Tetrahedron Letters No.27, Printed in Great Britain,
pp. 3139-3146,
1966.
l’erw”on
Press Ltd.
TRR CIWULAR DICRROI= OF GLIbJ A. F. Beeoha
and
Ar RcL. Yathieson
Mvizion of Chezieal Physics, Chemical Research Laboratories, Australia. C.S.I.R.O., Box 160 P.O., Clayton, Victoria, (Received On the basis of reference
oozpounds,
Yozoozltz,
a rule relating
azsocleted
dth
dlsz~trlc defined
in a zoleoule
and a selection
of the cimular
The X-my
of considerable
of a clsoid
rigidity.
olmulsr
d.ichrolsm of gliotoxin
oonclude
that,
oaze,
analysis
of these
of gllotorin
(2) has
diene for the first Consideration
with allied
(1)
dichroism
sker dienes to the chirellty
the ohlrality
In thie
treatment
Charneg, Weiss end Wffer
the sig!
ehromophores. absolutely
1966)
of a theoreticsl
enunciated
oisold
22 April
evidence
the rule Is et varlence
time
of the
has led us to with experimental
obzervetione The rule associated (-
states
(1)~
with the lowest
260-280 $)
“A strong pozitlve
frequency
means the presence
in the sense of a rl&t-handed ie Indicative left-handed
This is associated lowest frequency
the dihedral
tzist.” angle
diene
absorption,
3139
band
diene chromophore tzisted
A strong negative In gliotorin,
Cotton effect ze find
L CjC6C7/C6C7C8 being
with a strong positive cieoid
diene ebsorptlon
of e cisoid
helix.
of the left-handed tziet,
cisoid
Cotton effect
a
14’ (2).
C-D. peak in the region
of
FE.1
*
C.D. ourw~w That for
reeordodla (3).
ham uardto du'ivothinxwult are th00.
#liotoxln hu ken ndetendnod on s
BoruulJousnblobrogrph ad aooorbrwlththepublUhedou.rne major feataim ma a lar@ane@in at-PI0 negative
peak nom 233 7
'9"'a #mallZlO~~tivO hfiOOti0~ peak,
~lodlarlymill,at 340 7
at
Ito
a poriflw pati 310
Y-
The peak at 233 9" -
attrlbnto to tr&Atlon~ arrrooiatod with the dlmlphide-bridged p%peraBInodione nyBtemmino0fourothermolooulo~oontaillin#thiB etruotural rlrment&or similar0.9. in thin retion(2,)). ¶%a pa& oooursat nomwhat~lon#er wavelength than wouldbe -0t.d
for
abrorption due to the peptidegoupm In 8 dikotopiporaslna (4). Thle rnw reflectboth tha opaaialdiaporltion of the two pi& dthres~otto
eaoh otherad
mw
the proxiudtyoftha diuulphida brld&a.
Again,the trua baud oentremy ba at &ortrr,wrvelength, the twver W-6
whereit door due to oontigaity with . poaitlvaband
of
higherfrequenoy. The poaitin peak near 270 4" in the C.D. ourvoof gliotoxln lo in the regionwhorethe oontribution from tha lowoatmorg of a ciaoidskewdionewouldbe expeotedto occur (1).
bud
TransforlMtion
of gliotoda,Fig. 3a, to dehydrogliotoxin, Fig. 3b, involveaconversion
No.27
3111
of the oyolohbxadibnb an-try
am
Two obntrbr of
one.
dbrtroybd, a hydroxyl @oup bbing lout in the w-ebb,
FQa 3a mid )b,
but the dibulphidb-@brabin~dionb
rin#
byEtOm ib Mt
8ubtraotion of the C.D. data of dbhydrogliototi
affbotbd.
that of &Lotoxin dib,lb,
ring to UI awn&i0
V,,lb6S
intmdaobd
bhould thbn rbwal
from
thb OontribUtion of thb bkbW
this i# mbnkbd bJ Z-OtatOrjbffbOt#
U’i#iD#
fX’OS
bbndme
uwnatlo
FIG.2
6
Ae ohown in Fig. poblfive ma@itudb
the
2, ewh a diffeI*mcb
pbak at cimr
260 ‘4”)
At - 10,
with that bxpeated from the
bblibf
that thie
That of gliotoxln
absorption
oonteinb
which is albo present 10s E - 3.61 (5). low @twral
oumb contain6
Am_
in dethlogliotoxin,
origin
through the baie
poeitioa
F’lg. 3~s ,%g.
m&on
a&
rbinforcb
in the dienb ay6tbm.
