JPH03255083A - Novel antiviral agent and its production - Google Patents

Abstract

NEW MATERIAL:A compound of formula I (R1 is H, OH, amino, alkyl, halogen, alkoxy or mercapto; R2 and R3 are each H or amino). EXAMPLE:6-Aminopurine-9-2',3',4'-trideoxyglucopyranoside. USE:An antiviral agent. PREPARATION:A fusion is made using an appropriate coupling reagent between a purine compound of formula II and a compound of formula III (Ra is protective group for alcohol selected from H, acetyl, benzoyl and <=10C esters or protective group selected from benzyl, tetrahydropyranyl, ethoxyethyl ether, trityl, tert-butyldimethylsilyl and <=20C ethers; Rb is H or acetyl), thus freeing Ra from protection.

Description

Detailed Description of the Invention [Industrial Application Field] The present invention provides novel antiviral agents 2', 3', 4' -1-lyso- This invention relates to oxygluconucleosides and methods for producing the same.

[Prior Art] In recent years, various antiviral agents have been developed due to the rapid increase in diseases caused by viruses such as AIDS and hepatitis. ), AZT (azidothymidine), H
ACV (aciclovir) is known to be effective against SV (pure herpesvirus).

[Problem to be solved by the invention]

A common problem with previously developed antiviral agents is their limited antiviral spectrum. For example, ACV has no effect on the above-mentioned HIV, and AZT has no effect on H3V. In other words, certain antiviral agents are only effective against certain viruses.

Therefore, we have developed a new drug with a broader antiviral spectrum than the current one.
The development of new antiviral agents is awaited.

Furthermore, the fate of antiviral drugs is that if they are used continuously over a long period of time, resistant strains of the virus will emerge. Therefore, even though it is a highly effective drug, it is impossible to use it for a long period of time. Therefore, there is a need for the development of new antiviral agents with different action sites that can be used in combination with existing antiviral agents.

An object of the present invention is to provide a novel antiviral agent with new efficacy and a method for synthesizing the same.

1 2 [Means to solve the problem] General formula [IJ and - formula [H] (In the formula, R1 is a hydrogen atom, a hydroxyl group, or an amino group.

Alkyl group, halogen atom, alkoxy group.

(wherein, X is a hydroxyl group or an amino group, and Y is a hydrogen atom, an alkyl group, or a halogen atom) This is based on the discovery that a novel nucleic acid derivative represented by the following formula has antiviral activity.

The present invention provides a 2' 3 compound represented by the above general formula [I].
'4'-1-lysoxyglucoprine nucleosides and/or 2' represented by general formula [I]]
, 3', 4'-)lideoxyglucopyrimidine nucleoside F as an effective active ingredient, and a method for producing the same.

In the present invention, the purine derivative represented by the formula [rV] and the pyrimidine derivative represented by the formula [V] can be used as they are from the constituent components of inexpensive liponucleic acid, and The components can be chemically modified and used by well-known methods. Alternatively, purine base derivatives and pyrimidine base derivatives, which are synthesized entirely in one machine, can also be used. Furthermore, those that are already commercially available can also be used.

In addition, in the present invention, 23 represented by the formula [Hr]
4-trideoxyglucobylanose can be easily derived and synthesized from ethyl 2-oxocyclopentanecarboxylate, which is inexpensive and easily available.

[For production]

The anti-inflammatory action of the 2', 3', 4'-)lysoxygluconucleosides (hereinafter abbreviated as 36GN) of the present invention will be explained below.

The anti-inflammatory action of the 2',3',4'-trideoxygluconucleosides (3tlGN) of the present invention is as follows:
There are mainly two points.

First, the axis of 3dGN has a glucose structure, and this structure resembles a hose, so viral enzymes (kinases, deaminase, etc.) take in 3dGN, mistaking it for a DNA structure. . As a result, 3dGN exerts an antiviral effect by antagonizing viral enzymes and delaying the synthesis of viral DNA.

