with carbon tetrabromide and triphenylphosphine in the presence of lithium ... 5'-Azido-5'-deoxyuridine was eluted after elution of triphenylphosphine oxide.
sTRY LETTERS, pp. 977-980,
■97う
.
Ptlb■ ished
by the Chemica■
sOciety of
」apan
SIMPLE METHOD FttR THE SYlqTHESIS OF 5:― AZ IDO-51-DEOXYRIBONUCLEOSIDES
TSu〕 ■aki
HATA, Isamu YAⅣ P010T07 and Mitsuo SEKINE
LabOratory of Chemistry for Natural Products′
Faculty of science
Tokyo lnstitute of Techno■ ogy Ookayama′ Meguro― ku′ Tokyo 152
Az■ do
group was
nuc■ eos■ des by one―
■ntroduced
step reaction
selective■ y to 5:― position of
using carbon tetrabromide′
tripheny■
―
phosphine′ and lithium azid9.
reports have appeared on the regiospecific reactions of the 51-hydroxyl 1) phosphorylation′ ■grOtp Of the sugar moiety of nucleosides inc■ uding tritylation′ ■ ‐ Severa■
2)
■ ation,3) and ha.。 genation.4) Azido― nucleoside is one of the key intermediates 譲 ジ .■
n:nuc■ eos■ de chem■ stry and is usua■ ■y synthes■ zed by the reaction of the nuc■
:=tOsylate and meta■ th●
azide.5)
Recent■ y, Castro and his co― workerS6)have reported
reactiOns of a■ coho■ s or glucopyranos■ de w■ th phosphon■ um sa■ ts We a■ so found that the a■ kylthio group cOu■ d be
=Jloflsodium azideo
≡,eleCtiVely and smooth■ y to the 5:― position of nucleosides by use diSu■ fides 'F■
I
eos■ de
and tri― n― butylphosphine under neutra■ conditions。
■n
the presence
■ntroduced
of dia■ ky■
7)
In this commun■ cation′ we w■ sh to report a s■ mple methoa for
■ntrOduction
of
■ 1■ ￨い e azido group to the 5:― position of nuc■ eosides by the reaction of nuc■ eosides 三二 With
Carbon tetrabromide and tr■
H°
pheny■ phosphine in the presence of
B
ヤ
N30
■ithium
B
」LJ
HO
R
HO de base, B=ndC′ e“ ′
R二
H or OH
R
azide。
Chomistry Letters, 1975
978
For examp■ ё′ carbon tetrabromide (3.mmo■ (2 mmo■ )
tripheny■ phosphine
dimethy■ fOrmamide (10 m■
for 24 hr.
) was added to a mixture of uridine
(2.6 mmol)′ and lithium azide (6 mmo■
The mixture was stirred continuously at room temperature
)。
and the solvent was
The reaction was quenched by addition of methano■
removed under reduced pressure. ge■ 。 E■ ution
) in dry
The res■
dua■ o■ ■
was applied to a co■ umn of s■ lica―
oroform and methano■ (581 V/V)。
was performed with a mixture of ch■
51-Azido-5:― deoxyuridine was e■ uted after elution of tripheny■ phosphine oxide.
lected and concentrated under
Fractions containing 51-azido-51-deoxyuridine were co■ reduced pressure.
It was obtained in 92t yie■
confirmed by IR (2100 cm…
1′
d as white powdero
The structure was
azido group)′ UV′ and elemental analysis.
In this reaction′ it was found that increases
■n
the amounts of both carbon uridine and
tetrabromide and triphenylphosphine resulted in a mixture of the azido― 51-bromo-5:― deoxyuridine.
deoxy― N6_benzoy■
In a simi■ ar manner′ 51-azido-51-deoxythymidine7 51-azido-5:―
deoxy― N2_benzoylguanosine′
Tab■ e
Nuc■ eos■ de (mM)
lo
Unfortunate■
y′
5・ ―azido-51-
a guanosine derivative′
cou■ d not be obtained by this method.
SYNITHESIS OF 51-AZIDO-51… DEOXYRIBONUCLEOSIDES
CBr4
Ph3P
LiN3
time
yield
m.p.
(mM)
(HIM)
いr● 1)
(hr)
(2)
(° C)
U
2 ●〇
3
.〇 〇
2
.60
6.O
24
92
150-150.5(decomp.)
T
2 ●〇
2
.04
2 。04
lO.O
24
90
164.5-166.5
ABZ
1
1
.56
1
.56
7.5
24
56
171(decOmp。
CBZ
2・〇
2
.20
2
.20
lη .〇
23
45
η75-178(decomp.)
.5
U = ur■ dinef
ｒ 一
yields as shown in Tab■ e l.
e
and 51-azido-51-deoxy― N4_benzoylcytidine were obtained in reasonab■
一 一
adさ nOsine′
T = thymidine′
ABZ = N6_ム enzoy■ adenos■ ne
)
cBz = N4_benzoy■
cytidine. The reaction seems to prttceed through a phosphonium sa■ reacts with lithiun azide to form an intermediate 2.
t (1)WhiCh in turn
This intermediate further
reacts with nucleoside to afford a nucleoside phosphonium salt (3)which COnverts into 51-azido-5:― deoxyribonuc■ eoside and tripheny■ phosphine oxide.
―
―
Letters,
1975
﹄ｒ
Ｂ
３
Ｂ Ｃ ・ ， 一 Ｈ ＋ Ｐ
３ ｈ
Ｐ
→
ｒ ｌ Ｌ
Ph3 P + CBr4
1) [Ph3P CBr3]Nl
_」 」」上
(2) ure
ca―
B
2 + HOw
_喝
理
ｒ ａ
HO
HO
R
R
J HO
R
(3) 三l‐
thiS method′ the azidO group can be
introduced se■ ective■ y at the 5:― pOsitiOn
des under very m■ ■d cOnditiOns.
This method may be widely app■ icab■ e tO from the cOrresponding a■ cOho■ s in
■■31eOS■
C■
■■● Sl‐ ntnes■
3r=二 二 ic
synthesis.
_■ 3
■■
=
s Of az■ dO der■ vatives starting
authOrs w■ sh tO express the■ r thanks to Professor Teruaki
Couragement throughOut the 3■
■nvestigationo
Mukaiyama fOr
Thanks are a■ so due to Miss setsuko
i l.liss Yumiko lshizawa for the e■ ementa■ ana■ ys■ s。
111ご ュ ニ■
■■is
wOrk was partial■ y supported by grant from the Ministry
Of EducatiOn′
」apan.
REFERENCES a F.■
.■
evene and R.S.Tipson′
二 .I.ニ ュ
=i■ er′
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I.Iュ
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KoKato′ and
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lol′
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こ 」.P.I.verheyden
228,i1972).
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(b)ibid.′
37′
Chemistry Letters, 1975
980
5) (a)W.」 ahn′ ChemoBer.′
and
」。Chua′
RoK.Robins′
98′
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′27′
(b)JoPoHorwitz′
3045(1962),
(c)M.GoStout′
A.」 .Tomson′ M。 」 .Robins′
J.A.Urbanski′ R.K.〇 ■sen′ and
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ve′
ve′
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(b)BoCaStrO′
Y.Chapleur′
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′1409(1975)。
(Received
」u■ y
23, 1975)
