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Nickel-Catalyzed Cyclodimerization of Hexapentaenes [4]Radialenes and [5]Radialenones with Cumulated Double Bonds.

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clopentadiene and 12a and 12c re~pectively."~~
We assign to
the remaining products (22 and 11 %) the structures of the
still missing cis-diastereomers 13c, d. No significant cis-trans
isomerization 12c -+ 12a ( < S o / , ) takes place under the
reaction conditions." It is demonstrated therefore, that
the cycloaddition of bicyclo[2.1 .O]pentene 6 proceeds nonstereospecifically, as expected in the case of a two-step process.
R'
12a,c
13a-d
R'
14a,c,d
,
b: R1=R4=C0,CH,, R Z = R 3 = C N ;
a: R ~ = R ' + = C NRZ=R3=C0,CH,;
c: R' = R3 =CO,CH,, R2 = R4 =CN; d: R1= R3 = CN, R2 =R4 =C02 C H 3
Finally, there remains the question of which factors are
responsible for the different course of the homo-Diels-Alder
reaction of homofuran 4 and bicyclopentene 6 . The two systems have very different strain energies. In the homofuran 4,
the strain energy is essentially determined by the cyclopropane ring, whereas in the bicyclopentene 6 it is composed
of the three- and four-membered ring strain as well as the
negative resonance energy, which is attributed to the antiaromatic character of 6 as homocyclobutadiene.r'61 In the
transition state of the two-step process, the central cyclopropane bond could be opened further than in the concerted
homo-Diels-Alder reaction. The reaction of 6 profits in particular from this bond opening, since the total strain of the
bicyclopentene is released in one step.
Received: April 4, 1990 [Z 3894 IE]
German version: Angew Chem. 102 (1990) 1097
CAS-Registry numbers6, 5164-35-2; 6a, 71215-51-5; 6b, 71276-51-2;7a, 128575-90-6; 7b, 128657.249; IZa, 35234-87-8; 12c, 101342-44-3; 13a, 128575-91-7; 13b. 128657-25-0;
13c. 128657-26-1; 13d, 128657-27-2; 14a, 128575-92-8; 14c. 128657-28-3; 14d,
128657-29-4; 1,3 . cyclopentadiene, 542-92-7.
2,3-(CO,CH,),), 6.33 (m, 2 H ; 5,6-H2); of 14d: 6 = 1.81, 2.40 (2m. 2 H ;
7,7-H2).3.72(m,2H; 1,4-H,),3.85(s.6H;2,3-(CO,CH3),),6.67(m,2H;
5,6-H2).
1111 The average CH, ...H distances were taken from MMX force field calculations: J. J. Gajewski, K. E. Gilbert, Serena Software 1988.
[12] Owing tothehigh polarityoftheolefins lOand 12a,c thereactlveintermediates of type 11 could also have dipolar structures.
[13] C. 1. Ireland, K. Jones, J. S. Pizey, S . Johnson, Synrh. Commun. 6 (1976)
185: T. Gotoh. A. B. Padias, H. K . Hall, Jr., J. Am. Chem. Soc. 108 (1986)
4920.
I141 Since the Diels-Alder reaction of 1,3-cyclopentadiene with 12c ( O T , 3 h,
THF) yields only the cis-adducts 14c and 14d in the ratio 87:13, the
rruns-adduct 14a must be formed directly from 6 in the reaction of 6 with
12c. This result indicates that the [,2 +.2]-cycloaddition also proceeds
non-stereospecifically and thus, as expected, in two steps.
[lS] After 2 h the ratio of unchanged 12c to 12a is 90:10 and after 3 h 77:23.
In a control experiment the extent of cis-trans isomerization 12c -+ 12a
without addition of 6 was determined as 28% after 3 h at O'C. It can
therefore be ruled out that 6 catalyzes the cis-trans isomerization
I 2 c - 12a. From the time-dependence of seven measurements (between 15 and 180 min) the product ratio of the reaction o f 6 with 12c was
=
extrapolated to the time t = 0. [13a:13b:13~:13d:14a:14~:14d],-,
29- 18:24: 12: 3.1 1 :4.