The second point is that 3dGN has a structure with only one hydroxyl group at the 6' position, so once it is incorporated into viral DNA, it cannot bind to the next nucleoside. That is, 3dGN directly inhibits virus replication as a chain terminator of virus 1)NA.

Existing antiviral agents such as AZT and ACV exhibit antiviral effects through similar actions, but the 3dGN of the present invention has a different action from existing antiviral agents due to the following rationale. There is.

That is, since 3tlG N has 2', 3', 4'-h lysooxyglucose having a flexible cyclic structure in the sugar moiety, it can exhibit a wide antiviral spectrum.

For example, in the case of AZT, the sugar moiety is ribose, a relatively rigid five-membered ring, so the distance between the base moiety and the hydroxyl group of the bran is constant, and it follows the viral enzyme, which changes as the type of virus changes. Can not. This results in a relatively narrow anti-56 virus spectrum. However, the 3dGN of the present invention
Because it has a relatively flexible six-membered ring glucose skeleton in its sugar moiety, it can better respond to changes in viral enzymes and has a broader antiviral spectrum.

Furthermore, ACV will be explained as a comparison. ACV has an acyclic structure in its sugar moiety, and the distance between the hydroxyl group of the sugar and the base is relatively high. However, since it has an acyclic structure, in addition to the rotation around the carbon next to the hydroxyl group, there is also rotation around the 2nd and 11th carbons counting from the hydroxyl group, making the relationship between the base and the hydroxyl group too complicated. There is. In other words, ACV has a base part and a hydroxyl group (like the nucleic acids (such as thymidine) that make up DNA).
Unfortunately, the direction of the carbon atoms with =1 does not always face the same direction, which limits the number of virus enzymes that can interact with them.

However, although the 3dGN of the present invention is relatively flexible, it does not have an acyclic structure, so the direction of the base and hydroxyl group is determined by the direction of the nucleic acid (for example, demidine) that makes up the DNA.
We were able to realize a structure similar to that of

As mentioned above, the 3dGN of the present invention has a special partial structure of 2', 3', and 4'-trideoxyglucose in its molecule, so it is more effective than conventional antiviral agents. It is a new antiviral agent with a broad antiviral spectrum.

The antiviral agent of the present invention, 2', 3'', 4'-)lysoxygluconucleosides (3dGN), has a broad antiviral spectrum, but retroviruses
especially AIDS virus) and herper virus (especially H
SV-1, HS V-2, etc.), it exhibits particularly high antiviral activity.

Furthermore, the antiviral agent of the present invention, 2',3',1-
1-lysoxygluconucleosides (3dGN) are
All of them are good antiviral agents, but among them, the compounds shown below show high antiviral performance.

In other words, the compound is a) 6-aminopurine-9 2.3',4'-1-lysooxyglucopyranoside.

b) 6-Hydroxybulin-9 2', 3', 4'-J-lysooxyglucopyranoside.

C) Purine-9 2',3',,4' l-lysooxyglucopyranoside dl 2-amino-G-hydroxypurine-92'
,3',,4'-1-lysooxyglucopyranoside.

e) 6-Fluoropurine-9 2',3',,4'-1-lysooxyglucopyranoside.

1) 6-chloropurine-9 2',3',,4'-1-lysooxyglucopyranoside.

g) 2-amino-6-fluoropurine-92', 3.4
'i Lysooxyglucopyranoside.

h) 2-amino-6-chloropurine-9-2',3
',,4'-1-lysooxyglucopyranoside.

i) i(2,3,4-trideoxyglucopyranosyl)-uracil i) I-(2,3,4-trideoxyglucopyranosyl)-thymine, k) I-(2,3,4 -) lysoxyglucopyranosyl)-cytosine.

) 1-(2,11,4-trideoxyglucopyranosyl) 5-bromo-uracil, m)l-(2J, 4-trideoxyglucopyranosyl) 5-fluorouracil, and the like.

