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Intermolecular CarbeneЦCarbene Coupling of a Nucleophilic Vinylidene and an Electrophilic 1-Methoxyethylidene Ligand.

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[I41 a) A. J. Gellman. Q Dai, J. Am. Chem. Soc. 1993. 115. 714-722; b) J. G .
Forbes, A. J. Gellman. hid. 1993. 115,6271-6283.
[15] H. Grabowska. W. Miita, L. Syper. J. Wrzyszcz, M. Zawadzkt. J. Curul., in
press
[16] K. Tanabe. T Ntshlzaki. in Proc. Int Congr. Carol. 6th 1976(1977). 863-871
[17] A. Kayo. T Yamaguchi, K. Tanabe. J. Cuful. 1983,83.99-106.
[I81 H. Grabowska. W. Kaczmarczyk, J Wrzyszcz, Appl. Cutul. 1989,47,351-355.
[19] C A. Towsend. L. M. Bloom, Terruhedron Lett. 1981, 22, 3923-3924.
[20] T. Kiimtkawa. I. Kubo. Swrhesis 1986, 431 -433.
[21] I . N. Godfrey. M. V. Sargent, J. A. Elix. J. Chem. Soc Perkin Truns. 11974, 7,
1353.1354
[22] J. Blackwell. W. J Hickinbottom. J. Cliern. Sot. 1961, 1405-1407.
Intermolecular Carbene - Carbene Coupling
of a Nucleophilic Vinylidene and an Electrophilic
1-Methoxyethylidene Ligand""
20 OC
6
[Cp,7i=C=CHz]
- CH4
i
X=Y
I X=Y
II
Cppi
7
5
X=Y :
H,C=CH,,
XEY:
R-C-C-R, NtC-R, PzC-R
O=C=CR2, O=C=NR, O=C=ML,
Treatment of [(CO),Cr=C(OCH,)CH,] (8) with 6 in n-hexane at a temperature between -30 and 25°C gives the new
heterodinuclear complexes 9 and 10 by an unusual coupling of
the Fischer-carbene complex 8 with the intermediate Schrockcarbene complex 5 . The C-C bond formation occurs between
carbon atoms of vinylidene, carbene, and carbonyl ligands. After chromatographic workup the separated complexes 9 and 10
can be isolated as air-stable red crystals. Cycloaddition products
of type 7, for example those typical with metal carbonyls,[8c1
were not detected.
Riidiger Beckhaus,* Jiirgen Oster, Rhett Kempe, and
Anke Spannenberg
Dedicated to Professor Max Herberhold
on the occasion ofhis 60th birthday
The formation and cleavage of carbon-carbon bonds is one
of the basic problems in organometallic chemistry. Experimentally and theoretically intriguing are both intramolecular coupling of carbene ligands forming olefinic species (1 2) and the
possibility of breaking carbon-carbon double bonds in the coordination sphere of transition metals (2 +l).['-61 Examples
for intermolecular C-C coupling (3 --f 4) on a heterodinuclear
complex fragment are still unknown.[''
-
1
2
3
4
9
10
The constitution of 9 and 10 follows from NMR and IR
spectroscopic data. The carbene carbon atoms show typical resonances at 6 = 336.7 (9) and 328.0 (10). Characteristic differences can be noted for the substituents of the C = C bond and for
the Cr(CO), fragment. As a result of the change of configuration
at the exocyclic double bond, the methyl resonance shows a
remarkable shift from 6 =1.90 (9) to 2.89 (10) in the ' H N M R
spectra. The methoxy coordination is documented by the shift
of the OCH, carbon resonance to lower field (6 = 65.6 (9), 54.6
(10)). In the infrared spectra of 9 typical signals for a C,, symmetry are observed, whereas a C,, pattern can be detected for
the Cr(CO), fragment of 10.
