The optical rotatory dispersion of purine nucleosides

The optical rotatory dispersion of purine nucleosides

BIOCHEMICAL Vol. 22, No. 5, 1966 AND BIOPHYSICAL RESEARCH COMMUNICATIONS Dispersion of Purine Nucleosides' B T.R. Emerson, R.J. Swan and T.L.V. U...

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BIOCHEMICAL

Vol. 22, No. 5, 1966

AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Dispersion of Purine Nucleosides'

B

T.R. Emerson, R.J. Swan and T.L.V. Ulbricht Xestfield

College, London, England and

Twyford Laboratories,

London, Englend

ReceivedJanuary 25, 1966 we have previously

reported that the Optical Rotatory Dispersion

(ORD) curves of a-purine nucleosides give positive the p-anomers give negative Cotton effects purine ~y-nucleosides 1964).

(Ulbricht

obey Hudson's Isorotation

Recently we presented preliminary

nucleosides, indicating

Cotton effects,

whereas

et al, 1964);

hence

Rules (Emerson and Ulbricht,

results

on a series of pyrimidine

that the sign and magnitude of the long wave-length

Cotton effects produced by these compoundscould be related to their conformation (Ulbricht

et al, 1965).

Further studies have confirmed these

conclusions and have madeit possible to propose a rule for predicting

the

sign of the Cotton effect

et al,

1966).

in pyrimidine

Wehave now examined fifty

results with E9-glycosides, nucleosides.

purine nucleosides, and report here our

including

cvclo-nucleosides

is excluded.

In many cases, complete ORDcurves are more difficult

purine nucleosides absorb intensely the use of very dilute

* Optical Rotatory Part IV: T.L.V. ai Dress.

aromatic

groups, which can influence the sign of the Cotton

to obtain with purine than with pyrimidine nucleosides.

necessitating

and azapurine

Consideration of compoundscontaining additional

systems (e.g. p-toluoyl Effect)

fursnose nucleosides (Ulbricht

in the ultra-violet

This is because (high e values),

solutions in the region near-h max.'

Dispersion of Nucleic Acid Derivatives, part V. Ulbricht, R.J. Swan& A.&i. Wchelson, Chem. Commun.,

505

BIOCHEMICAL

Vol. 22, No. 5, 1966

and because is

they

noticeably

purines

have

lower

following

the &g~

1) the anomeric

(N3,5'-cycloadenosine

one nucleoside

in which

the Cotton

relation

sign

of the

(D- or L-)

at the anomeric

carbon

The sign isopropylidene group

not

groups

position

in

the purine

8 in the heterocyclic effects

like

of adenosine

nucleosides

- suggesting,

has no major

between xylose

derivatives

(Ulbricht

effect et al,

If chromophore

1965;

Emerson

such ORD results with

by substitution

nucleus

(+azapurine

reference

the

stereochemistry

of acetyl

or of the 2'-OH of the

of N for

CH at

nucleosides

purinea).

give

The tri-O-acetyl

give

similar

curves

the pyrimidines,

that

to the parent

hydrogen-bonding

effect. effect

sugars,

considerably

this

as in P-L-compounds.

nor

In pyrimidine is

, since

by the nature

is

but no significant

of various

that

configuration

or by replacement

affected

of the Cotton

and arabinose.

the Cotton

not

as with

ring

to the optical

ring

of a In the

is probable

by the presence

on the Cotton

in either

as already

configuration it

to be general

and guanosine

influence

The magnitude substitution

effect

the corresponding

derivatives

Cotton

the same in a-D-

ring,

by

at c-l',

a positive

was positive;

in the sugar is also

configuration

had the opposite

influenced

It

by H or Cl.

substituents

Cotton

is

influenced

effect).

prove

atom is

is

gives

effect

will

effect

by formation

of the Cotton

of the sugar

most of these

in the m-conformation

the sugar

(p-L-adenosine)

for

effect

50-110.

of the Cotton

the nucleoside

of the Cotton

nucleosides;

in the range

factors:

ring

'ihe magnitude

rotations.

in pyrimidine

is

that

2) fixing

noted; third

than

the amplitude We find

the

small

AND BIOPHYSICAL RESEARCH COhtMUNlCATlONS

slightly

were

found

ribose,

p-nucleosides,

et al,

by

differences

including

higher

influenced

Pt-deozyribose,

the amplitude

in arabinosides

than

of

in ribosides

1966).

are related

to the oonfoxmation

to the asymmetry

506

in the sugar,

of the as suggested

BIOCHEMICAL

Vol. 22, No. 5, 1966

AND BIOPHYSICAL RESEARCH COMMUNICATIONS

for p,yrimidine nucleosides (Ulbricht rotation

and the insensitivity

et al, 1965,

1966),

to the configuration

Whereas, in pyrimidine nucleosides, steric groups on C-2' (and, to a lesser extent,

then the lower

at C-21 is understandable.

interaction

between the

those on C-5') and substituents

in position

2 of the pyrimidine ring (such as the carbonyl

effeotively

prevent free rotation

interaction

is greatly

(II)

atom.

The latter

forms will be small.

favoured, e.g., It

bona, such

reduced or absent in purines (Donahue and Trueblood,

Consequently the energy difference

1960).

