verlag Chemie GmbH, 6940 Weinheim, I983
S. Foote, Ms. D. C. Dobrowolski
Department of Chemistry and Biochemistry
University of California
Los Angeles, CA 90024 (USA)
Chemistry of Singlet Oxygen, Part 46. This work was supported by NSF
grant C H E 80-20 140. We thank Dr. M.E. Daub for helpful discussions
and a sample of cercosporin.-Part 45: J.-J. Liang, C.-L. Gu, M. L.
Kacher, C. S. Foote, J . Am. Chem. SOC.105 (1983) 4717.
0570-0833/83/0909-0720 $ 0 2 . 5 0 / 0
Angew. Chem. Int. Ed. Engl. 22 (1983) No. 9
tion of 2,3-dimethyl-2-butene further confirmed its identity
as lo2.
After correction for differing sensitizer optical densities,
the maximum intensities of 1- and 2-sensitized '02luminescence were compared. Since the quantum yield of triplet formation from 2 is 0.81[51,and this state is efficiently
quenched by oxygen to form 'Oz[51,
the absolute quantum
yield of cercosporin-sensitized formation of 'Oz could be
determined. Based on four independent determinations,
the relative ratio of luminescence produced from 2 to that
produced from 1 was found to be 1.01f0.04. Two separate determinations of the relative rates of photooxygenation of 2-methyl-2-pentene in benzene sensitized by 2 and
1 gave the ratio 1.00-+0.12. Both ratios indicate that the
quantum yield of formation of '02 sensitized by 1 is
0.81 f 0.07.
This large quantum yield strongly supports the suggestion that singlet oxygen is the toxic agent in host plants.
This is a striking example of the use of a chemical mechanism by a parasite to gain an "environmental advantage".
tion of the rings A and C in 13 could be confirmed by an
X-ray structure analysis.
+
Received: April 26, 1983;
revised: July 12, 1983 [Z 358 IE]
German version: Angew. Chem. 95 (1983) 729
111 S. Yamazaki, T. Ogawa, Agr. Biol. Chem. 36 (1972) 1707; R. J. J. C. Lonsberg, U. Weiss, C. A. Salemink, A. Amone, L. Merlini, G. Nasini, Chem.
Commun. 1971, 1463.
121 M. E. Daub, Plan$ Physiol. 69 (1982) 1361.
[3] a) M. E. Daub, Phytoparhology 72 (1982) 370; b) M. E. Daub, personal
communication.
[4] a) P. R. Ogilby, C. S. Foote, J. Am. Chem. Sac. 104 (1982) 2069; b) ibid.
IOS (1983) 3423.
[S] R. Bonnett, A. A. Charalambides, E. J. Land, R. S. Sinclair, D. Tait, T. G.
Truscott, 3. Chem. Soc. Farad. Trans. I 76 (1980) 852.
[6] Cercosporin was provided by Dr. M.E. Daub, Michigan State University.
Its structure and purity were confirmed by comparison of the absorption
and NMR spectra with published data"'. 2-Methyl-2-pentene (Aldrich)
was purified by column chromatography on basic A1203.C6H6(Mallinckrodt) was distilled from P20, immediately before use. 2 (Sigma) and
C6H6(Cambridge Isotope Laboratories) were used as received.-The apparatus used to observe '02
luminescence has been described previously
141.
U
9
lh
[*I Dr. M. Demuth, Dr. A. Cbnovas, E. Weigt
Max-Planck-Institut fur Strahlenchemie
Stiftstrasse 34-36, D-4330 Mulheim a. d. Ruhr (Germany)
Prof. Dr. C. W g e r , Dr. Y.-H. Tsay (X-ray structure analysis)
Max-Planck-Institut fur Kohlenforschung
Kaiser-Wilhelm-Platz 1, D-4330 Mulheim a. d. Ruhr (Germany)
Angew. Chem. In!. Ed. Engl. 22 (1983) No. 9
-
. H
J
p
Hl
O
0
0
L
I
10
Synthesis and Structure of a Linearly anti-Annelated
Tetracycloundecane. A Potential Precursor for a
Coriolin Synthesis
By Martin Demuth*, Antonio Canovas, Eva Weigt,
Carl Kriiger, and Yi-Hung Tsay
Dedicated to Professor Giinther 0. Schenck on the
occasion of his 70th birthday
We recently presented a widely applicable concept for
the synthesis of cyclopentanoid natural products based on
the utilization of tricyclo[3.3.0.02~8]octan-3-one
1 as central
optically active building block"*21.Scheme 1 outlines the
strategy (AB + C principle) now chosen by us for the preparation of the tetracycloundecanes 9 and 12, which are
potential precursors for the synthesis of coriolins"'. The
most important step in the sequence involves the previously only indirectly dernon~trated~~'
anti-annelation of a
third five-membered ring to 1. The desired anti-configura-
ie
H
11
li
H
..
i
L
f
12
Scheme 1. a: NaH, Mel, tetrahydrofuran, SO "C. b: 3-chloro-2-methylpropene, KBr, tBuOK, tBuOH, toluene, 80°C. c: Os04, NalO.,, dioxane, HZO,
room temperature. d: Nafion-TMS (perfluorinated trimethylsilyl sulfonate
resin), toluene, 80°C. e: AcOAg, 12, toluene, room temperature. f: 1.5-diazabicyclo[4.3.0]non-5-ene, toluene, room temperature. g: tBuOK, tBuOH, toluene, 8 0 T , 5 min. h: as g but 12 h or TosOH cat., CH,OH, room temperature. i: iodotrimethylsilane, CHZCI2,room temperature. The numbering in
10-13 is that generally employed in coriolin chemistry.
The alkylation 2 + 3 proceeds in 86% yield and just as
selectively as the preceding methylation 1 + 2[2'31.Oxidative degradation (3+4 ; 82%) and subsequent isomerization 4+5 (60Y0)'~'afforded a suitable starting material for
further functionalization of ring A. The Prkvost addition of
acetyl hypoiodate to the double bond of 5 yields 6 and 7
with equally high selectivity (10 : 1) as has already been observed in an analogous case[',31.After re-formation of the
three-membered ring (6-8; 77%, annelation of the ring C
0 Veriag Chemie GmbH, 6940 Weinheim, 1983
0570-0833/83/0909-0721 $02.50/0
72 1
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