The X-ray structure determination of 9 shows two symmetryindependent molecules (9, 9 ) in the asymmetric unit (Fig. 1,
Our investigations concerning the titanaallene species
(5), preferably generated by selective
[Cp:Ti=C=CH,]
methane elimination from [Cp:Ti(CH=CH,)CH,] (6)demonstrate the nucleophilic character of the 3-carbon atom in 5,
which is responsible for the regiochemistry observed in the
preparation of cycloaddition product 7'') and for the reactions
of 5 with electrophiles.18e.91Here we contrast the reactivity of 5
with that of a classical Fischer-type carbene complex exhibiting
an inverse M = C polarity.
[*I Priv.-Doz. Dr. R. Beckhaus. Dip1 -Chem. J. Oster
Institut fur Anorganische Chemie der Technischen Hochschule
Professor-Ptrlet-Strasse 1, D-52056 Aachen (Germany)
Fax' Int. code +(241)8888-288
e-mail: r.beckhaus(nac.rwth-aachen.de
Dr R Kempe. Dr. A. Spannenberg
Arbeitsgruppe Komplexkatalyse der Max-Pianck Gesellschaft an der Univers i l t Rostock (Germany)
[**I This work was supported by the Deutsche Forschungsgememschaft and the
Fonds der Chemischen Industrie. We thank Prof. Dr. G . E. Herberich for his
continuing Interest and Prof. Dr. U. Rosenthal and his co-workers for the
X-ray structure determination. Stimulating remarks from the referees are
gratefully acknowledged.
ilngekt,. Chem. Int.
Ed. Engl. 1996. 35, No. 13/f4
0 VCH
Fig. 1. Molecular crystal of9, selected distances [A] and angles [ ~(Cp(l)
]
and Cp(2)
represent the centers of the Cp* llgands of the titanocene fragment; in square
brackets values of 9'. Ti-Cp(1) 2.105 [2.114], Ti-Cp(2) 2 090 [2.108], Ti-CS
2.202(7) [2.187(7)], T i - 0 5 2.002(5) [2.008(5)].05-C1 1.299(8) [1.288(8)]. C l - C 2
1.506(9) [1.465(9)], C5-C2 1.506(9) [1.527(8)], C2-C3 1.337(10) [I .325(9)], C3-C4
1.512(9) [1.483(9)]. C 3 - 0 6 1.381(8) [1.400(7)], 06-C6 1.470(9) [l 447(8)]. 0 6 - C r
2.204(5) [2.182(5)], C1-Crl 2.020(8) [2.025(8)]; C5-Ti-05 78 8(2) [80.1(2)]. Ti-05-
C1 125.8(4) [122.6(4)J, 05-CI-C2 110.1(7}[113.4(6)), CS-C2-C1 118.4(7)[118.2(6)],
C6-06-C3 121.2(6) [119.1(6)], C4-C3-06 116.6(7) [118.1(7)].
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data for 9 are given in brackets).[''l The formation of a chelate
ring by OCH, coordination leads to a distortion of the octahedral symmetry at the chromium center. Noteworthy in this connection is a small 06-Cr-C1 angle of 76.1(3)". The Cr-06 distance of 2.204(5) [2.182(5)] 8, is similar to that of bonds in
anisyl-carbene complexes1"] and significantly longer than the
A Cr-C1 disC r - 0 bond in [(CO),Cr(thf)] (2.123(3) 8,).[121
tance of 2.020(8) [2.025(8)] 8, can be related to short carbene
bonds;1131acyl resonance
for 9 can be neglected. In
agreement with this, a C1-05 distance of 3.299(8) [1.288(8)J8,
is found. The planes of the bicyclic system are almost coplanar
(max. deviation ~ 0 . 0 A).
