Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
1999-03-18
2001-01-16
Geist, Gary (Department: 1623)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C536S027110, C536S124000
Reexamination Certificate
active
06175005
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a process for the preparation of a cyclic ether containing an O-silylated hydroxyl group.
2. Prior Art
Recent widespread development of genetic engineering attracts people's attention to various kinds of nucleic acid derivatives as functional substances or pharmaceuticals. Thus, intensive studies are being made on derivatives of nucleosides constituting a basic skeleton of nucleic acids, as starting or intermediate materials for the production of nucleic acid derivatives. Technology developed up to date is primarily concerned with deoxyribonucleic acids. Whilst a deoxyribonucleoside contains a primary hydroxyl group and a secondary hydroxyl group in its molecule, a ribonucleoside in ribonucleic acids, which is now increasingly utilized, has three hydroxyl groups including one primary hydroxyl group and two secondary hydroxyl groups. Thus, as a starting material for the synthesis of RNA, a compound having its 2′-hydroxyl group previously protected similar to a deoxyribonucleoside is suited. A 2′-O-silylated ribonucleoside, which is important among others, has been hitherto prepared by a method in which a compound having its highly reactive primary hydroxyl group protected is first prepared. The other two hydroxyl groups are silylated and the product is separated by chromatography. With this method, however, it is difficult to improve selectivity so that the desired compound is only obtained by toublesome treatments.
Similar to the ribonucleoside, an aldopyranose compound has one primary hydroxyl group and a plurality of secondary hydroxyl groups. When only the primary hydroxyl group at its 6-position and the secondary hydroxyl group at its 4-position are to participate a reaction, it is desired that the other reactive hydroxyl groups be protected. However, there is no method which can easily introduce a protective group to the hydroxyl groups other than those at 4- and 6-positions.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide a process which can easily produce a hydroxyl groups-containing cyclic ether compound in which at least one of the hydroxyl groups except a primary hydroxyl group thereof and its neighboring secondary hydroxyl group is protected.
In accordance with the present invention there is provided a process for the preparation of an 0-silylated hydroxyl group-containing cyclic ether represented by the following formula (4)
wherein R
1
represents a substituent which does not react with a hereinafter described difunctional silicon compound, Y
1
and Y
2
each represent a methylene group, a hydroxymethylene group or a methylene group having a substituent which does not react with a hereinafter described difunctional silicon compound, t and q are each a number of 0 or 1, and R
4
, R
5
and R
6
each represent an aromatic group or an aliphatic group, provided that, when
Y
1
and Y
2
each represent a hydroxymethylene group, the hydroxyl group thereof is converted into OSiR
4
R
5
R
6
where R
4
,
R
5
and R
6
have the same meaning as above,
characterized in that a hydroxyl groups-containing cyclic ether represented by the following formula (1)
wherein R
1
, Y
1
, Y
2
, t and q have the same meaning as above, is reacted with the difunctional silicon compound represented by the following formula (2)
R
2
R
3
SiX
1
2
(2)
wherein R
2
and R
3
each represent an aromatic group or a branched aliphatic group having at least 3 carbon atoms and
X
1
represents a residue of an acid,
then with a monofunctional silicon compound represented by the following formula (3)
R
4
R
5
R
6
SiX
2
(3)
wherein R
4
, R
5
and R
6
have the same meaning as above and X
2
represents an eliminative group,
and then with hydrofluoric acid in the presence of a base.
The present invention also provides a process for the preparation of a 2′-O-silylated ribonucleoside represented by the following formula (6)
wherein B represents an unprotected or protected nucleic acid base and R
4
, R
5
and R
6
each represent an aromatic group or an aliphatic group,
characterized in that a ribonucleoside represented by the following formula (5)
wherein B has the same meaning as above,
is reacted with a difunctional silicon compound represented by the following formula (2)
R
2
R
3
SiX
1
2
(2)
wherein R
2
and R
3
each represent an aromatic group or a branched aliphatic group having at least 3 carbon atoms and
X
1
represents a residue of an acid,
then with a monofunctional silicon compound represented by the following formula (3)
R
4
R
5
R
6
SiX
2
(3)
wherein R
4
, R
5
and R
6
each represent an aromatic group or an aliphatic group and X
2
represents an eliminative group,
and then with hydrofluoric acid in the presence of a base.
The present invention further provides a process for the preparation of an O-silylated aldopyranose compound represented by the following formula (8)
wherein R
7
represents a substituent which does not react with a hereinafter described difunctional silicon compound,
at least one of R
8
and R
9
represents OSiR
4
R
5
R
6
(where R
4
, R
5
and R
6
each represent an aromatic group or an aliphatic group) with the proviso that, when one of R
8
and R
9
does not represent OSiR
4
R
5
R
6
, that R
8
or R
9
represents a substituent which does not react with a hereinafter described difunctional silicon compound,
characterized in that a hydroxyl groups-containing cyclic ether represented by the following formula (7)
wherein R
7
has the same meaning as above, R
8
and R
9
each represent a hydroxyl group or a substituent which does not react with a hereinafter described difunctional silicon compound, with the proviso that at least one of R
8
and R
9
represents a hydroxyl group,
is reacted with the difunctional silicon compound represented by the following formula (2)
R
2
R
3
SiX
1
2
(2)
wherein R
2
and R
3
each represent an aromatic group or a branched aliphatic group having at least 3 carbon atoms and
X
1
represents a residue of an acid,
then with a monofunctional silicon compound represented by the following formula (3)
R
4
R
5
R
6
SiX
2
(3)
wherein R
4
, R
5
and R
6
have the same meaning as above and X
2
represents an eliminative group,
and then with hydrofluoric acid in the presence of a base.
Other objects, features and advantages of the present invention will become apparent from the detailed description of the preferred embodiments to follow.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS OF THE INVENTION
The hydroxyl groups-containing cyclic ether represented by the general formula (1) includes ribonucleoside and aldopyranose compounds.
In the general formula (1), R
1
is a substituent which is not reactive with a difunctional silicon compound of the general formula (2). Such substituents include protected or unprotected nucleic acid bases, sugar compound residues, alkyl groups, alkoxy groups, substituted amino groups, substituted mercapto groups, acyl groups, acyloxy groups and various other groups and are suitably selected according to the desired compound.
In the general formula (1), Y
1
and Y
2
each represent a methylene group (CH
2
), a hydroxymethylene group (CHOH) or a substituent which does not react with the above-described difunctional silicon compound. The substituent which does not react with the above-described difunctional silicon compound may be various groups as described above.
The symbols t and q each represent a number of 0 or 1. When t and q are 0, (Y
1
)t and (y
2
)q each represent a direct bond. When t and q are 1, the two carbon atoms adjacent each of Y
1
and Y
2
are bonded to each other through Y
1
and Y
2
.
In the case of a ribonucleoside expressed by the general formula (5), the substituent B is a substituent which does not react with the above-described difunctional silicon compound. Examples of such substituents include unprotected or protected nucleic acid bases comprising a pyrimidine base and a purine base. The glycoside bond by w
Crane L E
Director--General of Agency of Industrial Science and Technology
Geist Gary
Lorusso & Loud
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