Vol.
64, No.
3, 1975
BIOCHEMICAL
CONFORMATION STUDIED
OF BY
‘H
I-
AND
NUCLEAR
of
Pharmaceutical
Research
Research
Received
April
and
Ajinomoto
Katsumi
Ajisaka
Inc.,
magnetic phenomena
about
the
structure
sides
and
nucleotides
nucleosides some
derivatives deam
of them
of adenosine
inase
(8). *
of enzymes, 1 -Deazakinetin
To whom
Osaka,
Suzuki-cho,
Kawasaki,
553
Japan
210
Japan
effect and spin-lattice relaxation-time adopts the w-conformation similar to (freely rotating) component. The results I is stabilized presumably through a group.
resonance
(NMR)
spectroscopy
has been
employed
successfully
conformation
(2-5).
were
thus
about
shown
found (I)
involving
to lie
to assume
active the
in anti-conformation -
anti
resonance
valuable
including bond
in the
conformations
can
be substrates
to act
as a substrate
syn
nucleo-
of purine region
(5,6); for
and
information
substances
N-glycosidic
predominantly the
multiple
to provide
of biologically
Conformation
was
of I - (II) and 3-deazaadenosines have been examined. Features of I, II, and III have similar conthe 4’-C - 5’-C bond are prefer-
(2,5),
and
only
the
adenosine
(6).
I-Deazaadenosine number
and
in solution
whereas
Japan
16,1975
entially Nuclear Overhauser --gauche-gauche. measurements demonstrate that II predominantly that of I, whereas that of III has a greater anti suggest that the F--conformation in II as wxas hydrogen bond between the 3-N and 5’-hydroxyl
relaxation
060
Tori* Fukushima-ku,
SUMM4RY: ‘H nuclear magnetic resonance spectra (III) together with adenosine (I) in dimethylsulfoxide coupling constants indicate that the furanose rings of formational preferences and that conformations about
Nuclear
AS (I)
Sapporo,
Ltd.,
Co.,
SOLUTION
Mizuno
Kazuo
8, Co.,
COMMUNlCATlONS
SPECTROSCOPY
University,
and
Kamisaku
Laboratories,
Yoshihisa
Hokkaido
Ueyama
Masako Centraf
and
Shionogi
IN
RESONANCE
Sciences,
Laboratory,
RESEARCH
3-DEAZAADENOSINES
Kitano
Masako Shionogi
BlOPHYSlCAL
MAGNETIC
Shigeru Faculty
AND
inquiries
(II) showed including
ability
cAMP-dependent
ribofuranoside should
the
protein
was found
be addressed.
Copyright o 1975 b,y Academic Press, Inc. All rights of reproduction in any form reserved.
996
to exhibit
kinase potent
or an activator (7) and cytokinin
for
5’-nucleotidase activity
in
a
Vol.
64,
the
No. 3,1975
tobacco
activity
BIOCHEMICAL
pitch (9).
callus
In sharp
bioassay
(nearly
inactive)
it has been
shown
that
kinetin
not
clear.
on the and
However,
nature
trend
of this
study
(III)
II
of
and
copy
including
III
found
systems. (9)
and
Moreover,
that
3-deaza-
reasons
in each
between the
each
above
pair
pair
could
enzyme
starting
is of course
points
shed
light
systems.
Thus,
of this
conforma-
II
of isomers.
that
in a preliminary of I for
Overhauser
effect
form,
comparison (NOE)
N-glycosyl
as studied
(10)
and
conforma-
by ‘H NMR
spin-lattice
spectros-
relaxation
time
measurements. AND
NMR
The
preparation
of
of these
samples
HA-100
and
in [ 2H,]
dimethylsulfoxide
was
MEASUREMENTS
II
an XL-loo-15
HA-100
in the
frequency-swept
technique
with
RESULTS
AND
The observation
NMR
180°-
III
(ca. -
‘H
30“).
reported
NMR
spectra using
containing
1%
NOE
about TMS
sequences
10%
taken
The with
(w/v)
as an internal (10)
mode.