[16] W. R. Roth. F.-G. Klirner, H.-W. Lennartz. Chem. Ber. 113 (1980) 1818.
Nickel-Catalyzed Cyclodimerization of
Hexapentaenes: [4]Radialenes and [S]Radialenones
with Cumulated Double Bonds **
By Masahiko Iyoda,* Yoshiyuki Kuwatani, Masaji Oda,
Yasushi Kai,* Nobuko Kaneshisa, and Mobutami Kasai *
Although cumulenic double bonds"] have a wide variety
of potential reactive sites, which can lead to novel cychc
dimers, trimers, and oligomers, great difficulty in controlling
the reactivity has prevented the utilization of cumulenes in
organic synthesis. We recently reported the nickel-catalyzed
cyclooligomerization of [3]cumulenes (butatrienes) IZ1 and
the cyclodimerization of [5]cumulenes (hexapentaenes) 13] to
give various types of radialenes, and demonstrated the synthetic utility of this type of reaction. We report here
the nickel-mediated synthesis of novel [4]radialenes and
[S]radialen~nes[~]
based on the same synthetic strategy.
Tetramethyl- and tetra-tert-butyl[5]cumulenes dimerize
thermally to give octamethylcyclododeca-1,3,7,9-tetrayne
and tetrakis(di-ter~-butylvinylidene)cyclobutane.~71However, nickel-catalyzed cyclodimerization of tetraarylhexapentaene yields 1,2-bis(diarylmethylene)-3,4-bis(diarylpropadieny1idene)cyclobutane as the head-to-head dimer.13]
Thus, the known thermal and nickel-catalyzed dimerizations
of [5]cumulenes occur regioselectively. In order to investigate
the difference in the reactivity of these double bonds, we
carried out reactions of the [S]cumulenes 5 with nickel catalysts.
The [S]cumulenes 5 a-c were prepared according to the
procedure outlined in Scheme 1. Ethynylation of the ketones
W. R. Roth, M. Martin, Tetrahedron Lett. 1967, 4695.
F. S. Collins, J. K. George, C. Trindle, J. Am. Chem. Soc. 94 (1972) 3732.
Review: P. G. Gassman. Acc. Chem. Res. 4 (1971) 128.
W. R. Roth, F:G. Klarner, W. Grimme, H. G. Koser, R. Busch, B.
Muskulus, R. Breuckmann, B. P. Schoiz, H.-W. Lennartz, Chem Ber. 116
(1983) 2717.
[ S ] M. H. Chang, D. A. Dougherty, J. Am. Chem. Soc. 104 (1982) 1131.
[6] E-G. Klarner, D. Schroer, Chem. Ber. 122 (1989) 179.
[7] J. E. Baldwin, R. K. Pinschmidt, Jr., Tetrahedron Left. 1971, 935.
[S] W. Adam, A. Beinhauer, 0 . De Lucchi, R. J. Rosenthal, Tetrahedron Lett.
24 (1983) 5727.
[9] E-G. Klarner, F. Adamsky, Chem. Ber. 116 (1983) 299.