The 2.3.4-1-lysoxyglucobylanose derivative related to the present invention can be synthesized using ethyl 2-oxopentanecarboxylate as a raw material, which is inexpensive and available manually. As an example,
A method for synthesizing 1-acetyl-6-hendiyl 234-1-lysooxyglucose is shown (Scheme i).

9 0 elhylen glycol H” / benz
ene; b) LAII /ε120++'
/acetone; di m-CPU
8/Cl-1cI]; e) f
ix:+0/Py;disiamylbo+ane/
THF; g) ＾ct O/PyTMS
Cl, 1m1da+ole/C1l, Ch;
tl DIB^1. / 161uene ;^
c+ o/i:tt N i.e. ethyl 2-oxopentanecarboxylate (1)
After protecting the ketone moiety as a ketal, the ester moiety is reduced with a metal reagent and further deprotected to obtain 2-hydroxymethyl-pentanone (2).

Further oxidation of compound 2 provides the corresponding lactone, 5-hydroxymethyl-δ-pentanolactone (3). By protecting the alcohol moiety of compound 3 as benzoate, selectively reducing the lactone moiety to form hemiacetal, and then converting it to acetate, the desired 1-acetyl-6-penzoyl-2.34-1-lysooxy Glucose (4) can be synthesized.

Furthermore, when the alcohol moiety of compound 3 is converted into tert-butyldimethylsilyl ether, the lactone moiety is reduced to form hemiacetal, and further acetate is obtained.
-acetyl-6-tert-butyldimethylsilyl-2
, 3, Il) Lysoxyglucose (5) can be synthesized.

(Scheme 1.) 2 The synthesized 2.3.4-1-lysoxyglucopyranocose derivative as described above and the nucleobase 2 synthesized from cheap RNA, or the chemical synthesis of them. The 2', 3', 4' trideoxygluconucleoside (36GN) related to the present invention can be easily combined with a nucleobase derivative obtained by modification.

For example, 1-acetyl-6-tert-butyldimethylsilyl-2,34-1-lysooxyglucose and ditrimethylsilylcytosine derived from cytosine are reacted in a methylene chloride solvent using ethylaluminum dichloride as a Lewis acid. After coupling, by deprotecting the tert-butyldimethylsilyl group, 1-(2,3,4-trideoxyglucopyranosyl)
-Cytosine is obtained.

To further illustrate, 1-acedel-6-penzoyl-2
341 Lysoxyglucose is reacted with trimethylsilyl bromide to produce 1-bromo-6penzoyl~12.
After producing 3.4-tetradeoxyglucose, coupling occurs when this is reacted with 6-chloropurine activated by sodium hydroxide, and further deprotection of the benzoate produces 6-chloropurine-9-2. ,3
, 4 trideoxyglucopyranoside is obtained.

As described above, according to the synthesis method of the present invention, the antiviral agent related to the present invention can be synthesized using a simple method from inexpensive raw materials.

〔Example〕

The present invention will be explained in more detail below with reference to Examples.

However, the following examples are shown for illustrative purposes only, and are not intended to limit the scope of the present invention in any way.

(1) Synthesis of Production Example The synthesis of the present compound is carried out using ethyl 2-oxocyclopencunecarboxylate as a mediating substance and the methods (1) to (yii) shown below. , together.

(1) Ethyl 2-oxocyclopentanecarboxylate 46
．． 8 g (3(1 (1 mmol), ethyl glycol 93.1 g (1.5 mol), para)-luenesulfonic acid 5.17 g (30 mn+ol) was mixed with benzene 1.
The mixture was placed in an eggplant flask containing No. 51 and refluxed to react. The reaction was continued while removing water produced from the reaction system, and the mixture was refluxed for 20 hours. After the reaction was completed, the solvent was distilled off using a rotary evaporator, and the residue was dissolved in ethyl acetate and washed twice each with a saturated aqueous solution of sodium bicarbonate and saturated brine.