MHz
procedures. were
experiments
TMS-locked
at 100 pulse
followed
spectrcmeter
and
operating 7-90“
(12)
grade.
(DMSO)
temperature
XL-loo-15
and
NMR
probe
on the
(11)
analytical
ordinary
similar
were
(1).
to be logical
reported,
with
nuclear
MATERIALS
out
pairs
are
same
toward
thought
interesting
together
the
behavior are
communication
tions
for
comparison
contrasting
of these
In this
arises
enzyme
reagent
as a cytokinin
conformational
3-deazaadenosine
tional
(Tt)
general
ineffective
antileukemic
derivatives
in these
as an antileukemic
COMMUNICATIONS
potent
phosphate
or activators
is inactive
RESEARCH
II shows
3-deazaadenosine
is also
this
BIOPHYSICAL
Furthermore,
substrates
III
ribofuranoside Whether
(I).
contrast,
to be poor
AND
were
a Varian
degassed
solutions
standard
at
performed
T, measurements
use of an inversion-recovery
in the
pulse
Fourier
on the
were
by the
and
purity
carried
transform
mode.
DISCUSSION spectral
may conformational
parameters
be taken
obtained
as reflections
preferences
in the
in DMSO that rapid
997
the
furanose equilibria
are
listed rings (4,5)
in Table of
I.
This
I, 11, and III
with
approximately
have
Vol.
64, No.
3, 1975
Table
BIOCHEMICAL
I.
Chemical Shifts, Spin-lattice
AND
BIOPHYSICAL
RESEARCH
6, Spin-coupling Constants, Relaxation Times, T,
J,
5 (*0.01)
Proton
COMMUNICATIONS
and
T, (kO.5
I+
II+
0.50
III ---
0.72
0.32
---
0.32
0.63
0.72
0.66
5.98d
0.55
0.58
0.39
4.73q
4.33t
0.26
0.26
0.25
5.47d
5.36d
c
0.55
0.65
3’-H
4.21q
4.17m
4.19t
0.29
0.29
0.25
3’-OH
5.19d
5.13d
c
0.58
0.65
c
4’-H
4.02q
4.02q
4.079
0.43
0.43
0.38
5’-HA
3.60m
3.58brm
3.67brm 0.14
0.15
0.12
5’-H8
3.72m
3.68brm
3.71brm
5’-OH
5.44m
6.04brm
4
0.55
0.66
c_
6-NH,
7.35brs
6.45brs
0.11
0.13
1-H
---
6.42d
---
2-H
8.18s
7.80d
7.79d
3-H
D-w
---
7.46d
8-H
8.37s
8.25s
8.72s
l’-H
5.93d
5.92d
2’-H
4&q
2’-OH
J (Go.2 1 -H,2-H
---
2-H,3-H
-mm
---
0.09
7.1 5.9
2’-H,3’-H
5.1
4.8
5 .o
3’-H,4’-H
3.0
2.6
3.0
4’-H,5’-HA
3.8
-3
.gd
4’-H,S-HB
3.3 -12.2
-3 -(-)12d-
.gd
3’-H,3’-OH
CL
---
5.8
6.4
6.4 4.7
II
Hz)
6.1
2’-H,2’-OH
2.74
8.59brs
1 ‘-H ,2’-H
5’-HA,5’-HB
I
set)
-3.5d -3.5d
Multiplicities: s : singlet, d: doublet, t : triplet,
-(-)12d 6.2 4.2
q : m : 4 E
E Obtained by computer analysis using the IAOCNB program. - Obtained by the first-order analysis. C Not determinable owing to exchanging of OH signals. d Not exactly determinable owing to line broadening of 5’-H probably kO.5 Hz or less.
998
quartet, multiplet, and br: broad signal
signals:
errors
are
Vol.
64, No.
60%
3, 1975
of the
2’-endo
preferentially lower
by -ca.