6
The formation of the reaction products 9 and 10 is in accordance with a carbene-carbene coupling via the intermediate
allene complex 12.["] This reaction step can be explained by the
1
+co
Experimental Procedure
9 and 10: To a solution of 6 (280 mg, 0.778 mmol) in n-hexane (40 mL) was added
8 (140 mg (0.560 mmol) [18] at -30°C. After warming to room temperature the
reaction mixture was stirred for 3 h. The color changed from yellow to red, and 9/10
was obtained as a red-brown precipitate. The solid was dissolved in CH,CI, (3 mL)
and chromatographed on alumina (neutral. 100-125 mesh). With n-hexane a yellow solution of unchanged 8 was obtained. Elution with CH,Cl,/n-hexane (3/1)
produced a red solution of 10. After further elution with tetrahydrofuran a red
solution of 9 can be separated. The volume of the solvent was reduced to 2 mL in
VBCUO.
Addition of n-hexane (10 mL) gave 9 and 10 as red solids. Crystallization
from benzene afforded red crystals of the products.
9: Red crystals. yield 90 mg. 27 %. correct elemental analysis. IR (KBr). i. = 1987 s.
1873 sh. 1865 vs, 1821 s (CO), 1341 cm-l s. IR (CH,CI,): C =1994s, 1878 vs, 1828
s. 1343cm-'s.'HNMR(CDCI,,500MHz.25-C).6
=1.87(s,2H.CH2),1.90(s.
3H, CH,), 1.96 1s. 30H. C,(CH,),I. 3.97 (s, 3H. OCH,). ' H N M R (C,D,.
50OMHz.25'Cj:d =1.26(~,3H,CH~),1.72[s.30H,C,(CH,),],1.77(~,2H,CH,),
3 3 4 (s, 3H. OCH,). i3C{'H) NMR (CDCI,. 125MHz. 25'Cj: 6=12.1
[C,(CH,),I, 13.0 (CH,). 55.7 (CH2). 65.3 (OCH,). 125.7 [C,(CH,),], 145.9
[C=CCH,(OCH,)]. 169.3 [C=CCH,(OCH,)], 218.8, 230.3, 235.4 [cis-Cr(CO),].
336.7(C=Cr). MS(70eV)m/r(%):595(1)[Mi + l ] , 5 3 9 ( < l ) [ M t - 2CO +1],
4 9 6 ( < 1 ) [ M t - 3CO-CH3 +l ] . 4 5 9 ( 2 ) [ Mt -Cp*], 318(21)[Cp:Ti+].
10: Redcrystals, yield 120 mg, 34%, m.p. 186-188 "C (decomp.), correct elemental
analysis.IR(KBr).i. = 2043s.1963m,1926s.1899vs,1876s(CO),1561 m(C=C),
1236s(0CH3).lR(CH,CI,):i.=
2044s,1959sh,1915vs.1564m,1232s.iHNMR
(CDCI,. 500 MHz. 25°C): 6 = 1.92 [S. 30H. C,(CH,j,]. 2.08 (s, 2H. CH,). 2.89 (s,
3H. CH,), 3.77 ( s , 3H, OCH,). '3C{iH)NMR (CDCI,. 125 MHz, 25°C): 6 =12.0
[C,(CH,),]. 17.5 (CH,). 54.6 (OCH,), 66.0 (CH,). 125.1 [C,(CH,),]. 153.8
[C=CCH,(OCH,)]. 165.7 [C=CCH,(OCH,j], 219.1 (cis-CO), 224.1 (rruns-CO),
328.0 (C=Cr) SIMS-MS (Cst, 20 kV, 3-nitrobenzyl alcohol): positive ions m / z
( O h ) : 510 (13) [M'
- 4CO], 482 (13) [ M + - SCO], 318 [Cp:Ti+]; negative ions
m/: (%I: 622 (3) [M']. 594 (2) [ Mi - CO]. 566 (1) [ M i - 2CO], 459 (40)
[ M - co - Cp*].