- 270 7’
~btd@ZOdsfbiO~iOtO~~,
absorption
in
U-V. epeotra
dibnb.
h.ee lte
L band
eonel~tbnt
bn IEOlatbd
(6).
log G - 3.64 (5) Am, 3,
= 29 hOWE
Od,
Ps
No.27
It abaorptloa
16
not to
diffloult
~oribe
the pm&tire of Rg.
2 to the lrft-
h6nded 6ker dieB0.
Thin, however, would constitute
au iniringemcmt
of the rule
In certain
aeewd brin#
revealed by the diffOIWBCe o~rw
dlohrola
(1).
to violate
the mla
them IBto like.
theOmtiCi%lly
dieno
(7),
the rule dth
regazd to ri(g.
(8) and the
CI6jOrity Of 6rperiIWBtti ObEem6tiOnE On the other hsnd, the
666unption6 Underlying the mle
It i6,convenient Imd ln6trwtive 6hip PtWen
BOwever,
at leacrt, it appear6 to be Ebundlg biued
the pC66ibl6 existence of other anomdo~6
the fmdamntal
C.D. re6Ultr hav6
Because of these examples, we at fir6t explored
t0 6UppCr.t it6 OOlTeCtEle66. d
caaee
end 6peclal effect6 have been invoked to
the porrd'bility of inverting for the oiroid
other
rCtatiOBd
Ettrmgfh
di66y6lMtlriC ChrO6lCphCre by meen
CR]
uempb6
appear
resultfrom
gllotoxlB
do aUgg66t that
rarrrnt examination.
to illrutrate the relation-
and dihedral Pgle
0 in 6
Of a pOlar dia@aEl, a6 in ng.
4a.
No.27
3143
(ii)
(i)
h
sa@rlentarepresenting
The lobe
intended as descriptive be a line et al. --
only,
of anti-egmetry,
the looun of but the null
an shorn,, g
TM* vierpoint
between the rotatory the oisoid the oarbony
diane,
properties
impliee,
the optical
sywnetric
in ketones.
Althou&
with the second-order activity
strengths
seem8 reasonable
alragr,
too clear
a distinotlon
ohlorvphorea,
chromophorea
suoh u
repmoente&by
it hss been stated
(9) that
of such a ohromophora ia to be
dia8ymrmtry of a oarbonyl
is merely induced by its
the ranges of rotational therefore,
perhaps,
of disrrmtric
11, - - the high degree of dlsamtry contrasted
at 0 = 0’ till
m
one aa8um8n with Hoeomits
and perturbed
poup
line
in the figulv
di~egnwwtry of the ~hromaphon,need
(1) that only the inherent
be oonaidered.
CR]
au~otmdin~”
of the two classes
to suggest
stituenta a, b, o end d, F’ig. 4(b)(i),
for rhlah in faot,
overlap.
that the preeenoe of subwill
modify the dichroio
It,
No.27
3144
lb~~orptlo:~~of the diene syetem, not 60 drastically
ll(p of ttie lobee in the polar dlagrmn, but nuffiolentlg diaporiti,n
of the lobes
relative
to 8 - O’,*
be at @ - 8’ aud no longer these circumstances, a p0miti.w observad
a line
of era&
a left-handed
ohirditg
Cotton effect
as llluntrated
rifeoting
the rotatory
wested
then the dlene rule from X-ray structure
We
of o( -phe:Llaudrene
feel *
losea
l
(cc
4(b)(ll)
with
aud aa
asywnetry lr capable
for
has been deduoad by cir&lar
end lrvopimaric
absolute
The pauoity
of
geometry of
diohroiao
ir
of the anomalous behaviour
acid (7) 10 warranted and we of the latter.
structure
oompounda would prove moat valxeble In thle
value.
the absolute
inepectlon
of
dlene in the way
much of ite
analysis
that oloaer
C-D. data with detailed
oertalntle~
could be aaaociated
of a clsold
intend to oarr~ out an X-ray analgala
#elected
UndOT
antl-ametry.
in Fig.
peripheral
propertiea
oompounds In which this rmiortUMb.