The
-0.4
ppm
results
signals than
may
about
of I and
ring
In order pairs
from
8-H
the signal
and
to confirm
exercised
in interpretation
In the present
following taken
to each somewhat
most
important
order:
2’-H,
17%
as an index
because
in the
fields
by -ca.
latter.
These
conformations
region
by the
close
at
proton
different
deshielding
fixed
in II,
as described quantitative f&l
results
of the
proximity
and
‘) and
well
from
those
3-N
lone-
to the
(lo), (13)
reflect
time-averaged
of
and
f,,(3)
in
to the
much
and
f,(5’-OH) rapid
inverting
should
(14)
observed
on the
f3(2’)
of their
be
systems.
structures
equilibria
for present
caution
in II and
III
measured
pertinent
in rotating
must
were
results
known
the
f&l’)
interactions
The
evidence
III (see
in
conformations,
in considerably
large
conformations.
interactions
their
NOE
observations
extents,
16%
of distance
because
more
a conformation
is deshielded
results
The
in II,
to prove
other
assumes
1 . As has been
NOE
in slight
seem
approximation
similar
nucleosides.
of NOE
also,
f2(5’-OH)
The
II adopt
assumptions,
in these
(2,3,10).
though
extents,
that
II is situated
above
in Fig.
cases
time-scale
the
signals
are shown
although
of the
are
II appear
at higher
signal
III
of III
appear
1 and
bonds
corresponding
corresponding
assumptions
8-H
- 5’-C
of I and
to the
two
COMMUNICATIONS
moiety.
of proton
l),
that
to 2’-H
due
former
to the
whereas
of I and
discussion
Fig.
by the
due
the signal
of the
RESEARCH
in the 4’-C
signals
does
due
linkage,
base,
The
arising
BIOPHYSICAL
conformations
(4,5). than
2’-H
AND
that
ppm
does
that
of the
NOE
and
+0.35
N-glycosyl II,
furanose
most
(5),
be explained
the
pairs
form
gauche-gauche -___
fields
in III.
BIOCHEMICAL
in
f, (1’)
in the
I,
14%
and
r between
the
furanose-ring above.
f&2’)
were
III
in
anomeric
the
for the
999
(see
have
Fig.
large
1).
and
been
treatment
relative only
compounds
proton
moieties
However,
estimations
present
decreased
in the
This
may
8-H
order
as the
considered
first
to be similar
by Eq.(A)
(10)
may
give
between
8-,
l’-,
and
distances enhancements
of 8-H;
be
Vol.
64, No.
3, 1975
BIOCHEMICAL
HO
OH
Adenosine
(I)
AND
BIOPHYSICAL
RESEARCH
HO
OH
1 -Deazaadenosine
HO
1.
OH
(III)
Structures and NOE i-l-l +j-H indicates the j-H signal when
ris/r.,t a Thus
the
ratios
rs,2l/rs,,l
in I,
1 .lO,
respectively.
Moreover,
Psyn
is approximately
given
Psyn
= ’ - Panti
II,
by Eq .(B)
Enhancement Values (*2%) in DMSO: that an NOE, fj (i), was observed on the i-H frequency was saturated.
[ fi tt)/ f; ts)1‘I6
and the
x
(II)
a Not determinable owing to close signal positions or exchanging.
3-Deazaadenosine
Fig.
COMMUNICATIONS
III
were
proportion
estimated of time
according
3f*(1’)/13je(1’)
to be about spent
to Son
-
1000
(A)
in the
et al.
fe(2')
-
1 .15,
1 .19,
and
syn-conformation
(3);
f,(3')1
(f-9
Vol.
64, No.
Then,
3, 1975
we
can
respectively suggest than
BIOCHEMICAL
obtain neglecting
that I),
whereas
in III
Spin-lattice
The
0.58
set,
nism,
weak
listed
occurs
to each
smaller
T, value
respectively)
probably
with
those
well
as those
described with
for can
through
2-H, above.
NOE
more
other
and
III
RESEARCH
to be about
component
COMMUNICATIONS
0.87,
0.89,
in II.
These
results
similar
to that
observed
syn-conformation anti
I.
