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New Catalysts for the Synthesis of Nucleosides.

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PI
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PI
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r71
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[91
Chem. SOC. 96, 7255 (1974): b) srn- and unri-bishoino-p-benzoquinone:
J . Hrlfrr, A. Yogcc., and A. S. Drridinq. Helv. Chim. Acta 55, 1003
(1972): G. L. Brrchunuri, R. A . RupharI. and R. Taylor. J. C. S. Perkin
I IY73. 373: J. E. Heller. A . S . D r d i n q . B. R. O'Connor, H . E. Simnfori.~,
C . L. Buchunan. R. A. Raphorl, and R. Tarlor. Helv. Chim. Acta 56.
272 (1973): C . B. Chaplro and A . S. Drridinq, ibid. 57. 873 (1974).
K . Zahn and P. Ochuat, Liebigs Ann. Chem. 462. 72 (1928): B. Schriirlrr.
Dissertation, Universitit Miinchen 1965. We thank Prof. J . Sauer, Universitat Regensburg, for informing us of this work carried out under
his supervision.
E . Vogrl. W Klug, and A. Brruer. Org. Syn., in press.
E . Vogrl and W A. Boll, Angew. Chem. 76, 784 (1964): Angew. Chem.
internat. Edit. 3.642 (1964): E . Voqrl. W A . 8611, and M. Biskup, Tetrahedron Lett. 1966, 1569.
J . F. Bunnett, Quart. Rev. Chem. SOC. 12, I (1958); F. Pietra. ihid.
23, 504 ( 1969).
B. Brllruu and N. L. Weinhcq. J. Amer. Chem. SOC.8S, 2525 (1963):
cf. also. electrochemical methoxylation of furans: N. Elming. Advdn. Org.
Chem. 2. 67 (1960).
For conversion of 1.6-bridged [lO]annulenes into tricyclo[4.4.1 .O'."lundecane derivatives ([4.4.I]propellanes) see D . Ginsburg: Propellanes. Verlag
Chemie, Weinheim. in press.
H . Giinrhrr: NMR-Spektroskopie. G. Thieme Verlag, Stuttgart 1973,
pp. 365ff.
E. W Garbisch. Jr., J. Amer. Chem. SOC.87, 4971 (1965).
heterocycles with 1-0-acetyl-2,3,5-tri-O-benzoyl-P-~-ribofuranose (2) in 1.2-dichloroethane with 0.1 equiv. of a solution
of (3) or of ( 6 ) in benzene. On prolonged standing at 2 2 T ,
or on boiling for ca. 4 h, in addition to trimethylsilyl acetate
( 5 ) 2,3,5-tri-O-benzoyl-P-~-ribofuranosyl
perchlorate (or trifluoromethanesulfonate) is probably formed, which reacts with
( I ) to give 4-0-silylated uridine-tri-0-benzoate ( 4 ) .
U
OBz
New Catalysts for the Synthesis of Nucleosides[']
By Helmut Vorbriiggen and Konrad Krolikiewicz[*]
Reaction of silylated heterocycles with protected 1-0-acyl
or 1-0-alkyl sugars in the presence of Friedel-Crafts catalysts
like SnCI4 usually gives high yields of nucleosidesI2- 31, but
workup is often complicated by the formation of emulsions
and colloids.
As we have recently observed14],the easily prepared trimethylsilyl perchlorate (3)15],which is formed as an intermediate
in the AgCIO4 methodI6], as well as trimethylsilyl trifluoromethanesulfonate (6)"' show the properties of strong Lewis
acids and are suitable as Friedel-Crafts catalysts. We have
therefore reacted silylated uracil ( I ) as well as other silylated
( 4 ) HzO
Since new ( 3 ) or (6) is generated during this reaction
catalytic amounts of (3) or (6) are usually sufficient. The
workup with NaHC03/CH2C12 with saponification of ( 4 )
is very simple and gives uridine-tri-O-benzoate in ca. SO'%,
yield.