1100 would then
in @lotoxin. We are aware that if
evidence
to rotate the
the amount of rotation The null
depending on the nature of a, b, c and d.
the
go to Invert
analyses
Correlation
of
of other carefully
In resolving
the un-
Irltuation.
Footnote: A hint aa to the poselbilltg of Invoking such an explanation resulted from plotting the values of (4, vereun dihedral engle for 1,2-iiohloropropane, listed by Kirkwood Gal. (IO) end considering the lnfluewe of molecular symmetry on the resulting polar diagrem. Aaymaettic perturbation of a dissgrmnetrlo ohromophore will, in anoral, alter uhequa’lly the ahepes as well as the an&adisposition of the lobes of Fig. 4a. Footnote: A recent rtudy of the C.D. of d-phellandrene down to -15O’C has revealed no change in si@ (11). Such n&&t have been expects&if, as suggested (12), the obserkd results at 2040% depend on a thermal balance betveen equatorial and axial oonformatlons.
316
No.27
The Msulllde
ChrOmODhOre
In the gliotoxin a dlssymmetrlo
the group Cl-&&c3
chronophore with a left-handed
skewness being indicated dominant influence disulphide
molecule,
by the dihedral
of dihedral
frequency
the trsnsltion
is observed
At
= 0.4 at 340
a8 an inflexion,
At = 0.3,
disulphide
absorption
cieoid
feature
on this
here
the molecule
determined
the
frequency
chirality
but whether Adjacent
mey well have a perturbing
chromophore as suggested Absolutely
“r’
appears
In gliotoxin,
of the lowest
with left-handed
at 340
to the negative
Is dominated by the skew sense remains unclear+
diene.
valuable
at 310 "r" (14).
band is associated
(13),
In gliotoxin,
shoulder
corresponding
C.D. in the region
asymmetric elements within influence
towards O”.
A second negative
‘3”’
of the
of Calvin &t.
perceptible
curve,
The
band of the chronophore
~100’
as a barely
c - 200 on the U.V. abeorptlon C.D. peak,
LCSS/SSC = 14O.
in magnitude as the angle is
end decreases
reduced from the open chain value of
the elm
angle
the degree of
angle on the U.V. absorption
where It is shown that the lowest
negative
chirality,
group is demonstrated by the results
moves to longer wavelengths
constitutes
in the case of the
model
compounds
would
be
also.
References 1.
A. Moscowits, E. Charney, U. Weiss end H. Ziffer, Q, 4661 (19611.
2.
10 F. Beechsm, Jo Fridrichsons Letters - accompanying paper.
3.
8. Herrmann,
4.
L. J. Saidel,
5.
J. D. Dutcher, J. R. Johnson and W. F. Bruoe, J.A.C.S., (1945).
and A. LicL.
R. Hodees and A. Taylor, Arch.
Blochem.
Biophys.,
J.A.C.S.,
Yathleson,
Tetrahedron
J. Chem. Sot., 4315 (1964). 2,
45 (1955). 3,
f-l36
No.27
3146
6.
J. R. Johnson and R. Buohauau, J.A.C.S.,
7.
i;g~;~Burgstshler, 0
8.
A.
9.
10.
C.
Burley
fi. Ziffer
-
private
P. &abbe, O&ioal Bgnlo Chemistrs,
ad
5
2103 (1953).
U. Weiss, J.I.c.s.9
g
4660
oo~ioationo
Rotatory Disuersion end Circular Mohroism Holden-Dw, Sau Frauoisoo (19651, p.180.
1. 1. Wood, 1. Flckett
end J. 0. -hod,
in
JO C&em. PRY0.) $g.,
561 (1952)e 0.
Roremau
snd C. A. &ela,
Tetrahedron
Letters,
lo.,
3037
“’
(1965).
12.
S. Ziffer,
13.
J. A. Barltrop,
14*
C. Ejerassi, H. Wolf and E. Bunnenberg, J.A.C.S., &, 4552 (1962) 6,S-thiootio acid will have a dihedral angle ora26O (se X-qy data on 1,2-dithiolane-4-carboxylio acid, 0. Foss and 0. Tjmslaud, Acta Ohem. Soand., 12, 1810 (1958)) end therefore oonutltutes the nearest availane oomparison dth gllotoxin in this respect.
-
E. Charney and U. Weiss,
J.LC.S*,
P. Y. Hayes aud 1. Caldn,
2,
J.A.C.S.,
2961 (1962). &
4348 (1954).