II,
BIOPHYSICAL
f,(5’-OH)
than
I has,
and
0.84,
strongly
of I (or more
or the
rotation
fyll
about
the
freely.
times
in Table
similar
I,
adopts
relaxation
as also
III.
for
III has a greater
bond
virtually
the
II predominatly
N-glycosyl
sides,
values
Psyn
AND
T, were The
also
T, values
from
compound
1 ‘-H
in III
for
8-H
and
all
set)
than
as showing
all
furanose
those that
effective
in III,
the
Detailed
analyses
of the
results
between
protons
except
becomes
interactions
for
to compound,
(0.39
be interpreted
determined
furanose-ring
protons that
in I and
another result with
of the
for
are l’-H
II (0.55
relaxation which
nucleo-
in and
mecha-
is in harmony
T, measurements
protons
will
as
be reported
in future. In conclusion,
it is found
equilibria
for
is ordered
as II > I > III,
N-glycosyl tion
these
nucleosides,
conformation
of a hydrogen-bond
important
role
that
in stabilizing
the
both and
former
that two,
in the syn between
syn-
the
and
anti-conformations -
the decrease II as well
region.
in proportion as I, predominatly
We would
5’-hydroxyl
the syn-conformations
group
like
to suggest
and
the 3-N
of I and
exist
in rapid
of F
to anti
adopting that atom
the
the
forma-
plays
an
II.
REFERENCES 1.
2. 3.
4.
Part XIX of Syntheses of Potential Antimetabolites. Part XVIII, see Kitano, Nomura, A., Mizuno, Y., Okamoto, T ., and Isogai, Y. In submission to Biochem. Biophys . Res. Commun. Davis, J. P. and Hart, P. A. (1972) Tetrahedrong, 2883-2891; Davis, (1972) Tetrahedron 28, 1155-l 165; and references therein. Son, T.-D., Guschlbauer, W., and Gueron, M. (1972) J. Amer. Chem. 94, 7903-7911; Son, T.-D. and Chachaty, C. (1973) Biochim. Biophys. 335, 1-13; G&on, M., Chachaty, C., and Son, T.-D. (1973) Ann. N. Acad. Sci. U. S. A. 222, 307-323; and references therein. Nanda, R. K ., Tewari, R., Govil, G ., and Smith, I. C. P. (1974) Can. Chem. 52, 371-375; and references therein.
1001
S.,
J. Sot. Acta Y. J.
P.
Vol.
64, No.
5.
3, 1975
Sarma, R. H., Lee, M. (1974) J. Amer.
BIOCHEMICAL
C.-H., Chem.
AND
BIOPHYSICAL
Evans, F. E., Yathindra, Sot. 96, 7337-7348; and
6.
RESEARCH
N., and references
COMMUNICATIONS
Sundaralingam, therein.
Long, R. A., Townsend, L. B., Miles, D. W., Eyring, H ., and Robins, R. K. Abstracts of Papers, 161st National Meeting of the American Chemical Society, Los Angeles, Calif. March 28-April 2, 1971, ORGN 112. 7. Miller, L. P. Personal communication. 8. Mizuno, Y., Kitano, S., and Nomura, A, (1975) Chem. F’harm. Bull. (Tokyo) In press. 9. Mizuno, Y. and Kitano, S. In preparation. 10. Noggle, J. H. and Schirmer, R. E. (1971) The Nuclear Overhauser Effect: Chemical Applications, Academic Press, New York. 11 . Itoh, T., Kitano, S., and Mizuno, Y. (1972) J. Heterocyclic Chem. 9, 465-470. 12. Mizuno, Y ., Tazawa, S ., and Kageura, K . (1968) Chem . Pharm . Bul I. (Tokyo) 3, 2011-2017. 13. Saunders, J. K. and Bell, R. A. (1970) Can. J. Chem. 48, 512-514. and Ogino, T. (1973) Tetrahedron Lett. 14. Horibe, I ., Tori, K., Takeda, K., 735-738.