13: A solution of 9 in CDCI, (2 mL) is exposed to a CO atmosphere (1 atm) for
30 min (yield 87% by 'H NMR). 1R (CH,CI,): = 2042 s. 1958 sh, 1913 vs (CO),
1563cm-I (C=C). 'H N M R (CDCI,. 500MHz. 25°C): 6=1.93 [s, 30H.
C,(CH,),I. 2.01 (s, 3H, CH,). 2.07 fs. 2H. CH,), 3.85 ( s , 3H, OCH,). "C('H)
NMR (CDCI,. 125 MHz. 25°C): 6 =11.9 [C,(CH,)J, 15.9 (CH,). 54.8 (OCH,).
65.5 (CH,). 125.0[C,(CH,)J. 146.7 [C=CCH,(OCH,)]. 161.3 [C=CCH,(OCH,)].
220.0 (as-COj, 225.8 (trans-CO). 327.8 (C=Cr).
+
I
9
10
+ CO (1 atrn)
Received: January 2. 1996
Revised version: March 25. 1996 [Z8691 IE]
German version: Angew. Chem. 1996, 108, 1636-1638
.l3
-
primary interaction of the nucleophilic and the electrophilic
carbene carbon atoms shown in 11, which is supported by coordination of CO to the oxophilic titanium center. Titanium-centerd cycloaddition of the allene molecule with the remaining
Cr(CO), fragment leads directly to 9 and, after fast CO addition
from 8, to 10. 'HNMR spectroscopy confirms that 10 is the
preferred product rather than 9 (10:9 = 4: 1).
Under a CO atmosphere the OCH, coordination to the Cr
center is reversed, and 13 is formed. In solution 10 can be converted thermally (60 "C) into 9 by elimination of one CO. This
reaction is much faster in the presence of PMe,. No products
could be isolated because of the lability of these phosphane adducts. However, the substitution of one CO ligand
by PMe, is detectable spectroscopically. The formation of
an equilibrium between 10 and 12 or the removal of the exocyclic C=C double-bond character by contribution of ionic resonance forms of the vinylcarbene moiety1161can explain the
isomerization of the double-bond system during thermolytic
formation of 9 from 10. The conversion of 13 into 10 is not
observed.
The described reaction represents, to our knowledge, the first
example of an intermolecular coupling of inversely polarized
carbene ligands. The metal-centered coupling of several carbon
atoms of different substrates" I' is thereby enlarged by an additional reaction type, which opens up a new potential for synthesis.
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Keywords: carbene complexes carbon-carbon coupling *
chromium compounds titanium compounds - vinylidene complexes
Weinheim, 1996
[I] J. M. O'Connor. L. Pu. A. L. Rheingold. J. A m . Chem. Sor. 1990, 112, 62326247.
[2] Early reports describe the liberation of olefins from monocdrbene complexes:
a) C. P. Casey, R. L. Anderson. J. Chem. Soc. Chem. Commun. 1975,895-896;
b) W. A. Herrmann. Cliem. Ber. 1975, 108,486-499; c) E. 0. Fischer, K. H.
Dotz. J. Organomel. Chem. 1972,36, C4-C6; d) E. 0. Fischer, B. Heckl, K. H.
Dotz, J. Miiller, H. Werner, ibid. 1969. 16, P29-P32; e) E 0. Fischer, A.
Maasbol, ihid. 1968. 12. P15-Pl7.
[3] Isomerization reactions 2 -1 + 2 : E. L. Weinberg, J. T. Burton, M. C. Baird.
M. Herberhold, 2. Nururforsch. B 1981, 36,485-487.
141 Dimerization of carbenes on metal surfaces: a) H. Bock
Wolf. J. Chem. Soc. Chem. Commun. 1986,1068-1069
Pet1it.J. Am. Chem. Soc. 1981.103.1287-1289; c) ibid. 1980,102,6181-6182.
