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OMe
w as quenched w ith an excess o f m ethyl iodide w ith in 30 min at
0 °C . Subsequent cy clization to the hem iketal in acid ic m edium
gave soraphen A la ( l a ) in 70% yield.
R eceived; Ju ly 20, 1994 [Z 7149]
G erm an version: Angew, Chem . 1 9 9 4 ,106, 2521
OMe
15
OMa
16
Schem e 4. u) /B u L i, T H F , 90 m in , - 7 8 °C : B zC l, p y rid in e, 1 2 h , 2 0 “C ; 5 % N a /H g ,
5 h , - 20 "C, 3 5 % ; b) B u4N F , T H F , I h , 0 ° C , 8 5 % ; c) nB yL i, C l C 0 2E t, T H F , 1 h,
- 3 0 “C, 8 5 % ; d) m o rp h o lin e, T H F , 2 h , reflu x ; 6 0 % C H 3C 0 2H , 2 h , 50 C , 7 5 % ;
e) TBD PSC 1, im id azo le, D M F , 7 d , — 60 “C , 9 6 % ; f) A c20 , p y rid in e , 4-d im elh y lam in o p y rid in e, 30 m in, 0 'C , 9 8 % ; g) H C (O M e )a , C H ,C 1 2 , M e O H , 4 d , 2 0 ° C ,
9 9 % ; h) T i( 0 /P r ) 4 , 2 -(trim eth y lsiIy l)eth an o I, 3 d , 1 0 0 “C, 9 0 % ; i) C sF, D M F , I d ,
2 0 "C, 9 8 % ; j) thexyldim ethylsilyl c h lo rid e (T D M S C I), C H 2C12, trieth y h im in e ,
20 m in, 2 0 " C ; ( C H j) 2C = C B r ( N M e 2), C H X 1 ,, trie th y la m m e , 1 h, 2 0 “C , 91 % ; k)
triethylam ine, a c e to n e , H 20 , 15 ra in , R T ; C s 2C 0 3, D M F , 1 d , 20 “C, 5 0 % ; I) te lrab u tyliim m onium fluoride, T H F , 4 h , 0 “C , 1 M HC1, T H F , I d , 2 0 "C , 9 5 % ; m)
2 e q u iv o r p o ta ss iu m -2 ,6 -d i-rm -b u ty lp h e n o x id e , D M F , I d , 2 0 °C ; M e l, D M F ,
m olecular sieves (4 A ), 30 m in, 0 “C ; HC1, T H F , 1 2 li, 20°C , 7 0 % ,
m ate after d e sily la tio n .1131 S u b se q u e n t a d d ition o f w ater across
the triple b o n d via an e n a m in e in term ed ia te fo llo w e d by c le a v ­
age o f the p rotectin g g r o u p s resu lted in the tetrah yd rop yran
ring structure o f 15. E xp e r im e n ts by G . H o fle et al. o n the ringopened so ra p h en d em o n stra te d th at th e la cto n iz a tio n is best
effected by a su b stitu tio n rea ctio n o f the cesiu m sa lt o f the
carb oxylic a c id .'141 T h erefo re, b en zyl a lco h o l 15 and th e b r o m o
enam ine rep orted by G h o se z e t a l . I15] were a llo w ed to react
under m ild c o n d itio n s an d y ie ld e d b rom id e 16 w ith c o m p lete
inversion. T h e m a c ro c y cliza tio n o f the cesiu m ca rb o x y la te o f 16
(20 °C, 60 % yield ) p ro d u ce d th e so r a p h en ring structure also
with in version at the b en zyl g ro u p . S in ce the m eth yl g r o u p in
soraphen A Ja (1 a), that is in a -p o s itio n to the la cto n e occu p ies
the th erm od yn am ically fa v o r e d c o n fig u r a tio n ,1163 it w as in tr o ­
duced in the last step o f th e sy n th e sis. By u sin g tw o e q u iv a len ts
o f p otassiu m 2 ,6 -d iim -b u ty I p h e n o x id e , the h e m ik e ta l rin g o f
norsoraph en I b w as o p e n e d a n d d e p r o to n a te d to give the
potassium e n o la te. To a v o id o v e rm e th y la tio n , the e n o la te ion
2468
©
V C H Verlagsgeselhichafi m b H , D -69451 W einheim , 1994
[1] H . R eichenbach, G . H öfle, H . A ug u stin iak , N . B edorf, E. F o rch e, K . G erth,
H . Irschik, R. Jau sen , B. K u rze, F. Sasse, H. Steinm etz, W. Trow itzsch-K ienast,
E P 282455; [Chem. A b str. 1989, 111, 132597].