[lo] 'HNMR(400MHz,CDC13)of7a:6 = 1.77(s,3H;4-CH3),3.75(s,3H;
OCH3),4.15(dt, lH;l~H.5(1,5)=6.0,3(1,2)=J(1,3) =2.0Hz),4.30(d,
1 H ; 5-H), 6.12 (dd, 1 H ; 2-H, J(2,3) = 5.5 Hz), 6 29 (ddd, 1 H; 3-H,
43.5) i1 Hz);of 7 b : 6 = 1.40 (s, 3 H ; 4-CH3), 3.81 (dt, 1 H ; 5-H,
5(1,5)=6.5,J(2,5)=J(3,5)=0.5Hz),3.85(s,3H;OCH3),4.15(dt,
IH;
['I
I-H, J(1,2) = J(1,3) = 2.0 Hz), 5.98 (ddd, 1 H ; 2-H, J(2,3) = 6.0 Hz), 6.58
(ddd, 1 H ; 3-H). 'H NMR (400 MHz, [DJacetone) of 13a: d = 2.78 (m,
2 H ; 4,4-H,), 3.90. 3.94 (2s. 6 H ; 6,7-(CO,CH,),), 3.96 (m, 2 H ; l,5-H2),
5.89, 6.14 (21% 2 H ; 2,3-H2); of 13b: 6 = 2.78 (m, 2H: 4,4-H,), 3.78 (td,
1 H; 5-H, J(1,5)= 4 4 , s ) = 7.6, J ( 4 , S ) = 2.6 Hz). 3.89, 3.97 (2s. 6 H ; 6,7(CO,CH,),), 4.21 (m, 1 H ; I-H), 5.79, 6.11 (2m 2 H ; 2,3-H2); in the 'HNMR spectrum ofthe mixture in the reaction of 6 with 12c. the new signals
at 6 = 6.25, 5.91 and 6.05, 6.03 can be assigned to the olefinic hydrogens
[**I
2,3-H; of 14a: 6 = 1.92,2.20 (2m, 2 H , 7,7-H,, J = 10.0 Hz), 3.70 (m, 2 H ,
1,4-H2), 3.88,3.96(2~,6 H ; 2.3-(C0,CH3),). 6.45.6.61 (2dd. 2 H : 5,6-H2);
of14c:6 = 1.91,2.01(2m,2H;7,7-H,).3.75(m,2H;1,4-H,),3.77(~,6H.
[l]
[2]
[3]
[4]
1062
@> VCH VerlagsgeselkchofimhH, D-6940 Weinheim. 1990
Prof. Dr. M. Iyoda, Y Kuwatani, Prof. Dr. M. Oda
Department of Chemistry, Faculty of Science
Osaka University
Toyonaka, Osaka 560 (Japan)
Prof. Dr. Y Kai, Prof. Dr. N. Kasai, N Kanehisa
Department of Applied Chemistry, Faculty of Engineering
Osaka University
Yamadaoka, Suita, Osaka 565 (Japan)
This work was supported by CIBA-GEIGY Foundation (Japan) for the
Promotion of Science and by the Ministry of Education, Science and
Culture, Japan. (Grant-in-Aid for Scientific Research No. 63540396).
0570-OX33190jO909-1062S 3 50+ 2.510
Angew. Chem. Int. Ed. Eng/ 29 (1990) N o . 9
1 a and 1 b with lithium acetylide in T H F gave 2 a and 2b in
91 and 89% yields, respectively. The oxidative coupling of
2 a and 2b with Cu(OAc),-H,O in pyridine-methanol at
55°C afforded the diols 3 a (90%) and 3 b respectivelyr8].
Treatment of 3 a with conc. hydrobromic acid in acetic acid
furnished the corresponding dibromide 4 a (90 YO).Reduction of 4 a with zinc in T H F gave the desired [5]cumulene
5 a (95%). The conversion of 3b into 5b was carried out
by a previously reported method.[*] The cumulene 5 c was
prepared according to the procedure shown in Scheme 1
Id) 88.5/o' ; b) 89 Yo ; d) 84%; e) 81
1
7
5b
8
9
5c
10
11
3
2
5
5a
4
Scheme 2. 6 = [Ni(CO),(PPh,)J
Scheme 1. a) LiC = CH, THF, - 78 "C -t RT. b) Cu(OAc), . H,O, pyridinemethanol ( I :1). 55 ~ ' Cc. ) HBr, AcOH, RT. d) PBr,, benzene, 50 "C. e) Zn, THF,
sonication.
