The optical rotatory dispersion of pyrimidine nucleosides

The optical rotatory dispersion of pyrimidine nucleosides

Vol. 19, No. 5, 1965 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS THEOPTICALROTATORY DISPERSIONOF PYRIMIDINE NUCLEOSIDES" T.L.V. Ulbricht,...

163KB Sizes 1 Downloads 40 Views

Vol. 19, No. 5, 1965

BIOCHEMICAL

AND BIOPHYSICAL

RESEARCH COMMUNICATIONS

THEOPTICALROTATORY DISPERSIONOF PYRIMIDINE NUCLEOSIDES" T.L.V.

Ulbricht,

T.R. Emersonand R.J. Swan

Twyford Laboratories,

London, England

and Westfield ReceivedApril19,

College, London, England

1965

Although the optical

rotatory

has been studied intensively

dispersion (ORD) of polynucleotides

in the last six years, little

work has

been done on their monomeric components (Yang and Samejima, 1963; Ulbricht

et al, 1.964).

of a-pyrimidine

Wehave previously

reported that the ORDcurves

nucleosides give negative Cotton effects,

p-anomers give positive

Cotton effects

(Ulbricht

whereas the

et al, 1964);

pyrimidine N3-nucleosides do not obey Hudson's Isorotation (Emerson & Ulbricht,

1964).

these compounds, a series of about forty examined.

Rules

In order to find what factors

sign and magnitude of the long wave-length Cotton effect

affect

the

produced by

such nucleosides have been

These include numerous derivatives

thymine, as well as cyclonucleosides,

hence

of uracil,

cytosine and

azapyrimidine nucleosides and

pseudouridines. Wefind that the w following noted;

factors:

of the Cotton effect

is influenced by the

1) the anomeric configuration

at C-11, as already

2) the position of substitution

pyrimidine

ring (e.g.,

6-pseudouridine,

small negative Cotton effect); heterocyclic

is reversed);

C-5' and O-2 @,5'-cyclouridine *Optical

which is a 25-glycoside,

3) substitution

nucleus (in A-azauridines

the Cotton effect

of the glycoside residue on the gives a

of N for CH in the

and &azaoytidines

4) formation of a third

the sign of ring, between

gives a negative Cotton effect).

Rotatory Dispersion of Nucleic Acid Derivatives,

643

Part III.

Vol. 19, No. 5, 1965

BIOCHEMICAL

The following

nature of the substituents

is little uridine

ring.

The fact that the magnitude of the Cotton effect of the sugar hydroqls

give very similar

azauridine triacetate)

in either ring,

is only slightly

but is sensitive

influenced by

to the configuration

at

For example, arabinosides (spongouridine,

cytosine arabinoside) give larger Cotton effects

ribosides (uridine,

and

indicates that hydrogen-bonding is not involved.

C-2' in the sugar. a = +294*;

(uridine

curves, as do azauridine and

The magnitude of the Cotton effect substitution

is not influenced by the

in the sugar ring or on the nitrogen-

influenced by acetylation triacetate

RESEARCH COMMUNICATIONS

observations were noted for the series of

The sign of the Cotton effect

P-nucleosides.

heterocyclic

AND BIOPHYSICAL

+117; cytidine),

(22,21-cyclouridine,

than

as do 02,Zt-cyclonucleosides

a = +266) (see Figure 1).

It seemsreasonable to assumethat the ORDresults must be related to the conformation of the chromophore with reference to the asymmetry in the sugar. obtained with

Of particular

relevance,

cycle-&hydroxyuridine

Whereas2,2'-cyclouridines

(a = +490) show similar

a larger amplitude) to that shown by uridine, effect

in Qs,5t-cyclouridines

We suggest, therefore, rotation

are the results

in which the conformation is fixed by

cgclonucleosides,

formation of a third ring.

therefore,

and 04,5'-

Cotton effects

(though of

the sign of the Cotton

and -thymidines is reversed (see Figure 1).

that in a nucleoside like uridine

about the -M-Cl' bond is theoretically

possible,

(I),

although

a preferred

conformation is adopted in which the oxygen atom on C-2 is directed away from the sugar ring,

as shown.

Formation of additional

between O-2 and C-2' or between a hydroxyl this conformation very little.

rings,

either

on C-4 and C-5' would change

However, to form an 02,5'-cyclonucleoside,

(molecular rotation at first extremum minus molecular *Amplitude a rotation at second extremum) is divided by 100 (Djerassi and Klyne, 1963).

644

Vol. 19, No. 5, 1965

BIOCHEMICAL

AND BIOPHYSICAL RESEARCH COMMUNICATIONS

+3 \

\

+? *-.

\

./“\

\

,

\

-1

‘\

...-..

\ ‘\

.’ I

\

‘\

‘\. x. ...~~~--~~‘~~~~.. . . . . . . . . . . . . . . . . ::.-:.z:,: \ .. ,;’ ; ./.. >. .-... - . ..-...-...-...-...-...-... _c--_--\ ‘.,, ;/ *. ‘.,.’ -----------/‘....,... 'i'------i i \ ,... ‘,

‘,

:

1:

.c’7\..

i

\-: ,/!

-2

?

i ‘\

‘\

‘.

i

\

.\ \

&

\

i ’



‘\

i

‘.

0

‘\

I \

‘\.

+1 -4 ‘9

\

I ,.,

! t ’

!

solvent:

‘i&J’

water

-3 I, ?20

I 240

.

1, 260

1 280

(

1, 3al

, 320

%/I

Fig.1. ORD curves of uridine @,5'-cycloth.~midiae (-+*.-); hydroxyuridine (-e-m).

a rotation

(..-**); C1~,2’-cyclouridine (---.) and 02,5'-cycle-4-

of about 180' about the -N-ClI' bond is required.

a comparison between the cyclo- and non cyoloaidinee although the chromophores may differ factor

does not in itself

(as their

lead to any drastic

In making

it is assumedthat

U.V. data indicate) alteration

of their

this ORD

behaviour.

I

ORDmeasurement8were madewith the Bellingham and Stanley/ Bendix-Ericsson Spectropolarimeter

'lPolarmatic

645

‘62”

at room-temperature

Vol. 19, No. 5, 1965

BIOCHEMICAL

AND BIOPHYSICAL

on aqueous (and a few methanolic) solutions

at'mex . of

RESEARCH COMMUNICATIONS

( with en optical

density

not more than 2).

It is hoped to publish full

details

elsewhere, together with a consideration of U.V. data (Clark and Tinoco, 1965), many kind individuals

of these and other results of the recent interpretation

and an acknowledgement to the

who have supplied us with compounds. REFERENCES

Clark, L.B., and Tinoco, I., Jr,, J. Amer. Chem. Sot., 3, 11 (1965). Djerassi, C., and Klyne, W., J. Chem. Sot., 2390 (1963) Emerson, T.R., and Ulbricht, T.L.V., Chem.& Ind., 2129 (1964). Ulbricht, T.L.V., Jennings, J.P., Scopes, P.M., and Klyne, W., Tetrahedron Letters, 695 (1964). Yang, J.T., and Samejima, T., J. Amer. Chem. Sot., 3, 4039 (1963).

646