&

about the glycosidic

group)

by electronic

between the m conformation will

(I)

and still

be

repulsion between N3 and the ring oxygen

is, of course, the &

conformation which is found in DNA,

in AMP (Kraut and Jensen, 1964) and in almost all

crystalline

nucleosides

(Sundaralingam and Jensen, 1965).

MO

OH

OM

Ho

I

II

The results obtained with c.vclQnucleosides, in which the conformation is fixed by formation of a third ring, interest.

Thus 8,5(-cycloadenosine

are of particular

(III)

(Xmx , 264 w), in which the . a&& conformation is fixed by a ring linking C-5' of the sugar to C-8 in the imidazole ring, has a negative Cotton effect

like other purine

P-nucleosides, but of larger amplitude (a - -183). 2~,:i1-isopropylidene-~3,5~-cycloadenosine which necessarily has the m effsct

iodide (IV)

On the other hand, (hmax., 272 q),

conformation, has a small positive

(a - +Yt) (see Figure 1).

Cotton

From other examples we know that the

507

BlOCHEMlCAL

Vol. 22, No. 5, 1966

isopropylidene

AND BIOPHYSICAL RESEARCH COMMUNICATIONS

group has no effect

on the sign of the ORD, and it should

the also be noted that theh max. of both cyclonucleasides falls *thin Rowever, in the cese of range of the compoundsstudied (248-279 w)+ the g3,5\-cyclonucleoside,

the possibility

that a change in the

chromophore is responsible for the change in sign cannot be excluded,

I-

IV

III The interpretation unsubstituted the first

of the curves given by giycosides of

purine (see fig.

2) is madedifficult

by the fact that

peak in the OEDcurve occurs at a wave-length very close to

theh max. (265 w)a

This suggests that this maximumin the U.V, is

due to an overlap of the absorption due to two transitions, of which is optically

active.

If the optically

at a wave-length lower the..nh-.,

the first

active

only one

transition

Cotton effect

were

would be

positive;

if it were at a wave-length higher thanAm= . , the first Cotton effect would be negative, The latter would be in accord with the results for substituted

of the transition

purine P-nucleosides, but since the direction

momentmay be different,

will not necessarily be the seme. the first

the sign of the Cotton effect

The absence of a real trough before

peek is reached suggests that the first

Cotton

effect

mey be

positive. It will

be noted that these unsubstituted

have two Cotton effects,

purine nucleosides

the second being negative.

one or both extreme of this second Cotton effect

508

Wehave observed

in a number of other

Vol. 22, No. 5, 1966

BIOCHEMICAL

*lo'-

:

AND BIOPHYSICAL RESEARCH COMMUNICATIONS

1."'1""1““1'

-4-6-

:

-a-lO-

I 250

200

i : / ] i ::: .:’ ‘.I ,..I....

solvent:

water I . . . . I 455 350

305 XCmp)

Fig.

1. ORD curves

of adenosine

8,5'-cycloadenosine tadenosine

iodide

(-);

(..**a*);

(-em*-

Sazaadenosine

*a*).

.-

/

HO

HP

250

-3 r HO

OH

200

(-a-*);

2',31-isopropylidene-N3,5'-cyclo-

-3

300

h(m$

350

2. OFtD curves of the J3-riboside, 2'4eoxyriboside and erabinoside of unsubstituted purine.

Fig.

nucleosicles in which measurementswere satisfactorily wave-lengths, e.g. 8-aaaadenosine (fig. 6-chloropurine.

l),

and various derivatives

The sign of the second Cotton effect

always negative in p-anomers (it

has

not

so far available).

509

extended to low of

appears to be

been observed in the wsnomers

BIOCHEMICAL

Vol. 22, No. 5, 1966

ORD measurements

were made with

Spectropolarimeter

"Polarmatic

rricsson (and

a few methanolic)

more than

solutions

the Bellingham '62"

(with

and Stanley/Bendix-

at room-temperature

an optical

density

on

aqueous

ath max. of not

2). It

elsewhere,

AND BIOPHYSICAL RESEARCH COMMUNICATIONS

is hoped

to publish

together

with

who have supplied

us with

1V.R. Lee and E.M. Acton to whoiomwe are particularly

full

a full

details

of these

scknowledgement

compounds. and their

results

to the msny kind

Many were

associates

and other

the gift

at Stanford

of Drs. Research

individuals L. Goodman, Institute,

indebted.

References and Trueblood, K.N., J. Mol. Biol., 1, 363 (1960), Donahue,.J., T.L.V., Chem. & Ind., 212 (1964). Emerson, T-R., and Ulbricht, &, 79 (1964 s . Kraut, J., and Jensen, L.H., Acta Cryst., Sundsralingam, M., end Jensen, L.H., J. Mol. Biol., u, 914, 930 (1965). Ulbricht, T.L.V., Jennings, J.P., Scopes, P.%, and Klyne, W., Tetrahedron Letters, 695 (1964). Ulbricht, T.L.V., Emerson, T.R., and Swan, R.J., Biochem. Biophys. Res. Comm., u, 643 0965). Ulbricht, T.L.V., Emerson, T-R., and Swan, R.J., Tetrahedron Letters, in press.

510