Although 5 a-c are less reactive than tetraarylhexapentaenes, which react smoothly with ~i(CO),(PPh,),] 6 in refluxing benzene to afford the dimers, their reactions with
stoichiometric amounts of 6 in benzene at the same temperature lead very slowly to the cyclic dimers. Thus, treatment
of 5 a with 0.5 equivalents of 6 in refluxing benzene under
argon for 24 h gave the head-to-tail dimer 7 in 82% yield.
Interestingly, the reaction of the more bulky-substituted 5 b
with 1 equivalent of 6 in refluxing benzene for 2 days resulted
in the formation of the [5]radialenone 8 in 32 YOyield, together with the corresponding [4]radialene 9 in 36% yield. The
difference in the reactivity of 5 a and 5 b towards the nickel(o)
complex may be due to steric factors. Furthermore, treatment of the most bulkily-substituted 5 c with 1 equivalent of
6 in the presence of 3 equivalents of triphenylphosphane in
refluxing benzene for 8 days gave the [5]radialenone 10 as the
main product (74%), together with a small amount of 11
(6%). Since the starting [5]cumulenes5 described here can be
prepared easily by the route shown in Scheme 1, the
[4]radialenes 7 and 9 and the [5]radialenones 8 and 10 can be
synthesized in only a few steps.
The [4]radialenes and [5]radialenones reported here are
very stable towards light and air. Molecular models show
that 7 can have a planar structure with D,, symmetry. The
'H- and I3C-NMR spectra (Table 1) reflect its highly symmetrical structure. The electronic spectra of 7 show absorptions up to 450 nm, indicating elongation of K-conjugation,
whereas the electronic spectrum of 9 shows absorption only
up to 350 nm, corresponding to its spiro-oriented allenic K
bonds. The 'H- and 13C-NMR spectra of the [5]radialenones
8 and 10 show symmetrical structures. The IR spectra contain two characteristic bands for @,y-unsaturated ketones
A n p u . Chem. Inr. Ed. Engl. 29 11990) No. 9
at 1940-1910cm-' ( C = C = C ) and 1690cm-' (C=O).
The adsorption of the ketones 8 and 10 on silica gel results
in a bright yellow coloration, and the electronic spectra of 8
and 10 in CF,COOH show a marked bathochromic shift
tailing up to 700 nm with a deep violet coloration.
Table 1. Selected physical data of compounds 7-10
7: Yellow needles (from CH,CI,-hexane), m.p. = 281 -282 "C; MS (70 eV): m/z
592 ( M e ) ; 'H NMR (400 MHz, CDCI,, 3 0 ° C TMS): 6 = 1.23 ( s , 24H; CH,).
1.45 (s, 24H; CH,), 1.65 (s, 8 H ; CH,), 1.68 (s, 8 H ; CH,); ')C NMR
(100 MHz, CDCI,, 30°C. TMS): 6 = 27.8(q), 30.3(q), 40.6(s), 41.6(s), 46.1(t),
48.0(t), 118.X~).136.7(s), 145.2(s), 148.9(s), 155.2(s), 155.9(s); UVjVIS (cyclohexane): L,,, [nm] (log B ) = 253 (4.46). 260 sh (4.42), 285 (4.22), 323 sh (4.73).
334 (4.98), 406 (3.93), 431 sh (3.82); Raman (KBr): D [cm-'1 =2005
( C = C = C = C ) , 1637, 1610 (C=C).
8 : Yellow needles (from EtOH), m.p. = 226-227°C; MS: m / t 676 ( M e ) ;'H
NMR (400 MHz, CDCI,): 6 = 1.12 (s, 12H; CH,), 1.14 (s, 12H; CH,), 1.17 (s.