The analogous reactions, which are summarized in Table
1, demonstrate that this new modification of the silyl-HilbertJohnson reaction gives in analogy to the SnC14 methodI2-31
the desired natural P-nucleosides in high yields.
Table I . Reaction of silylated heterocycles with I -O~acetyl-2,3.5-tri-O-benzoyl-~-D-ribofuranosef 2 ) in 1.2-dichloroethane.
Conditions
Product
Heterocycles
(silylated)
Catalyst
uracil
0.1 equiv. ( 3 )
82"C/6 h
uridine-2'.3'.5'tri-0-benzoate
80 [a]
I 38--l40
uracil
0.25 equiv. ( 3 )
22"C/7 d
uridine-2'.3'.5'tri-@benzoate
76
138-140
cytosine
I equiv. ( 6 )
82"CJl h
cytidine-2',3',5'
t ri-0- benzoate
90
amorphous
2-thio-6azauracil [b]
0.1 equiv. ( 3 )
82"C/3 h
2- N-(2,3,4.6-tetra0-acet yl-p- D-glucopyranosyl)-3-thio2H-1.2,4-triarin-5-one
67
221 -223 [2]
N-benzoyladenine
0.1 equiv. ( 3 )
82T/7 h
adenosine rcl
81
230--232
2-pyridone
0.1 equiv. ( 6 )
82"CjZ h
I -(2,3.5-tri-O-benzoyl-P-D-ribofuranosyl)-2-pyridone
86
136-1 38 [ 2 ]
lumazine
01 equiv i l l )
24 C / 2 4 h
lumarine-riboside [d]
64
154--155
[a]
[b]
[c]
[d]
Ill
[XI
The analogous reaction in acetonitrile gave the same yield.
Reaction with 1,2.4,6-penta-O-acetyl-~-D-glucopyranose.
After saponification with C H 3 0 H / N H 3(22"C/16 h) and recrystallization from CH,OH/Hl (2:1).
After saponification with C H 3 0 H / N H 3 (24-C.184 h) and recrystallization from C,H,OH/i-PrOH.
['I
Dr. H. Vorbriiggen [**] and K. Krolikiewicz
Research Laboratories of Schering A.G.. Berlin/Bergkamen
1 Berlin 65. Postfach 6503 I I (Germany)
[**I Author to whom inquiries should be directed.
A n g m . Chem. iniernat. Edit. / Vol. 14 f 1975 J I No. 6
Procedure:
T o 10mmol of bissilylated !umazineLS1and 5.04g (IOmmol)
(2) in 50ml 1,2-dichloroethane, 1 mmol (6)"' (2ml of a stan42 1
dard solution in benzene) was added and the reaction mixture
stirred for 24 h a t 24 "C under argon. After shaking with ice-cold
NaHC03 solution, drying (NazS04) and evaporating, 6.5 g
of amorphous homogeneous lumazine-tri-0-benzoyl-riboside
was obtained, which was stirred with CH30H/NH3 for 84 h
at 24°C. After evaporation, 100ml H 2 0 was added and the
aqueous solution extracted with ether. Evaporation of the
aqueous phase afforded 3.2 g crude lumazine-riboside, which
was extracted with 200 ml boiling ethanol. Concentration
to 50 ml and addition of 150 ml isopropanol gave, in several
crops, 1.9 g (64%) lumazine-riboside, m.p. 154-1 55 "C (Ref.
[S]: 182-189°C).