[2] N . B edorf, D . S ch o m b u rg , K . G erth , H . R eichenbach, G . Iiö fle , Liebigs Ann.
Chem . 1993, 1017.
[3] J. R ohr, N achr. Chem , Tech. L ab. 1993, 41, 889.
[4] M . B öhringer, H .-J. R o th , J. H unziger, M . G ö b el, R. K rish n a n , A . G iger, B.
Schw eizer, J. S ch reib er, C, L e u m an n , A. Eschenm oser, lie lv . C hun. A c ta 1992,
75, 1417; R. J. F e rrie r, N . P rasad , J. Chem. Sue. C. 1969, 570.
[5] E. J. C orey, D . Seebach, A n g e it'. Chem. 1965, 77, 1134; Angew . C hem . Int. Ed.
Engl. 1965, 4, 1075. T h e su b stitu tio n reaction on p h en y lo x iran c resulted in a
regioselectivity o f 8:1 ( —35 °C) in fav o r o f the desired isom er.
[6] S. H an essian , J.-R . P o u g n y , I. K . B oessenkool, Tetrahedron 1984, 40, 1289.
[7] M . T. R eetz, A ngew . Chem. 1984, 96, 542; Angew . Chem. Int. E d Engl. 1984,
23 ,5 5 6 . W h e n using the m agnesium salt o f acetylcnc on ly the d esire d i>-g/veero
isom er 11 was d etected . T h e fo rm a tio n o f the L-glycero isom er, how ever, was
favored in a ra tio o f 8:1 w hen using the triiso p ro p y lo x y titan iu m salt.
[8] F u rth e r d etails o f th e crystal stru ctu re investigation are av ailab le on request
fro m the D irecto r o f the C am b rid g e C ry stallo g rap h ic D a ta C en tre, 12 U nion
R o ad , G B -C am b rid g e C B 2 1EZ (U K ), on q u o tin g the full jo u r n a l citatio n .
[9] M . Julia, J.-M . P aris, Tetrahedron L ett. 1973, 14, 4833.
[10] G . P ro cter, D . G en in , Carbohydr. R es. 1990, 202, 81.
[11] I. N ak ag aw a, T. H a ta , Tetrahedron L e tt. 1975, 16, 1409.
[12] F o r the stereo ch em istry o f the Ju lia reactio n see P. J, K ocienski, B. L ythgoe, S.
R u sto n , J. Chem. Soc. P erkin Tram . 1 1978, 829,
[13] G . Solladie, C. H a m d o u c h i, Synthesis 1991, 979.
[14] D . S chum m er, B. B öh len d o rf, M . Kiffe, G. H ö lle in A n tib io tics and Antiviral
Com pounds (E d s.: TC. K ro h n , H . A. K rist, H . M aag ), V CH , W einheim , 1993,
p. 133.
[15] F. M u n y em an a, A .-M . F risq u e-H esb ain , A. D evos, L. G h o sez, Tetrahedron
L e tt. 1989, 39, 3077.
[16] U p o n treatm en t o f so rap h en A la ( l a ) [2] w ith base (th e rm o d y n am ic condi­
tio n s), no change o f c o n fig u ratio n occurs at the m ethylated c a rb o n a to the
lactone. T he cry stal stru ctu re o f l a shows th a t the m eth o x y g ro u p o f the
te trah y d ro p y ran rin g an d the m ethyl g ro u p a to the lacto n e a re in a stcrically
favorable p o sition relative to each oth er. In the c o rresp o n d in g epi form , how ­
ever, these m ethyl a n d m eth o x y g roups are su b ject to 1,3-diaxial interactions.
T his m ight also be the reaso n w hy a possible d im eth y latio n o f n o rso rap h en 1 b
can be avoided u n d e r a p p ro p ria te reaction conditions.