12H; CH,). 1. I 9 (s, 12 H ; CH,), 1.34- 1.47 (m,16H; CH,), I .58- 1.69 (m. 8 H:
CH,); I3C NMR (100 MHz, CDCI,): 6 = 19.0(t), 19.3(t), 30.8(q). 30.9(q),
31.4(q), 31.5(q), 35.7(t). 35.9(t), 40.8(s), 41.7(s), 101.4(s), 107.7(s). 126.9(s),
128.1(s),191.9(s. CO), 196.7(s), 202.4(s);UV/VIS (cyclohexane): %,sx[nm](log
E ) = 215 (4.78). 246 (4.70). 263 sh (4.22), 298 (3.64). 313 (3.47), 378 (3.39).
408sh (3.26); IR (KBr): C[cm-'] = 1941, 3919 (C=C=C), 1691 (CEO).
9: Colorless needles (from Et,O-EtOH), m.p. = 315°C (sublimed); MS: mj;
648(Me);'HNMR(90MHz,CDCI,):6
= 1.I2(s,48H;CH3).1.25- 1.80(m.
24H; CH,); "C NMR (22.5 MHz, CDCI,): 6 = 19.2(t), 31.7(q), 35.5(t),
[nm] (log
40.9(s), 109.4(s), 127.6(~).192.5(s); UVjVIS (cyclohexane): i.,,,
E) = 215(5.13),252sh(4.27),259(4.28),268 sh(4.19).300(3.38),318(3 42),IR
(KBr): B[cm-'] = 1957, 1917 (C=C=C).
10: Yellow prisms (from Et,O-MeOH), m.p. = 220°C (sublimed); MS: mi; 628
(Me); 'H NMR (400MHz. CDCI,): 6 = 1.24 (s. 36H, r-Bu), 1.25 (s, 36H;
t-Bu); "C NMR (100 MHz, CDCI,): 6: 32.2(q), 32.5(q), 36.6(s), 36 7(s).
100.7(~),107.0(~),129.0(~).130.6(~),192.2 (s, CO). 199.2(s), 205.1(s); UV/VIS
(THF): A,, [nm] (log&)= 244(4.67), 270 sh (4.15), 300 sh (3.75). 315 sh (3.36).
378 (3.36). 408 (3.27); IR (KBr): ?[cm-'I = 1908 ( C = C = C ) , 1691 (C=O).
In order to elucidate the unique molecular structure of
[5]radialenone 10, its crystal structure was determined by
X-ray diffraction analysis."'' The crystal lattice contains
two crystallographically independent molecules, which are
found to have essentially the same structure, including the
VCH VerlugsgerelDrhuft mbH, 0-6940 Wernheim, 1990
0570-0833j90j0909-1o63 $3.50+.25/0
1063
Fig. 1. Molecular structure of 10 in the crystal (ORTEP) with the thermal
ellipsoids at the 10% probability level for the non-hydrogen atoms. The estimated standard deviations are 0.009-0.01 1 A and 0.7-0.8" for bond distances
and angles: C1-C2 1 492,C2-C3 1.483, C3-C4 1.490, C4-C5 1.488, C5-Cl 1.476,
cs-o 1.206, c i - c i o 1.322, c i o - c i i 1.302, ~ 2 . ~ 21.318,
0
~ 2 0 . ~ 2 1.312.
1
C3-C30 1.320, C30-C31 1.310, C4-C40 1.325, C40-C41 1.286; Cl-C2-C3 107 8,
C ~ - C ~ - C107.7,
I
c 5 - c i - c 2 108.4, ~ 1 . ~ 2 c2-c3-c4 107.8, ~ 3 . c 4 - c108.1,
~
c20 123.9, c ~ o - c ~ - c128.4,
~ c ~ - c ~ - c ~126.4,
o
c ~ o - c ~ - c1 ~x 7 , C ~ O - C ~ - C S
122.0, C4-CS-0 126.2, C2-Cl-CIO 129.2, C3-C4-C40 129.9, 0-C5-C1 126.0,
CS-Cl-ClO 122.4, C1-CIO-C11 175.4, C2-C2O-C21 177.7. C3-C3O-C31 179.2,
c4-c4o-c41 175.4.