After drying the organic layer over anhydrous thorium sulfate, the solvent was distilled off to obtain 57.6 g (288 mmol) of ethyl 2.2-ethylenedioxycyclobentanecarboxylate (9
6%).

(11) To 400 ml of distilled and dried anhydrous THF (tetrahydrofuran), add 1.4 g (300 ml) of LAH (lithium aluminum hydride) I
mmo I) under a nitrogen atmosphere to reduce the L of THF.
A H suspension was prepared and cooled to -20°C while stirring with a stirrer. To this L A H suspension, (1
), 50 g (250 mmol) of ethyl 2,2-ethylenedioxycyclobentanecarboxylate,
A solution of 200III THF was slowly added dropwise in a nitrogen atmosphere F to cause a reaction. After the dropwise addition was completed, stirring was continued for 1 hour. After 1 hour, saturated ammonium chloride was added little by little to stop the reaction. The mixture was stirred for a while, and when bubbles stopped appearing, ether and anhydrous sodium sulfate were added to dehydrate and extract. After filtering the ether layer to remove solids, the solvent was distilled off using a rotary evaporator, and the resulting residue was redissolved in ether. This ether solution was dried with anhydrous thorium sulfate, passed through a short silica gel column, and then the solvent was distilled off using a rotary evaporator. The resulting residue was distilled (bp 150-160°C/18mmHg
) 31.6 g (200 mmol) of 1,1-ethylenedioxy-2-hydroxymethylcyclopropane
(80%).

(iii) 1.1-ethylenedioxy-2-hydroxymethylcyclopropane 30.0 g (190 m
After dissolving mo 11 in 250 m of acetone, add a few drops of water and 0.344 g of para-toluenesulfonic acid (2
mmol) and stirred with a stargie at room temperature. Five minutes after starting the reaction, a saturated aqueous solution of sodium bicarbonate was added to stop the reaction, and after stirring for a while, ethyl ether and sodium hydrosulfate were added and stirred.
Extracted. The ether layer from which the solid content was removed by filtration was concentrated using a rotary evaporator, and the residue was distilled to obtain 2-hydroxymethyldicyclopropanone 2.
1.0 g (184 mmol) was obtained (97%).

(iv) 20.0 g of 2-hydroxymethylcyclopropane in 1.51 g of anhydrous chloroform (175
mmol) and mCPBA while stirring at room temperature.
(Metachloroperbenzoic acid) 36.2g (210m
mol) and 7.64 g (2
10 mmol) was added little by little at the same time. After the addition of mCPBA was completed, the mixture was allowed to react at room temperature for 5 hours with stirring. After 5 hours, the reaction solution was directly filtered to remove the solid content, and the filtrate was concentrated using a rotary evaporator. The residue was developed on a silica gel column chromatography using a mobile solvent of ether and methanol. It was fractionated. Rf value is 0.47 (ether/methanol-371)
The fractions were collected and concentrated to obtain 5-hydroxymethyl-δ-pentanolactone (16.14 g f124 mmol) (71%).

Colorless and transparent h11 shape Boiling point 120°C (0.5n+mH
g) NMR spectrum CClIC13) ・δ1.2
~2.2 (4H, m, C3and C4-H)2
．． 2-2.75 (2H, m, C2-H) 3.25
(IH, s, disappeared by addition of C6-0HD20) 3.55 (2H, dd, C6-H) C1~4.1
(IH, m, C5-H) MS spectrum (F to B
-MS; m/z)M + i, 1.
31 Rf value (5ilica Get HF254) ;0
, 41 (C20/hleol+ ・3/I) 7 8 (v) 5-hydroxymethyl-δ-pentanolactone 1
5 = Og (]15 mmol), benzoic anhydride 52
．． 03 g (23 [Immol)] and 1.4 g (I 1.5 + nmol) of dimethylaminopyridine were dissolved in 100 ml of anhydrous pyridine I, and the mixture was stirred overnight at room temperature to react. After the reaction was completed, pyridine was distilled off using a rotary evaporator, and the residue was dissolved in ethyl acetate.
Specified aqueous hydrochloric acid solution, saturated aqueous sodium bicarbonate solution.