1002
64, No.
3, 1975
BIOCHEMICAL
CONFORMATION STUDIED
OF BY
‘H
I-
AND
NUCLEAR
of
Pharmaceutical
Research
Research
Received
April
and
Ajinomoto
Katsumi
Ajisaka
Inc.,
magnetic phenomena
about
the
structure
sides
and
nucleotides
nucleosides some
derivatives deam
of them
of adenosine
inase
(8). *
of enzymes, 1 -Deazakinetin
To whom
Osaka,
Suzuki-cho,
Kawasaki,
553
Japan
210
Japan
effect and spin-lattice relaxation-time adopts the w-conformation similar to (freely rotating) component. The results I is stabilized presumably through a group.
resonance
(NMR)
spectroscopy
has been
employed
successfully
conformation
(2-5).
were
thus
about
shown
found (I)
involving
to lie
to assume
active the
in anti-conformation -
anti
resonance
valuable
including bond
in the
conformations
can
be substrates
to act
as a substrate
syn
nucleo-
of purine region
(5,6); for
and
information
substances
N-glycosidic
predominantly the
multiple
to provide
of biologically
Conformation
was
of I - (II) and 3-deazaadenosines have been examined. Features of I, II, and III have similar conthe 4’-C - 5’-C bond are prefer-
(2,5),
and
only
the
adenosine
(6).
I-Deazaadenosine number
and
in solution
whereas
Japan
16,1975
entially Nuclear Overhauser --gauche-gauche. measurements demonstrate that II predominantly that of I, whereas that of III has a greater anti suggest that the F--conformation in II as wxas hydrogen bond between the 3-N and 5’-hydroxyl
relaxation
060
Tori* Fukushima-ku,
SUMM4RY: ‘H nuclear magnetic resonance spectra (III) together with adenosine (I) in dimethylsulfoxide coupling constants indicate that the furanose rings of formational preferences and that conformations about
Nuclear
AS (I)
Sapporo,
Ltd.,
Co.,
SOLUTION
Mizuno
Kazuo
8, Co.,
COMMUNlCATlONS
SPECTROSCOPY
University,
and
Kamisaku
Laboratories,
Yoshihisa
Hokkaido
Ueyama
Masako Centraf
and
Shionogi
IN
RESONANCE
Sciences,
Laboratory,
RESEARCH
3-DEAZAADENOSINES
Kitano
Masako Shionogi
BlOPHYSlCAL
MAGNETIC
Shigeru Faculty
AND
inquiries
(II) showed including
ability
cAMP-dependent
ribofuranoside should
the
protein
was found
be addressed.
Copyright o 1975 b,y Academic Press, Inc. All rights of reproduction in any form reserved.
996
to exhibit
kinase potent
or an activator (7) and cytokinin
for
5’-nucleotidase activity
in
a
Vol.
64,
the
No. 3,1975
tobacco
activity
BIOCHEMICAL
pitch (9).
callus
In sharp
bioassay
(nearly
inactive)
it has been
shown
that
kinetin
not
clear.
on the and
However,
nature
trend
of this
study
(III)
II
of
and
copy
including
III
found
systems. (9)
and
Moreover,
that
3-deaza-
reasons
in each
between the
each
above
pair
pair
could
enzyme
starting
is of course
points
shed
light
systems.
Thus,
of this
conforma-
II
of isomers.
that
in a preliminary of I for
Overhauser
effect
form,
comparison (NOE)
N-glycosyl
as studied
(10)
and
conforma-
by ‘H NMR
spin-lattice
spectros-
relaxation
time
measurements. AND
NMR
The
preparation
of
of these
samples
HA-100
and
in [ 2H,]
dimethylsulfoxide
was
MEASUREMENTS
II
an XL-loo-15
HA-100
in the
frequency-swept
technique
with
RESULTS
AND
The observation
NMR
180°-
III
(ca. -
‘H
30“).
reported
NMR
spectra using
containing
1%
NOE
about TMS
sequences
10%
taken
The with
(w/v)
as an internal (10)
mode.