Novel Bimetallic Model System for
Cytochrome P450: Effect of Membrane
Environment on the Catalytic Oxidation**
A lbertus P. H. J. Schenning, D om inicus H. W. H ubert,
Jan H. van Esch, M artinus C. Feiters,
and Roeland J. M . N olte*
C ytochrom e P450 catalyzes a variety o f ox id a tio n reactions,
inclu ding the hyd roxylation o f alkanes and the ep o x id a tio n o f
alkenes.111 The active site o f this m em brane-bound enzym e con ­
tains a hem e fu n ction and a thiolate as axial ligand. T h e catalyt­
ic cycle involves the binding o f a substrate, reduction o f iron(m)
to iron (n), and bin ding and reductive cleavage o f m olecular
oxygen to generate w hat is form ally an o x o iro n (v ) com plex,
[*] P rof. D r. R . J. M . N o lte, D ip l.-C h em . A. P. II. J. Schenning, D . H . W. H ubert,
D r. J. H. van E sch, D r. M . C. F eiters
D ep artm en t o f O rg an ic C hem istry, N S R C en ter, U niversity o f N ijm egen
T oernooiveld, N L -6525 E D N ijm egen (The N eth erlan d s)
Telefax: In t. code + (80)55-34-50
[**] T his w ork was s u p p o rte d by the N eth erlan d s F o u n d a tio n fo r C hem ical R e­
search (SO N ) w ith financial aid from the N eth erlan d s O rg an iza tio n lo r Scien­
tific R esearch (N W O ).
0570-11X3319412323-2468$ 1 0 .0 0 + .2 5 /0
Angew. Chem. In t. Ed. Engl. 1994 ,33, No. 23124
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which transfers its oxygen atom to the bou nd substrate. The
iron cen ter accepts the electrons from N A D P H , through m edia­
tion o f a flavop rotein .
B ecause o f its b iological im portance— this enzym e plays a
crucial role in the m etab olism o f end ogen eou s chem icals and
x en ob iotic c o m p o u n d s - and also because this archetype oxida­
tion catalyst m ay serve as a m odel for a new generation o f
synthetic catalysts, a great deal o f research is currently focused
on m im ick in g the action o f cytochrom e P450.[2] U n til n o w only
a few m o d els have been described that incorporate the im por­
tant featu res o f the natural system , nam ely m olecular oxygen as
the o x id a n t, a m etalloporph yrin as catalyst, an electron don or,
and a m em b ran e system h old in g these com p on en ts.131 A ll m od ­
els have the disadvantage o f displaying very low catalytic activity.
D u rin g the course o f our studies on novel supram olecular
catalytic system s, w e fou n d that the rhodium com plex [R hnl(ij5C p *)(b p y)C l2] (Cp* = pentam ethylcyclopentad ienyl, bpy =
2,2'-bipyridine) is an efficient catalyst for the reduction o f m anganese(m ) porphyrins by sodium form ate.141 We report here on
a m em b ran e-b ou n d cytoch rom e P450 m im ic that epoxidizes
alkenes w ith g o o d turnover num bers. T h e system is com p osed
o f vesicles con tain in g an a-(aceto)-[5,10,15,20-tetrakis(2,6-dichlorop henyl)-porph yrinato]m angan ese(m ) catalyst ([M nmt2 6 diClPP] 1 ),[51 jV -m ethylim idazole as axial ligand, and an am phiphilic rhodiu m (m ) com p lex (2 ) [6! in com b in ation w ith sodi­
um form ate as electron don or. We found that the type o f m em ­
brane has a dram atic effect on the catalytic activity o f the m im ic.
T he m an gan ese porphyrin I and the rhodium com plex 2 were
incorp orated into p ositively charged dim ethyl-dioctadecylam m onium chloride (D O D A C )[?1 and negatively charged dih exad ecylp h osp h ate (D H P ) [?1 vesicles by the ethanol injection
m eth od .[lil G el perm eation chrom atograph y and electron m i­
croscop y w ere used to sh o w that the porphyrin and the rhodium
com plex were bou nd to the bilayers o f the vesicles and that the
vesicle structure w as not destroyed by the incorporation proce­
dure. T h e diam eters o f the vesicles o f b oth am phiphiles am oun t­
ed to a b o u t 4000 A. T he fluorescence spectra o f H 2-t2 6-diClPP
in b oth D O D A C and D H P vesicles ( T = 7 0 °C) show ed n o ef­
fects o f self-q u en ch in g w hen the porphyrin to lipid ratio w as
low er than 0.005. T his indicates that below these ratios the
porphyrin m olecu les are n ot aggregated.191 The addition o f w a ­
ter-soluble quenchers (N a l and C u S 0 4 in the case o f D O D A C
and D H P vesicles, respectively) to the system did not change the
fluorescence spectrum o f the vesicle-bound H 2-t2i6-diC lPP.