Each was washed twice with a saturated ammonium chloride aqueous solution. The ethyl acetate layer was dried over anhydrous sodium sulfate and concentrated on a rotary evaporator. The residue was separated and purified by silica gel column chromatography (mobile phase: hexane/ether). Rf value is 0,2
The fractions of (hexane/ether-171) were collected and concentrated to obtain 25.3 g (108 mmol) of 5-benzyloxymethyl-δpentanolactone (94%
).

(Vi) 23.4 g (IQOmmol) of 5-benzyloxymethyl-δ-pentanolactone was dissolved in 200 v+ of anhydrous THF under a nitrogen atmosphere and cooled to 0°C with stirring. To this THF solution, 1.2M dicyamylborane THF solution (G, Zwei)el e
l, 8J, Am, Chem, Soc, 84.190
(1962)) slowly (250 m/ ) L
, reacted. After continuing to stir for one day at room temperature,
Add 3 inches of water and reflux for 30 minutes. After that, the reaction solution was
70 ml of hydrogen peroxide solution was slowly added to the solution while cooling the solution to 'C' while adjusting the pH to 7 to 8 with a 3N aqueous sodium hydroxide solution. After the dropwise addition was completed, the mixture was stirred for a while and brought to room temperature. This solution was concentrated using a rotary evaporator to remove most of the THF, and the solution was separated and extracted with chloroform. The chloroform solution thus obtained was mixed with Jl? After drying with aqueous calcium chloride, it was concentrated to dryness using a rotary evaporator. This residue was separated and purified by silica gel column chromatography (developing solvent: hexane/ether-5/1). R,f
The fractions with a value of 0.3 (hexane/ether 1/i, ) were collected and concentrated to give 18.4 g (78,0
mmol) was obtained (78%).

(vii) 2.3. ←Trideoxyglucose-6-
16.0 g (67.7 mmol) of penzoate, 20.42 g (200 imol) of acetic anhydride, and 185 g (7.0 mmol) of dimethylaminopyridine are dissolved in 200 m4 of anhydrous pyridine and reacted at room temperature for 5 hours. After the reaction, pyridine was distilled off using a rotary evaporator, the residue was dissolved in ethyl acetate, and the liquid was separated twice each with 1N hydrochloric acid aqueous solution, saturated sodium bicarbonate aqueous solution, and saturated ammonium chloride aqueous solution. Washed. The ethyl acetate layer was dried over anhydrous sodium sulfate and then concentrated to dryness using a rotary evaporator. This was separated and purified by silica gel column chromatography (developing solvent: hexane/ether-8/1). R,f
The value is 0.59 (hexane/ether = 1-/i-
) fractions are collected and concentrated to obtain the target compound, 1
-Acetyl-6-penzoyl-234-trideoxyglucose 16.2g (58.2mol) was obtained (8
6%).

Colorless transparent oily NMR spectrum (ClICff 3 ): δ]
2-2.0 (6H,m, C22,1(3H,s,
CL Co )37-4.45 (3H, m,
C55,5~6.3 (IH,m, C57,2~8
．． 2 (5H, m, cl.

MS spectrum (FAII-MS M+1.279 Rf value (5ilica Gel HF254) Q, 5
9 (hexame / EI20 ・I/l)an
d C6-0H) H) +1. , CQ-) ; m/Z) C3and C4-H) Synthesis and production example 1. 1.43 g (5,1
3 mmol) in anhydrous chloroform under nitrogen atmosphere
m7! The mixture was dissolved in water and cooled to 0° C. without stirring. To this chloroform solution, add 0.989 trimethylsilyl bromide.
g (6.5 mmol) I 2 was slowly added dropwise. After the dropwise addition was completed, the temperature was returned to room temperature and stirring was continued for 1 hour.

After 1 hour, it was cooled again to -20°C.