MHz
procedures. were
experiments
TMS-locked
at 100 pulse
followed
spectrcmeter
and
operating 7-90“
(12)
grade.
(DMSO)
temperature
XL-loo-15
and
NMR
probe
on the
(11)
analytical
ordinary
similar
were
(1).
to be logical
reported,
with
nuclear
MATERIALS
out
pairs
are
same
toward
thought
interesting
together
the
behavior are
communication
tions
for
comparison
contrasting
of these
In this
arises
enzyme
reagent
as a cytokinin
conformational
3-deazaadenosine
tional
(Tt)
general
ineffective
antileukemic
derivatives
in these
as an antileukemic
COMMUNICATIONS
potent
phosphate
or activators
is inactive
RESEARCH
II shows
3-deazaadenosine
is also
this
BIOPHYSICAL
Furthermore,
substrates
III
ribofuranoside Whether
(I).
contrast,
to be poor
AND
were
a Varian
degassed
solutions
standard
at
performed
T, measurements
use of an inversion-recovery
in the
pulse
Fourier
on the
were
by the
and
purity
carried
transform
mode.
DISCUSSION spectral
may conformational
parameters
be taken
obtained
as reflections
preferences
in the
in DMSO that rapid
997
the
furanose equilibria
are
listed rings (4,5)
in Table of
I.
This
I, 11, and III
with
approximately
have
Vol.
64, No.
3, 1975
Table
BIOCHEMICAL
I.
Chemical Shifts, Spin-lattice
AND
BIOPHYSICAL
RESEARCH
6, Spin-coupling Constants, Relaxation Times, T,
J,
5 (*0.01)
Proton
COMMUNICATIONS
and
T, (kO.5
I+
II+
0.50
III ---
0.72
0.32
---
0.32
0.63
0.72
0.66
5.98d
0.55
0.58
0.39
4.73q
4.33t
0.26
0.26
0.25
5.47d
5.36d
c
0.55
0.65
3’-H
4.21q
4.17m
4.19t
0.29
0.29
0.25
3’-OH
5.19d
5.13d
c
0.58
0.65
c
4’-H
4.02q
4.02q
4.079
0.43
0.43
0.38
5’-HA
3.60m
3.58brm
3.67brm 0.14
0.15
0.12
5’-H8
3.72m
3.68brm
3.71brm
5’-OH
5.44m
6.04brm
4
0.55
0.66
c_
6-NH,
7.35brs
6.45brs
0.11
0.13
1-H
---
6.42d
---
2-H
8.18s
7.80d
7.79d
3-H
D-w
---
7.46d
8-H
8.37s
8.25s
8.72s
l’-H
5.93d
5.92d
2’-H
4&q
2’-OH
J (Go.2 1 -H,2-H
---
2-H,3-H
-mm
---
0.09
7.1 5.9
2’-H,3’-H
5.1
4.8
5 .o
3’-H,4’-H
3.0
2.6
3.0
4’-H,5’-HA
3.8
-3
.gd
4’-H,S-HB
3.3 -12.2
-3 -(-)12d-
.gd
3’-H,3’-OH
CL
---
5.8
6.4
6.4 4.7
II
Hz)
6.1
2’-H,2’-OH
2.74
8.59brs
1 ‘-H ,2’-H
5’-HA,5’-HB
I
set)
-3.5d -3.5d
Multiplicities: s : singlet, d: doublet, t : triplet,
-(-)12d 6.2 4.2
q : m : 4 E
E Obtained by computer analysis using the IAOCNB program. - Obtained by the first-order analysis. C Not determinable owing to exchanging of OH signals. d Not exactly determinable owing to line broadening of 5’-H probably kO.5 Hz or less.
998
quartet, multiplet, and br: broad signal
signals:
errors
are
Vol.
64, No.
60%
3, 1975
of the
2’-endo
preferentially lower
by -ca.