M ost lik ely the porphyrin is situated in the inner part o f the
vesicle bilayer. E P R studies, using [Cun(t2i6-diClPP)] instead o f
1 revealed th at for b oth vesicle system s the orientation o f the
porphyrin m olecu les w as parallel to the vesicle surface.1101 T he
structure o f the m odel system is depicted in Figure 1.
First w e investigated the influence o f the m em brane m atrix on
the red uction o f the m anganese(in) porphyrin. To this end the
Angew. C/icm . Ini. Ed. Engl. 1994 ,33, No. 23/24
©
vesicle bilayer
f V
/ W
\A
/W
N A A A /V V V V X
\^ v V \A A A /A /V V y — ^
V V W V V V X A A A A /W V V W
co m p lex 2
p o rp h y rin 1
A r w w w v
V
W
H C 02- \
W
W
V
\
/V W
V V W
/■ [Rhl"(Cp*)(bpy)]2+
C02 A'V^ [HRh1"(Cp*)(bpy)]+ /
\
W
A
o
Mn‘"(P) > ^ ) A ( + Hî°
Fig. 1. S ch em atic re p re s e n ta tio n o f th e c y to c h ro m e P4S0 m im ic an d th e catalyzed
reac tio n ,
d ecrease in the a b so rp tio n at 660 nm (M n UI porph yrin ) and the
in crease in ab so rp tio n at 448 nm (M n" p orp h yrin ) in th e U V /
V IS sp ectru m w a s fo llo w e d as a fu n ctio n o f tim e, b oth under an
argon atm osp h ere and in air. T h e rh o d iu m com p lex m a n g a n o p orp h yrin ra tio w as varied from 0.5 to 10. U n d e r argon in
D O D A C as w ell as in D H P vesicles, th e M n"1 porph yrin w as
red uced at all R h /M n ratios tested . T h e red u ction rate w as
fo u n d to increase lin early w ith th e R h 111 c o n cen tra tio n . A t a
fixed R h /M n ratio the red u ction w as faster in D O D A C vesicles
th an in D H P vesicles ([R h ]/[M n] = 1; k 0 (D O D A C ) >
100 n m o lL
s
, k a (D H P ) = 20 + 2 n m o lL ' ' 1 s ~ ‘). T h e red u ctio n o f M n 111 in D O D A C v esicles a lso to o k p lace w hen the
r eaction s w ere carried o u t in an air a tm o sp h ere. A sim ilar result
w as ob ta in ed fo r D H P ex cep t w h en the R h /M n ratio w as equal
or less than 1, under w h ich c o n d itio n s reo x id a tio n o f M n 11 w as
ob served . In th e ab sen ce o f the R h in c o m p le x or form ate no
red u ctio n to o k place. T h e se results in d ic a te th a t the rhodiu m form ate system is ca p a b le o f red u cin g the m em b ran e-b ou n d
M n 111 p orp h yrin and p resu m ab ly, as o b serv ed p r e v io u sly ,141 the
rh od iu m c o m p lex acts as a r ed ox-active p h ase transfer catalyst
in th is process. T h e red u ctio n o f M n 111 is faster in the p ositively
charged vesicles than in th e n egatively ch arged on es becau se the
fo rm a te c o n c en tra tio n is high er at the b ilayer/w ater interface o f
the form er aggregates. T h e fact th a t in D O D A C vesicles in gen ­
eral an d in D H P vesicles w ith a R h /M n ratio high er th an 1 no
r eo x id a tio n o f M n 11 takes p lace, in d ic a tes th at th e red uction o f
m a n g a n ese is m u ch faster than its reo x id a tio n .
In a seco n d series o f exp erim en ts w e in v estig a ted w h eth er our
m e m b ra n e-b o u n d cy to ch ro m e P 450 m im ic w as able to ep oxid ize
alk en es. T he results are listed in T able 1. A ll su bstrates tested
w ere ep o x id ized by th e catalytic system based o n D H P vesicles.
T h e turnover nu m b ers are high er th an th o se ob tain ed w ith the
tw o -p h a se system p r e v io u sly p u b lish ed by us.[41 T hey are in the
sa m e range as th ose ob served for the natu ral system (1 nm ol
p r o d u ct per n m o l P450 p er m in ).111 R em ark ab le is the high sta­
b ility o f the ca ta ly st d u rin g the reaction , w h ich is in contrast
w ith the tw o -p h a se system . T h e e ffect o f the m em b ran e en viron ­
m e n t on the c atalytic e p o x id a tio n b e c a m e clear w hen the D H P
vesicles w ere replaced by the D O D A C vesicles. In the latter
m em b ran e sy stem no e p o x id a tio n o f alk en es w a s observed (last
tw o entries o f T able 1 ). P resu m ab ly, th e c o n c en tra tio n o f p ro­
to n s is to o lo w to allo w th e form ation o f the cata ly tica lly active
o x o m a n g a n e s e (v )u l) sp ecies at the p o s itiv e ly charged interface.