After confirming that the temperature inside the reaction system was 120°C, 6-chloro-9-trimethylsilylpurine derived from 6chloropurine [6-chloropurine and N,O
-obtained by mixing and reacting bis-(trimethylsilyl)-acetamide and then removing the solvent] 0.7
93g (5.13mmol) in chloroform solution 10ml
# was slowly added dropwise to react. After dropping F, slowly raise the temperature to room temperature while continuing to stir, and at room temperature,
Stirring was continued for 1-hour. After 1 hour, the reaction was stopped by blowing into ice water and extracted with chloroform. The chloroform layer was washed successively with a 0.5N aqueous hydrochloric acid solution, a saturated aqueous solution of sodium bicarbonate, and a saturated aqueous solution of ammonium chloride, and the chloroform layer was dried over sodium sulfate and then concentrated using a rotary evaporator. The obtained oily substance was subjected to silica gel column chromatography (hexane/
The fractions with an Rf value of 0.4 (ether only) were collected and concentrated, and this was vacuum dried (50°C, 1 hour) to obtain 6-chloropurine-115).
9-2'3',4'-trideoxyglucopyranoside-6'-benzoate 1.20 g (3', 21m
mol) as a glass (63%).

6-chloropurine-9-2' thus obtained,
3'.

4′-trideoxyglucopyranoside-6′-benzony 1□ 1.00 g (2.68 mmol) was dissolved in ammonia-4 raw methanol (ammonia 20%),
The reaction was carried out at 0°C for 5 hours. After the reaction was completed, ammonia was distilled off at 10°C, and then methanol was distilled off using a rotary evaporator. The residue was purified by silica gel column chromatography (chloroform/methanol-9/
1), the fractions with an Rf value of 0.76 were collected and concentrated, and the
-2',3',,4'-)lysoxyglucopyranoside 0.583 g (2.17 mmol) was obtained (8
1%).

Colorless transparent granular crystals Melting point 126°C NMR spectrum (D!tlsM6) δ1.3-
2.3 (6H, m, C2'C3' an
dC4'-H) 3,1-3.9 (3I-(,m, C5'and
C6'-I4) 4.6-4.9 (IH, t+
Disappeared by addition of C6'-0H020) 56-6.0 (IH, dd, CI'-H) 8.4
(1 knife (, s, C8-H) 11.7 (IH
, s, C2-H) MS spectrum (FAB-IJS
; m/+) M 1, 269 R, f value (5ilica Get HF254);
0,76 (C11l4/MeOH=9/l) Production Example 3.6-Amitpurine-9-2', 3', 4
Synthesis and production example 2 of trideoxyglucopyranoside (3). 1.10 g (2,9
5 mmol) was dissolved in ammoniacal methanol (20% ammonia) and reacted in a sealed tube at 60° C. for 10 hours. After the reaction was completed, ammonia was distilled off at 10°C, and then methanol was distilled off using a rotary evaporator. The residue was separated and purified by silica gel column chromatography (chloroform/methanol-9/1), and fractions with an Rf value of 0.31 were collected and concentrated to obtain the Fj-like compound 6-amitpurine-9-2', 3′,, l
-) Lysoxyglucopyranoside 0.676 g I2
．． 17 mmol) was obtained (92%).

White nail-shaped crystals Melting point: 192°C NMR spectrum (DMSO-δ6): δ1.3-2
．． 4 (6H, m, C2', C3' and C
4"H) 3.2~4.0 (3H, m, C5'and C6
'-H)4.5~4 g(If(,t, Cfi"O
Disappeared by adding HD and O) 5.55 to 5.9 (IH, dd, CI'-H) 7
．． 25 (IH,s, NH2)8.2 (IH
,s, C8-H)fl,4 (IH,s, C
2-H) MS spectrum (FAB-MS; m/+
)5 6 M+1. 250 R, f value (5ilica Gel HF254) D,
3] (CHC(l q / MeOtl ・9/
j) (2) Antiviral test Antiviral data of representative compounds according to the present invention are shown below. The compound number indicates the number of the above-mentioned example illustrating the preparation method in the Examples of the present invention.