conformations of the tert-butyl groups. Figure 1 shows the
molecular structure of 10 in the crystal; particularly noteworthy is the high coplanarity of the cyclopentanone ring,
the maximum atomic deviation from the least-squares plane
of the central five-membered ring being 0.03 A. The planar
structure extends to the exocyclic allenic bonds with a maximum deviation of 0.24 A. The bond distances in the carbonyl
and allene moieties of the molecule are normal, while the
bond angles C(2)-C(I)-C(lO) [129.2(6)"] and C(3)-C(4)C(40) [I 29.9(7)"] are significantly larger than the expected
value of 126" in spite of the large distance between the methyl
groups of the neighboring tert-butyl substituents. A similar
angular deformation was found in tetrakis( 1,3-dithiaindanylidene)cyclopentanone[' due to significant non-bonded repulsion between the substituents of exocyclic bonds. In
comparison with the half-chair conformation of the molecule, the planar structure of 10 may be due to the absence of
steric strain between the tert-butyl substituents as a result of
the extension of the exocyclic bonds by a cumulenic structure.
Nickel-catalyzed reactions provide the possibility of preparing highly unsaturated compounds containing functional
groups." *I The results reported here demonstrate the utility
of nickel-catalyzed cyclooligomerization for the synthesis of
highly unsaturated unique molecules.
Received: March 21, 1990 [Z 3864 IE]
German version: Angew. Chem. 102 (1990) 1077
CAS Registry numbers'
l a , 4541-35-9; 1b, 1195-93-3; l c , 815-24-7; Za, 128923-68-2;2b, 104850-88-3;
2c. 33420-19-8;3a, 128923-69-3;3b, 128923-70-6;3c, 54622-15-0;4a, 12892371-7; 4b, 128923-72-8;4c, 54622-16-1; Sa, 128949-77-9; 5b, 60004-33-3; 5c,
7171-72-4; 6 , 13007-90-4; 7, 128923-73-9;8. 128923-74-0;9, 128923-75-1; 10,
128923-76-2; 11, 7200-90-0.
[l] Synthesis and properties of cumulenes, see, H. Fischer in S. Patai (Ed.):
The Chemrstry ofAlkene.7, Wiley-Interscience, New York 1964, p. 1025 8;
H. Hopf in S . Patai (Ed.): The Chemistry of Kerenes, Allenes, and Relared
Compounds, Wiley-Interscience, New York 1980, p. 779ff.
Chem. Commun.
[2] M. Iyoda, S. Tanaka, M. Nose, M. Oda, J Chem. SOC.
1983, 1058; M. Iyoda, S. Tanaka, H. Otani, M. Nose, M. Oda, J. Am.
Chem. SOC. 110 (1988) 8494.
1064
6
VCH Verla~.~~esellschaft
mhH, 0-6940 Weinheim, 1990
[3] M. Iyoda, Y. Kuwatani, M. Oda, J. Am. Chem. SOC.111 (1989) 3761.
[4] (n-1)Methyiene n-membered ketones are an interesting class of compounds, for which we propose the generic name [nlradialenone. For example, tetraisopropyridenecyclopentanonereported by Srehling and Wilke [5]
is octamethyl[S]radialenone.
[S] L. Stehling, G. Wilke, Angew. Chem. 97(1985) 505; Angew. Chem. Int. Ed.
Engl. 24 (1985) 496.
161 L.T. Scott, G. J. DeCicco, TetrahedronLetr. 1976,2663; C. Santiago, K. N.
Houk, G. J. DeCicco, L. T. Scott, J Am. Chem. SOC.
100 (1978) 692.
171 H. D. Hartzler, J Am. Chem. SOC.88 (1966) 3155; 93 (1971) 4527.
[8] F. Bohlmann, K. Kieslich, Chem. Ber. 87(1954) 1363.