The
-0.4
ppm
results
signals than
may
about
of I and
ring
In order pairs
from
8-H
the signal
and
to confirm
exercised
in interpretation
In the present
following taken
to each somewhat
most
important
order:
2’-H,
17%
as an index
because
in the
fields
by -ca.
latter.
These
conformations
region
by the
close
at
proton
different
deshielding
fixed
in II,
as described quantitative f&l
results
of the
proximity
and
‘) and
well
from
those
3-N
lone-
to the
(lo), (13)
reflect
time-averaged
of
and
f,,(3)
in
to the
much
and
f,(5’-OH) rapid
inverting
should
(14)
observed
on the
f3(2’)
of their
be
systems.
structures
equilibria
for present
caution
in II and
III
measured
pertinent
in rotating
must
were
results
known
the
f&l’)
interactions
The
evidence
III (see
in
conformations,
in considerably
large
conformations.
interactions
their
NOE
observations
extents,
16%
of distance
because
more
a conformation
is deshielded
results
The
in II,
to prove
other
assumes
1 . As has been
NOE
in slight
seem
approximation
similar
nucleosides.
of NOE
also,
f2(5’-OH)
The
II adopt
assumptions,
in these
(2,3,10).
though
extents,
that
II is situated
above
in Fig.
cases
time-scale
the
signals
are shown
although
of the
are
II appear
at higher
signal
III
of III
appear
1 and
bonds
corresponding
corresponding
assumptions
8-H
- 5’-C
of I and
to the
two
COMMUNICATIONS
moiety.
of proton
l),
that
to 2’-H
due
former
to the
whereas
of I and
discussion
Fig.
by the
due
the signal
of the
RESEARCH
in the 4’-C
signals
does
due
linkage,
base,
The
arising
BIOPHYSICAL
conformations
(4,5). than
2’-H
AND
that
ppm
does
that
of the
NOE
and
+0.35
N-glycosyl II,
furanose
most
(5),
be explained
the
pairs
form
gauche-gauche -___
fields
in III.
BIOCHEMICAL
in
f, (1’)
in the
I,
14%
and
r between
the
furanose-ring above.
f&2’)
were
III
in
anomeric
the
for the
999
(see
have
Fig.
large
1).
and
been
treatment
relative only
compounds
proton
moieties
However,
estimations
present
decreased
in the
This
may
8-H
order
as the
considered
first
to be similar
by Eq.(A)
(10)
may
give
between
8-,
l’-,
and
distances enhancements
of 8-H;
be
Vol.
64, No.
3, 1975
BIOCHEMICAL
HO
OH
Adenosine
(I)
AND
BIOPHYSICAL
RESEARCH
HO
OH
1 -Deazaadenosine
HO
1.
OH
(III)
Structures and NOE i-l-l +j-H indicates the j-H signal when
ris/r.,t a Thus
the
ratios
rs,2l/rs,,l
in I,
1 .lO,
respectively.
Moreover,
Psyn
is approximately
given
Psyn
= ’ - Panti
II,
by Eq .(B)
Enhancement Values (*2%) in DMSO: that an NOE, fj (i), was observed on the i-H frequency was saturated.
[ fi tt)/ f; ts)1‘I6
and the
x
(II)
a Not determinable owing to close signal positions or exchanging.
3-Deazaadenosine
Fig.
COMMUNICATIONS
III
were
proportion
estimated of time
according
3f*(1’)/13je(1’)
to be about spent
to Son
-
1000
(A)
in the
et al.
fe(2')
-
1 .15,
1 .19,
and
syn-conformation
(3);
f,(3')1
(f-9
Vol.
64, No.
Then,
3, 1975
we
can
respectively suggest than
BIOCHEMICAL
obtain neglecting
that I),
whereas
in III
Spin-lattice
The
0.58
set,
nism,
weak
listed
occurs
to each
smaller
T, value
respectively)
probably
with
those
well
as those
described with
for can
through
2-H, above.
NOE
more
other
and
III
RESEARCH
to be about
component
COMMUNICATIONS
0.87,
0.89,
in II.
These
results
similar
to that
observed
syn-conformation anti
I.