Test Example 1 The antiviral activity of the compounds represented by the general formulas [I] and [71] of the present invention was determined by the test method of Rowe et al. (+, W
, Violog L4211afi (1970)). Table 1 shows the antiviral results of representative compounds.
It was shown to.

Virus: Moloney-mutine (euk
emia vi+ui cells: 5C-1 Table 1-1 Representative 2', 3', 4'-)lysoxygluconucleosides with anti-MuLV activity Compound number Abbreviation ED50 (μm) 2 d
ddg-6CI-P u 5-103
dddg-Ad 15 Test Example 2゜The antiviral activity of the compounds represented by the general formulas [I] and [rT] of the present invention was demonstrated by
It was tested using

Primary culture cells (Chick EmbBo Fib+ol
asl) for approximately 30 minutes. Then, stepwise diluted samples were added, and after 4 to 7 days, R8
The stage at which cell transformation due to V infection was inhibited was determined by microscopy. The results are shown in Table 2.

Table 21 Representative 2', 3', 4'-trideoxygluconucleosides with anti-RSV active compound number Abbreviation Concentration (/l/m4) dddg C 14 32-64 3 dddg-A, d 64
~125 As shown in Tables 1 and 2, the compounds of the present invention exhibit excellent antiviral effects and have a broad antiviral spectrum, so they can be used as therapeutic agents for viral diseases such as AIDS and herpes. It is clear that this is effective.

〔Effect of the invention〕

As explained above, according to the present invention, a novel compound with excellent antiviral activity is provided. For example, it is extremely effective as a therapeutic agent for viral diseases such as AIDS and herpes.

9

Claims (16)