[5] Reactions of the type 2 -1 are known for electron-rich alkenes. a) M. J. Doyle,
M. F. Lappert, P. L. Pye, P. Terreros. J. Chem. Sor. Dulron Truns. 1984,23552364; b) P. B. Hitchcock. M. F. Lappert. P. Terreros, K. P. Wainwright.
J Chem. Soc. Chrm. Commun. 1980, 1180- 1181; c) M. F. Lappert, P. L. Pye,
J. Chem. Soc. Dullon Trans. 1978,837-844; d) P B. Hitchcock. M. E Lappert,
P. L. Pye, h i d . 1978. 826-836; e) M. F. Lapperr, P. L. Pye, h i d . 1977, 12831291; f) M. F. Lappert, P. L. Pye, G . M. McLaughlin, ibid. 1977, 1272- 1282;
gj M F. Lappert, P. L Pye, ibid. 1977.2172-2180; h) P. B. Hitchcock, M. F.
Lappert. P. L. Pye. hid. 1977, 2160-2172; i) B. Cetinkaya, P.Dixneuf, M. F.
Lappert, ihid. 1974, 1827-1833.
[6] a) C. N . Wilker, R. Hoffmdnn. 0. Eisenstein. Neii. J. Chem. 1983. 7, 535-544;
b) R. Hoffmann. C. N. Wilker. 0 . Eisenstein, J. Am. Chem. Soc. 1982, 104.
632 -634; c) R. Schmidt. Theoretische Unrersuchungen zu Aufbau und Spullung
o1ef;nurripr Bindungen un iihergungsmeruilfragmen~en,Dissertation, Technische Universitdt Miinchen. 1988.
[7] Intermolecular C-C coupling of carbene ligands of the Schrock type during
thermolysis or decomposition reactions of homonuclear compounds are formulated via 1.3-dimetallacyclobutanes. in contrast to the transformation
0570-0833/96/3513-1566$ 15.00+.25/0
Angew. Chem. Inr. Ed. Engl. I%,
35, No. 13114
-
-
3 4 : a) D H. Berry, T. S. Koloski. P. J. Carroll, Organornetallics 1990, 9,
2952-2962; h) 1. M. Saez, N. J. Meanwell, A. Nutton. K. Isohe, A. V.
de Miguel. D. W. Bruce. S. Okeya. D. G. Andrews. P. R. Ashton, I. R. Johnstone, P M. Maitlis, J. Chem. Soc. Dalton Trans. 1986. 1565-1575; c) K. C.
Ott. R. H Grubhs, J. Am Chem. Soc. 1981,103,5922-5923;d) R. R. Schrock.
P. R. Sharp, hid. 1978.100.2389-2399.e)C. Masters, C. Vander Woude, J. A.
Van Dorn. ihiu'. 1979, 101. 1633-1634; f) J. H. Merrifield, G:Y Lin. W. A.
Kiel, J. A. Gladysz. ibid. 1983. 105, 5811-5819.
[8] a) R . Beckhaus. S. Flatau, S I. Troyanov, P. Hofmann. Chem. Ber. 1992,125,
291 299: b) R. Beckhaus, 1. StrauB. T Wagner. P. Kiprof, Angeiv. Chem. 1993.
105.281 -283: Aiigew. Chem. Int. Ed. Engl. 1993.32,264-266;~) R. Beckhaus,
J Oster. T Wagner. Chem. BLw. 1994,127,1003-1013;d) R. Beckhaus. J. Oster,
2. At7org. A l l , . Chem. 1995.621. 359-364; e) R. Beckhaus. J. Sang. T. Wagner,
B Gamer. OrpmrmetuNics 1996, 15. 1176- 1187; f ) R. Beckhaus, I. StrauB. T.
Wagner, Angmr. C'hem. 1995, 107, 738-740; Angen. Chem. I n l . Ed. Engl. 1995,
~
34. 688 690
191 a) R Beckhaua, J. Sang, J. Oster, T. Wagner, J Organomel. Chem. 1994, 484,
179-190; h) R. Beckhaus, 1. StrauB. T. Wagner, J. Organomel. Chem. 1994,
464. 155 -- 161.