Received: March 10. 1975 [Z 200 IE]
German version: Angew. Chem. 87, 417 (1975)
CAS Registry numbers:
( I ) . 10457-14-4: ( 2 ) . 6974-32-9: ( 3 ) . 18204-79-0;
( 6 ) . 27607-77-8; uracil. 66-22-8; cytosine. 11-30-7:
2-thi0-6-azauraci1, 626-08-4 : N-benzoyladenine. 4005-49-6 ;
2-pyridone. 142-08-5: lumazine. 487-21-8;
uridine-2'.3',5'-tri-O-benzoate,1748-04-5: cytidine-2'.3'.5'-tri-Obenzoate, 31652-74-1 ; 2-(2,3.4.6-tetra-O-acetyl-~-u-glucopyranosyl)-3thio-2H-1.2.4-triazin-5-one.
29725-44-8; adenosine. 58-61-7; 1-(2.3.5-triO-benzoyl-P-~-ribofuranosyl)-2-pyridone,
51 16-31-4;
lumazine-riboslde, 34097-18-2; 1,2.3,4,6-penta-O-acetyl-~-glucopyranose.
604-69-3
[I]
[2]
[3]
[4]
[S]
[6]
171
[8]
Synthesis of Nucleosides, Part 16; Reactions with Silyl Esters of Strong
Acids. Part I.-Part I5 cf. Ref. 141.
U . Niedbulla and H . Vorbriiggen, Angew. Chem. 82. 449 (1970); J. Org.
Chem. 39. 3654, 3660, 3664. 3668, 3673 (1974).
F . M! Lichrentholer, P. Voss. and A. H e e d , Tetrahedron Lett. 1974,
2141.
H . Vurhriiggen and K . Krolikiuwic.2, Angew. Chem. 87, 251 (1975); Angew.
Chem. internat. Edit. 14, 255 (1975).
C.Eaborn, J. Chem. SOC.1955. 2517: U . Wannugar and W Liehr, Angew.
Chem. 69. 783 ( 1 957).
H . Vorbriiggrn and P. Strehlke. Chem. Ber. 106. 3039 (1973).
H . C . Marsmann and H . G . Horn. Z . Naturforsch. 27b, 1448 (1972).
G . Rirzmann and W Pfleiderrr. Chem. Ber. 106, 1401 (1973).
[3 f 21-Cycloadditions of Mesoionic 1,3-Oxathio-4ones to Alkynes. A New Entry to the Furan Series[**]
By Hans Gotthardt, Michael C. Weisshuhn, and Karl Dorho~er[']
The 1,3-oxathiolylium-4-olate system of type ( 3 ) , a new
mesoionic 6 n arene"], is presumably too unstable to be
detected at room temperature. We have now been able to
produce (3) in situ from thiocarbonyloxyacetic acids and
to trap it by [3 21-cycloaddition.
If a benzene solution of phenyl(piperidinothiocarbony1oxy)acetic acid ( ( I ) , R=C,H,,N)[Z1 is heated to 7 G 8 O " C for
3 h with 5.9 equivalents of acetic anhydride in the presence
of 1.2 equivalent of methyl propiolate, then COS is liberated
with formation of methyl-5-phenyl-2-piperidinofuran-3-carboxylate (2a)I3', m. p. 74--76°C (further examples are given
in Table 1).
In the initial step of this new furan synthesis, the action
of acetic anhydride or dicyclohexylcarbodiimide on ( I )
Table I . Furans ( 2 ) from ( I ) and alkynes (reaction temperature 60-80°C).
Furan
(Zui
(ZbJ
f2c)
(2d)
422
Yield
[XI
3
2
34 [b]
37 [b], 67 [c]
C02CH2
CaH5
COCH,
C*HsCO
COzCH,
COzCH3
COCH,
ChHs
ChHsCO
0.5
51 [c]
}
:{
::;
H
COzCH,
COZCHI
C02CHa
5
8
52 [b]
49[b]
12h)
Pyrrolidino
H
COzCH3
COzCHa
COlCHs
0.5
3.5
55 [c]
60 [b]
SCHJ
COICH,
COzCHa
1
80
(?i)
(21)
[c]
[a] All furans were analyzed and characterized by spectroscopy.
[b] With acetic anhydride as cyclization agent.