W h en th e R h /M n ratio w as increased fro m 1 to 10 the turnover
num ber o f the reaction decreased considerably (Table 1, entry 5).
T h is p h en o m en o n is p o ssib ly caused b y the fact that m ore elec-
VC H Vertagsge.iellschafl m b ll, D -69451 W cm heim , 1994
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2469
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Table 3. E poxidation o f alkenes by the m em brane-bound cy to ch ro m e P450 m im ic
[a]E ntry
S urfactant
S ubstrate
P roduct [b]
T u rn o v e r
n u m b e r [c]
1
2
3
4
5
6
7
DHP
DHP
DHP
DHP
D H P [e]
DOD A C
D O D A C [e]
a-pinene
iy.y-stilbene
lim onene
styrene
styrene
styrene
styrene
a-pinene oxide
«■«-stilbene oxide
lim onene oxide
styrene oxide [d]
styrene oxide
-
360
45
50
55
5
0
0
1,4-Didehydrobutadiene: The Intermediate in a
New Class of Thermally Induced Intramolecular
Alkyne Couplings**
R olf G leiter* and Joachim R itter
-
D e d ic a te d to P ro fe sso r H ein z D im
on the occasion o f his 60th birthday
[a] F o r reaction conditions see E xperim ental P rocedure. T he reaction w as follo w ed
by G L C for 1 h. N o destruction o f the catalyst was found after th a t p erio d , [b] T he
only p ro d u c t o f the reaction was epoxide, which was gradually d ec o m p o sed in to
o th e r products. The decom position processes were independent o f th e R h /M n ratio .
N o epoxide was form ed w ithout vesicles o r when any o f the c o m p o n e n ts o f the
catalytic system were om itted, [c] T urnover n um ber [epoxide]/l p e r h o u r, ca lcu la ted
from the initial p a rt o f the convcrsion/tim e plot. a-Pinene oxide w as co n v e rted
( > 9 0 % ) in to pinocam phone w ithin a period o f one hour. L im onene o x id e d e c o m ­
posed ( ± 5 0 % ) into as yet unidentified products, [d] Styrene o xide a n d stilb en e
oxide w ere stable under the experim ental conditions, [e] R h /M n m o la r ra tio = 1 0 .
Irons becom e available due to the higher concentration o f rh od i­
um centers. As a result a side reaction can take place w hich
produces water (the so-called non-productive p ath w ayt u I ).
In summary, we have developed a bimetallic m em brane-bound
cytochrom e P450 mimic which catalyzes the epoxidation o f alke­
nes with good turnover numbers. Current work is aim ed at devel­
oping catalytic systems that display substrate selectivity.
M ore than tw en ty years ago Bergman and co-w ork ers d isco v ­
ered that enediynes su ch as (Z )-hexadiyn-3-ene (1) cyclize to
give the corresp on d in g 1,4-didehydrobenzenes (2) as short-lived
interm ediates.111 This reaction occurs at 200 °C w ith an activa­
tion energy o f 28 k c a lm o l-1 (Schem e l ) . 12"1 The recent discov-
Schem e 1. C y clo aro m atiza tio n o f enediynes.
Experim ental Procedure
R eduction experim ents: T he desired am o u n ts o f stock solutions o f 1, 2, Nm ethylim idazole, and D H P o r D O D A C in chloroform were m ixed in a test tu b e .
T h e solvent was evaporated u n d er a strea m of nitrogen to leave a h o m o g e n e o u s
film. T his film was solubilized in 100jj.L e th an o l/tetra h y d ro fu ran (1 :1 , v/v ) an d
injected in 1 .2 5 m L w ater a t 75°C . T h e suspension was purged w ith a rg o n for
30 m in and injected in a cuvette containing 1.25 m L o f an e th y lm o rp h o lin e/so d iu rn
fo rm ate buffer at 75 X . Final conditions; 2.4 |iM o f 1, 2.4 x n jjm o f 2 (// = R h /M n
m olar ra tio ), 3.95 j.im o f /V-methylimidazole, 910 hm D O D A C or D H P in eth y lm o rpholine (50 mM)/sodium form ate (250 mM) buffer (pH = 7 .0 ), T = 7 0 °C .