[lo] Crystal structure analysis of 9 : STOE-IPDS diffractometer, graphite
monochromated Mo,, radiation, j. = 0.71069 A, structure solution direct
methods (SHELXS-86: G. M. Sheldrick, Acta Crystallogr. Serf A 1990, 46,
467). last square refinement against F2 (SHELXL-93: G. M. Sheldrick, University of Gottingen, Germany 1993. unpublished). Structure representation.
XP (Siemens). 0.3 x 0.1 x 0.05 mm, dark-red prism (very weak diffracting),
spacegroupP?(No. 2). tric1inic.u =10.170(1).6 =17.440(3).c =18.718(3)&
1 = 63.04(2). /{ = 82.34(2). ,; = 90.00(2), V = 2925(1) A3, Z = 2. pcd,cd
=
1.346 gem-'. 20421 collected, 8677 unique. 2666 observed ( I = 241).
R = 0 057. ivR2 (all data) = 0,154,686 parameters. Crystallographic data (excluding structure factors) for the structure(s) reported in this paper have been
deposited with the Cambridge Crystallographic Data Centre as supplementary
publication no CCDC-179-48. Copies of the data can be obtained free of
charge on application to The Director, CCDC, 12 Union Road. Cambridge
CB? 1EZ. UK (fax: Int. code +(1223) 336-033; e-mail: teched(0chemcrys.
cam.ac.uk)
[ l l ] a) K . H Dotz. H:G. Erhen, W. Staudacher, K. Harms, G. Miiller, J. Riede,
J. Orgunomrr.C'hem. 1988,355,177-191 ;h) K. H. Dotz, W. Sturm, M. Popall.
J. Riede. i b d 1984. 277. 267- 275.
[12] U Schubert. P. Friedrich. 0 Orama, J Organomel. Chem. 1978, 144,175- 179.
[13] a ) U. Schuhert. Coorrl. Chem. Rev. 1984, 55, 261 -286; h) K. H. Dotz. H.
Fischer. P. Hofmann, F. R. Kreissl. U. Schubert, K. Weiss. Transition Meml
Curhenr Cnmp/e.re.~,
VCH, Weinheim. 1983.
[14] a ) M. Sabat, M. F. Gross, M. G. Finn, 0rganometoNic.s 1992. I f , 745-751;
b) G Erker. A q e w . Chem 1989, 101, 411 -426: Angeiv. Chem. In/.Ed. Engl.
1989. 28. 397 412.
[15] Formation of allenes is observed in reactions of diazocompounds with vinylidene complexes (Fe[lSa]. Rh [15b]): a) C. P. Casey, G. P. Niccokai.
Orgunnmc~ia/l~c.r
1994, 13. 2527-2531; b) J. Wolf. R. Zolk. U. Schubert, H.
Werner. J. Or,qmionret. Chem. 1988, 340. 161 -178.
[I61 Described. for example, for nucleophilic vinylogous reactions: R. Aumann. H.
Heinen. C'hivi7. Ber. 1987. 120, 537-540; compare ionic resonance forms of
titanaoxycarbene complexes [14a, Sc].
[17] Examples for complex metal-centered coupling reactions of different carbon
atoms: enediolate couplings: a) R. Beckhaus. D. Wilbrandt, S Flatau, W-H.
Bohmer. J Oyqmomet. Chem. 1992.423,211-222; b) K. Tatsumi, A. Nakamura. P. Hofmann. R. Hoffmann, K. G. Moloy, T. J. Marks. J A m . Chern. Soc.
1986. 108. 4467 -4476; c ) P. Hofmann, P. Stauffert, M. Frede, K. Tatsumi.
Cheni. B w . 1989. 122, 1559-1577; d) P. Hofmann. M. Frede, P. Stauffert, W.