[c] With dicyclohexylcarbodiimide as cyclization agent.
appears to promote elimination of water to form the 1,3-oxathiolium-4-olate ( 3 ) . As symbolized by the resonance structure (3b), the mesoionic 6n arene (31, which can only be
described in terms of zwitterionic resonance formulas, can be
formally regarded as a carbonyl ylide.
r
The second reaction step involves cycloaddition of the
mesoion (3) in positions 2,5 to activated alkynes, forming
nonisolable primary adducts ( 4 ) which rearomatize to the
furan derivatives (2) after elimination of COS. These reactions
are comparable with, e. g., 1,3-dipolar cycloadditions of
sydnonesI4I, munch none^^^^, 1,3-dithiolylium-4-0lates[~~,
and
1,3,2-oxathiazolylium-5-olates[71
to alkynes.
Received: March 11, 1975 [Z201 I € ]
German version: Angew. Chem. 87. 416 (1975)
CAS Registry numbers:
( I ) . R=piperidino, 54932-50-2; ( I ) . R=morpholino, 54932-51-3:
[ I ) . R=pyrrolidino. 54932-52-4; i l l , R=SCH,, 54932-53-5;
( 2 0 ) . 54932-54-6; ( Z b ) , 54932-55-7; ( 2 ~ )54932-56-8:
.
( Z d ) , 54932-57-9: (Ze). 54932-58-0; ( 2 f ) . 54932-59-1 :
/2g). 54932-60-4: /.?hi. 54932-61-5; ( A ) , 54932-62-6;
[ Z j ) . 54932-63-7 ; methyl propiolate. 922-67-8 ;
dimethyl 2-butynedioate. 762-42-5; 4-phenyl-3-butyn-2-one. 1817-57-8:
1.4-diphenyl-2-butyne-l,4-dione.
1087-09-8
131
K. Dorhofer
Institut fur Organische Chemie der Universitat
8 Munchen 2, Karlstrasse 23 (Germany)
[ +] T o whom correspondence should be addressed
["I This work was supported by the Fonds der Chemischen lndustrie
H
Piperidino
Time
PI
Morpholino
[2]
[*] Priv.-Doz. Dr. H. Gotthardt [ +]. DipLChem. M. C. Weisshuhn, and
R"
(2fi
(2g)
[I]
(21
R'
f2ri
+
H'..C'= C-K"
R
[a1
[4]
[5]
161
171
Mesoionic arenes: M! Baker and Ct: D . Ollis. Quart. Rev. Chem. SOC.
I / , 15 (1957); M . Ohfa and H . Kuro in J. P. Snxder: Nonbenzenoid
Aromatics. Academic Press, New York 1969, Vol. I. p. 117.
Preparation of ( 1 ) by analogy with: M . Marell. Acta Chem. Scand.
14, 677 (1960).
60-MHz 'H-NMR (CDCls): r=8.32 (br. s, 6H), 6.43 (mc, 4H), 6.29
(s, OCH,), 3.21 ( s , 4-H), 2.92-2.45 (m. CsHs).
R . Huisgen, H . Gorrhardt. and R . Crasher. Chem. Ber. 101, 536 (1968);
R . Huisgen and H . Gorthardr. ibid. 101, 1059 (1968).
R . Huisgen, H . Corthardr, H . 0. Barer, and F . C. Schaufer, Chem. Ber.
103. 261 I (1910).
H . Gotthardr and B. Christ!, Tetrahedron Lett. 1968. 4747; 1.3-dithiolylium-4-olates bearing nitrogen-, sulfur-, and oxygen-containing substituents on C-2 have already been subjected t o 1.3-dipolar cycloaddition:
M . C . Weisshuhn and H. Gorrhordr, unpublished experiments.
H. Gofrhardf,Chern. Ber. 105, 196 (1972).
Anyen.
Chmi. iiirernut. Edir. i Vol. 14 ( 1 9 7 5 ) ! N o . 6
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