E p oxidation experim ents: F inal conditions as above, except R h /M n m o la r ra tio = 1
and [substrate] = 200 j-tM. N ow the 100 |.iL solution was directly injected in a 2.5 m L
buffered solution at 75 °C. S ubstrate w as added and the reaction m ix tu re w as a n a ­
lyzed from tim e to time by taking a 0.2 m L aliquot to which w as a d d e d O.J mL
diethyl eth er containing mesitylenc as an internal standard. This m ix tu re w as sh ak en
vigorously (vortex ap p a ra tu s) and centrifuged. A fter phase s e p a ra tio n , a 5 j.iL
sam ple was taken from the diethyl eth er layer and analyzed by G L C (co lu m n
C h ro m p ack , W C O T/C P-SIL5C B , tem perature p rogram 7 0 "C (2 m in ), 10 K m in “ 1
200 “C (2 m in)).
Received: M ay 2, 1994 [Z 6891 IE]
G erm an version: Angew. Clwm . 1994, 106, 2587
[1] F. P. G uengerich, J. Biol. Clwm. 1991, 266, 10019.
[2] J. P. C ollm an, X . Z hang, V, J. Lee, E, S. U ffelm an, J. I. B raum an, S cien ce 1993,
261, 1404.
[3] a) J, H . van Esch, M. F. Roks, R. J. M . N olte,
A m . Chcm . Soc. 1986, 108,
6093; b) J. T. G roves, R . N eum ann, ibid. 1989, I I I , 2900; c) J. T. G ro v e s , S. B.
U ngashe, ibid. 1990, 112, 7796.
[4] P. A . G osling, J. H. van Esch, M. A . M , H offm ann, R. J. M . N o lte , J. C hem .
Soc. Chem. Conmmn. 1993, 472.
[5] A . D . A dler, F. L. L ongo, F. K am pas, J. K im ,./ Inorg. Nucl. C hem . 1970, 32,
2443.
[6] a) U , K ölle, M , G rätzel, Angew, C hem . 1987, 99, 572; stjigeii'. C hem . In t. Ed.
Engl. 1987, 26, 567; b) J. H . van Esch, M . C. Feiters, R . J. M . N o lte , J. O rg .
Chem., in press.
[7] A . M . C arm ona-R ibeiro, Chem. Soc. Rev. 1992, 209.
[8] L. A. M , R upert, D . H oekstra, J. B. F. N . Engberts, J. A m . Chem . Soc. 1985,
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2470
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VCH VerlagsgeseUschaft m b ll. D-69451 W em heim , 1994
ery o f the natural an titu m or antibiotics calicheam icin, esperam icin, and dyn em icin , w hich contain the cyclic en ed iyn e unit 3,
led to an en orm ou s increase in publications on en ediyne ch em ­
istry in the last seven years.131 A com m on feature in the m ech a­
nism o f action o f these antibiotics is the cy cloarom atization o f
the enediyne unit 3 to give the bicyclic 1,4-didehydrobenzene 4.
In the case o f n eocarzin ostatin, the electrocyclization o f an
initially generated cyclic (Z )-cum ulene-enyne 7 is p ro p o sed as
the key step .141 In related work M yers et al. found that the sur­
prisingly facile cyclization o f the open-chain cum ulene 5 gives
a,3-d eh yd rotolu en e 6 and is an exam ple o f a new type o f a
1,4-biradical generating reaction (Schem e 2 ).[5il1
C* ^ ex.—a
< 2-
100°C
2 [HI
Schem e 2. C y clo aro m atiza tio n o f cum ulene-enynes.
[*] P rof. D r. R . G leiter, D ip l.-C h em . J. R itter
O rganisch-chem isches In stitu t d er U niversität
Im N eu en h eim er F eld 270, D -69120 H eidelberg (F R G )
T elefax; In t. co d e + (6221)56-4205
[**] T his w ork was su p p o rte d by the D eutsche F orsch u n g sg em ein sch aft, the Fonds
der Chem ischen In d u strie , an d the BA SF A ktiengesellschaft (L udw igshafen).
J. R . th a n k s the S tu d ie n stiftu n g des deutschen Volkes fo r a d o cto ral fellowship.
0570-083319412323-2470 S 10.00 + .25/0
Angew. Chem. Ini. Ed. Engl. 1994, 33. No. 23/24