[Claims] (1) General formula [I] ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R_1 is a hydrogen atom, hydroxyl group, amino group, alkyl group, halogen atom, alkoxy group, or mercapto group, and R_2 , R_3 are each a hydrogen atom or an amino group). (2) 6-aminopurine-9-2',3',4'-trideoxyglucopyranoside, 6
-Hydroxypurine-9- 2',3',4'-trideoxyglucopyranoside, Purine-9- 2',3',4'-trideoxyglucopyranoside, 2
-amino-6-hydroxypurine-9-2',3',4'-trideoxyglucopyranoside, 6
-fluoropurine-9- 2',3',4'-trideoxyglucopyranoside, -
Chloropurine-9-2',3',4'-trideoxyglucopyranoside, 2
-amino-6-fluoropurine-9-2',3',4'-trideoxyglucopyranoside, 2
-amino-6-chloropurine-9-2',3',4'-trideoxyglucopyranoside. (3) General formula [II] ▲There are mathematical formulas, chemical formulas, tables, etc.▼[II] (In the formula, X is a hydroxyl group or an amino group, and Y is a hydrogen atom, an alkyl group, or a halogen atom.) Represented by Compound. (4) 1-(2,3,4-trideoxyglucopyranosyl)-uracil, 1-(2,3,4-trideoxyglucopyranosyl)-
Thymine, 1-(2,3,4-trideoxyglucopyranosyl)-
Cytosine, 1-(2,3,4-trideoxyglucopyranosyl)-
5-bromouracil, 1-(2,3,4-trideoxyglucopyranosyl)-
4. The compound according to claim 3, selected from 5-fluorouracil. (5) General formula [III] ▲ Numerical formulas, chemical formulas, tables, etc. are available ▼ [III] (In the formula, Ra is a hydrogen atom or a protective group for alcohol selected from acetyl group, benzoyl group, and esters having up to C10 carbon atoms) Or benzyl group, tetrahydropyranyl group, ethoxyethyl ether group, trityl group, t-
A compound represented by the following formula (representing either a butyldimethylsilyl group or an alcohol protecting group selected from ethers having up to C20 carbon atoms, and Rb represents a hydrogen atom or an acetyl group). (6) 1-acetyl-6-benzoyl-2,3,4-trideoxyglucose, 1-acetyl-6-(t-butyldimethylsilyl)-2
, 3,4-trideoxyglucose. (7) General formula [IV] ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [IV] (In the formula, R_1 is a hydrogen atom, a hydroxyl group, an amino group, an alkyl group, a halogen atom, an alkoxy group, or a mercapto group. (R_2 and R_3 are each a hydrogen atom or an amino group) and the general formula [III] ▲There are mathematical formulas, chemical formulas, tables, etc.▼[III] (In the formula, Ra is a hydrogen atom or , an acetyl group, a benzoyl group, and an alcohol protecting group selected from esters having up to C10, or a benzyl group, a tetrahydropyranyl group, an ethoxyethyl ether group, a trityl group, a t-
(Hereinafter, this will be referred to as 2, 3, A compound represented by the general formula [I] (hereinafter referred to as 2', 3' , 4'-trideoxyglucoprine nucleosides). ▲There are mathematical formulas, chemical formulas, tables, etc.▼〔I〕 (R_1, R_2, R_3 in the formula are the same as the general formula [IV]) (8) General formula [V] ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [V] (In the formula, X is a hydroxyl group or an amino group, and Y is a hydrogen atom, an alkyl group, or a halogen atom) Represented by Pyrimidine compounds and general formula [III] ▲Mathematical formulas, chemical formulas, tables, etc.▼[III] (In the formula, Ra is a hydrogen atom or protection of an alcohol selected from acetyl group, benzoyl group, and esters having up to C10 carbon atoms) or a protecting group for an alcohol selected from a benzyl group, a tetrahydropyranyl group, an ethoxyethyl ether group, a trityl group, a t-butyldimethylsilyl group, and an ether having a carbon number of up to C20,
Rb represents a hydrogen atom or an acetyl group) (2,3,4-trideoxyglucopyranose derivative) using an appropriate coupling reagent, and then Ra is deprotected. A method for producing a compound represented by the general formula [II] (hereinafter referred to as 2',3',4'-trideoxyglucopyrimidine nucleosides). ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [II] (X and Y in the formula are the same as the general formula [V]) (9) General formula [I] and general formula [II] characterized in that sodium hydride and trimethylsilyl bromide are used as the coupling reagent according to claims 7 and 8.
(hereinafter, this will be referred to as 2', 3', 4')
- a method for producing trideoxygluconucleosides). (10) A silylation agent such as trimethylsilyl chloride, N,O-bis-(trimethylsilyl)-acetamide, and trimethylsilyl bromide are used as the coupling reagent according to claims 7 and 8. ,3
A method for producing ',4'-trideoxygluconucleosides. (11) A method for producing 2',3',4'-trideoxygluconucleosides, which comprises using a Lewis acid such as ethylaluminum dichloride as the coupling reagent according to claims 6 and 7. (12) 2', 3', 4 represented by general formula [I] according to claim 1 and/or general formula [II] according to claim 3
An antiviral agent containing at least one type of ′-trideoxygluconucleosides as an active ingredient. (13) 2', 3', 4 represented by general formula [I] according to claim 1 and/or general formula [II] according to claim 3
An antiretroviral agent containing at least one type of ′-trideoxygluconucleosides as an active ingredient. (14) 2', 3', 4 represented by general formula [I] according to claim 1 and/or general formula [II] according to claim 3
An anti-herpes agent containing at least one type of ′-trideoxygluconucleosides as an active ingredient. (15) 2', 3', 4 represented by general formula [I] according to claim 1 and/or general formula [II] according to claim 3
An anti-AIDS virus agent containing at least one type of ′-trideoxygluconucleosides as an active ingredient. (16) 2', 3', 4 represented by general formula [I] according to claim 1 and/or general formula [II] according to claim 3
Experimental drugs and experimental reagents used in genetic engineering, which contain at least one type of ′-trideoxygluconucleosides as an active ingredient.