[9] T. Negi. T. Kaneda, H. Mizuno. T. Toyoda, Y. Sakata, S. Misumi, Bull.
Chem. SOC.Jpn. 47 (1974) 2398.
1101 Crystal data of 10: C,,H,,O, m = 629.1, monoclinic, space group P2,/n,
a = 16.400(2), h = 21.176(1), c = 28.087(3) A, p = 116.07(1)", Y =
A', Z = 8. D, = 0.953 gcm-'. The transformation 100/OTO/
_8762.0(16)
_
101 gives a reduced cell of P2,lc. X-Ray intensity data were measured on
a Rigaku four-circle diffractometer with nickel-filtered Cu,, radiation using a 0.3 x 0.3 x 0.3-mm crystal. A collodion coating was necessary to
prevent decomposition of the crystal. 11 023 reflections were collected up
to 28 = 120". of which 7355 had /F,l > 3u(F0)and were used in the refinement. The intensity data were corrected for Lorentz and polarization effects but not for absorption ~ ( C U , , )= 3.8 cm-'I. The crystal structure
was solved by direct method (SHELXS-86) and refined by full-matrix
least-squares (XRAY-76).Anisotropic refinement revealed the abnormally
large thermal vibration of the lert-butyl substituents, all the hydrogen
atoms connecting to those methyl carbons were difficult to locate in the
difference Fourier maps. The weighting scheme used was IV = [d(F,) +
0.003(F,)z]-'. The final R and R,indices were0.118 and 0.161, respectively. Further details of the crystal structure investigation are available o n
request from the Director of the Cambridge Crystallographic Data Centre.
University Chemical Laboratory, Lensfield Road, GB-Cambridge
CB21EW (UK), on quoting the full journal citation.
T. Sugimoto. Y. Misaki, Y. Arai, Y. Yamamoto, Z. Yoshida, Y. Kai, N.
Kasai, J Am. Chem. SOC./10 (1988) 628.
G. Wilke, Angels. Chem. I00 (3988) 189; Angew. Chem. In!. Ed. Engl. 27
(1988) 185.
Golfomycin A, a Novel Designed Molecule with
DNA-Cleaving Properties and Antitumor Activity **
By K . C. Nicolaou,* Golf0 Skokotas, S . Furuya,
H . Suemune, and D. Colette Nicolaou
Due to their fascinating structures and biological activities, natural products have been capturing the interest and
imagination of isolation, synthetic, and medicinal chemists
for a very long time.['] Designed molecules with predefined
chemical and biological properties could enrich and compliment this arsenal of substances and sharpen the capability of
chemistry to deliver biologically and therapeutically useful
compounds. Described herein are the design, synthesis, and
chemical and biological activities of a novel agent with
DNA-cleavingt31 and antitumor properties, golfomycin
A(l).[']
Detailed in Scheme 1 is the mechanistic rationale that led
to the design of compound 1 as a potential DNA-cleaving
[*I K. C. Nicolaou, Golfo Skokotas, S. Furuya, ['I
H. Suemune, D. Colette Nicolaou,
Department of Chemistry
Research Institute of Scripps Clinic
10666 N. Torrey Pines Road, La Jolla, CA 92037 (USA)
and
Department of Chemistry
University of California
San Diego, La Jolla, CA 92093 (USA)
['I Visiting scientist from Fakeda Chemical Industries, Ltd. Japan, 1989-90.
[*'I We wish to thank Drs Dee H. Huang of the Research Institute of Scripps
Clinic and Raj Chadha of the University of California, San Diego for their
help with the NMR and X-ray crystallographic investigations, respectively. We also wish to thank Professor B. Snider of Brandeis University for
valuable discussions regarding the chemistry of conjugated allenes.
0570-0833/90/0909-10643 3.50+ .25/0
Angew Chem. Inr. Ed. Engl. 29 (1990) No. 9
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