Laser. U. Thewalt, Angeri. Chem. 1985. 97, 693-694; Angeir. Chem. In/.Ed.
En,/. 1985, 24. 712-713; at bimetallic systems: e) D. H. Berry, J. E. Bercaw.
A . J. Jircitano. K. B. Mertes. J. Am. Chent. So<. 1982. 104. 4712-4715; Dotz
reaktion: f) K. H. Dotz, Angew. Chem. 1984. 96, 573-594: Angen.. Chem. Int.
E d D7gI. 1984, 33. 587-608.
[18] R. Aumann. E. 0. Fischer. A n p i . . Cltwt. 1967, 79, 900-901; Angeir. Cl7em
Inr. Ed. En~ql 1967, 6, 879 -880.
Epothilone A and B-Novel 16-Membered
Macrolides with Cytotoxic Activity : Isolation,
Crystal Structure, and Conformation in
Solution**
Gerhard Hofle,* Norbert Bedorf, Heinrich Steinmetz,
Dietmar Schomburg, Klaus Gerth, and
Hans Reichenbach
Myxobacteria of the genus Sorangium have proved in the last
few years to be extremely versatile producers of biologically
active secondary metabolites.['] This diversity is true both for
the basic structures, which are generally new, and for the biological effects and their underlying mechanisms. Sorangia very frequently produce antifungal compounds, which may be explained by the fact that these cellulose-degrading organisms
have to compete with fungi for the same ecological niche. Also,
the Sorangium cellulosum strain So ce90 was identified during
screening by its antifungal activity, which guided the isolation of
two new, structurally unrelated classes of compounds, the
When isolated in the
epothilones Ifz,31 and the ~pirangiens.[~]
pure form, epothilonesA and B (la and lb, respectively) showed
broad activity against eukaryotic cells; the efficiency of the
methyl derivative B was mostly a factor of 2 greater than that of
the derivative A.
R
la
R=H
lb
R=CH,
The antifungal activity of 1 against oomycetes (Plasmopara
viticola, Phytophthora injestans), in vitro and in the greenhouse,[51is noteworthy, as is its cytotoxicity against mouse fibroblasts (cell line L929, l b : IC,, 2 ngmL-'), which resuIts in
disintegration of the cell nucleus and r apoptosis (programmed
cell death) within three days.[31The epothilones also showed
noticeable activity and selectivity against breast and colon tumor cell lines in the in vitro antitumor screening program of the
National Cancer Institute (NCI) .I6, 'I In addition, epothilones
were discovered independently by Bollag et al. by a tubulin
polymerization assay.[*] This assay, and subsequent detailed
studies of their cytotoxicity and inhibition of mitosis show that
the epothilones have an almost identical activity and mode of
[*I Prof. Dr. G Hofle. Dr. N. Bedorf, Ing. I. Steinmetz
Ahteilung Naturstoffchemie
Prof. Dr. D. Schomburg
ZWE Molekulare Strukturforschung
Dr. K. Gerth, Prof. Dr. H. Reichenbach
Abteilung Naturstoffbiologie
Gesellschaft fur Biotechnologische Forschung
Mascheroder Weg 1, D-38124 Braunschweig (Germany)
Fax: lnt. code +(531)6181-461
[**I Antibiotics from Gliding Bacteria, Part 77. Part 76: D. Schummer, E. Forche.
V. Wray. T. Domke. H. Reichenbach. G. Hofle. Liebigs Ann. 1996, 971 -978.
We thank Dr. A. Ross and colleagues at the Bio Pilot Plant of the G B F for help
with fermentations, Dr. V. Wray and colleagues from Instrumental Analytics
Group for recording the NMR and mass spectra. and B. Pluta. A. Ritter, and
K. Schicht for technical assistance. This work was supported by the Fonds der
Chemischen Industrie.
Angeii. Chrm Ini. Ed. EngI. 1996, 35, N o . 13/14
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