II,
BIOPHYSICAL
f,(5’-OH)
than
I has,
and
0.84,
strongly
of I (or more
or the
rotation
fyll
about
the
freely.
times
in Table
similar
I,
adopts
relaxation
as also
III.
for
III has a greater
bond
virtually
the
II predominatly
N-glycosyl
sides,
values
Psyn
AND
T, were The
also
T, values
from
compound
1 ‘-H
in III
for
8-H
and
all
set)
than
as showing
all
furanose
those that
effective
in III,
the
Detailed
analyses
of the
results
between
protons
except
becomes
interactions
for
to compound,
(0.39
be interpreted
determined
furanose-ring
protons that
in I and
another result with
of the
for
are l’-H
II (0.55
relaxation which
nucleo-
in and
mecha-
is in harmony
T, measurements
protons
will
as
be reported
in future. In conclusion,
it is found
equilibria
for
is ordered
as II > I > III,
N-glycosyl tion
these
nucleosides,
conformation
of a hydrogen-bond
important
role
that
in stabilizing
the
both and
former
that two,
in the syn between
syn-
the
and
anti-conformations -
the decrease II as well
region.
in proportion as I, predominatly
We would
5’-hydroxyl
the syn-conformations
group
like
to suggest
and
the 3-N
of I and
exist
in rapid
of F
to anti
adopting that atom
the
the
forma-
plays
an
II.
REFERENCES 1.
2. 3.
4.
Part XIX of Syntheses of Potential Antimetabolites. Part XVIII, see Kitano, Nomura, A., Mizuno, Y., Okamoto, T ., and Isogai, Y. In submission to Biochem. Biophys . Res. Commun. Davis, J. P. and Hart, P. A. (1972) Tetrahedrong, 2883-2891; Davis, (1972) Tetrahedron 28, 1155-l 165; and references therein. Son, T.-D., Guschlbauer, W., and Gueron, M. (1972) J. Amer. Chem. 94, 7903-7911; Son, T.-D. and Chachaty, C. (1973) Biochim. Biophys. 335, 1-13; G&on, M., Chachaty, C., and Son, T.-D. (1973) Ann. N. Acad. Sci. U. S. A. 222, 307-323; and references therein. Nanda, R. K ., Tewari, R., Govil, G ., and Smith, I. C. P. (1974) Can. Chem. 52, 371-375; and references therein.
1001
S.,
J. Sot. Acta Y. J.
P.
Vol.
64, No.
5.
3, 1975
Sarma, R. H., Lee, M. (1974) J. Amer.
BIOCHEMICAL
C.-H., Chem.
AND
BIOPHYSICAL
Evans, F. E., Yathindra, Sot. 96, 7337-7348; and
6.
RESEARCH
N., and references
COMMUNICATIONS
Sundaralingam, therein.
Long, R. A., Townsend, L. B., Miles, D. W., Eyring, H ., and Robins, R. K. Abstracts of Papers, 161st National Meeting of the American Chemical Society, Los Angeles, Calif. March 28-April 2, 1971, ORGN 112. 7. Miller, L. P. Personal communication. 8. Mizuno, Y., Kitano, S., and Nomura, A, (1975) Chem. F’harm. Bull. (Tokyo) In press. 9. Mizuno, Y. and Kitano, S. In preparation. 10. Noggle, J. H. and Schirmer, R. E. (1971) The Nuclear Overhauser Effect: Chemical Applications, Academic Press, New York. 11 . Itoh, T., Kitano, S., and Mizuno, Y. (1972) J. Heterocyclic Chem. 9, 465-470. 12. Mizuno, Y ., Tazawa, S ., and Kageura, K . (1968) Chem . Pharm . Bul I. (Tokyo) 3, 2011-2017. 13. Saunders, J. K. and Bell, R. A. (1970) Can. J. Chem. 48, 512-514. and Ogino, T. (1973) Tetrahedron Lett. 14. Horibe, I ., Tori, K., Takeda, K., 735-738.
1002
