JPS6055076B2 - Nitrosourea derivatives and their production method - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to novel nitrosourea compounds and methods for their production.

More specifically, a phenyl group having 1 to 3 substituents selected from the group consisting of a general formula kyl group, a lower alkoxy group having 1 to 4 carbon atoms, a hydroxyl group, and a nitro group; or an oxiranyl group, a tetrahydrofuryl group, a 1,3 - represents a heteromonocyclic group selected from the group consisting of a dioxolanyl group, a 1,4-dioxanyl group, a morpholino group, a tetrahydro S,S-dioxothienyl group, a furyl group, a thienyl group, and a pyridyl group, and R2 is an aldopent group; Represents a pyranosyl group, an aldohexopyranosyl group, or an O-aldohexopyranosyl (1→4)-aldohexopyranosyl group, and A is a single bond or a straight or branched chain having 1 to 3 carbon atoms. (representing an alkylene group).

It is known that (N-chloroethyl-N-nitrosocarbamoyl)-amino derivatives of monosaccharides can be obtained by nitrosating (N-chloroethylcarbamoyl)amino monosaccharides with alkali metal nitrite salts such as sodium nitrite. (JP-A No. 51-108043, JP-A-51-26
No. 876, JP-A No. 51-52128), these publications disclose 1-(2-chloroethyl)-1-nitroso-3-(D-mannopyranosyl)urea and 1-(2-
chloroethyl)-1-nitroso-3-(D-glucopyranosyl)urea (hereinafter abbreviated as ゜゜GANU゛).

) has been shown to have a survival effect on mice intraperitoneally transplanted with lymphocytic leukemia cells. Furthermore, 1-(2-chloroethyl)-1-nitroso-3-(D-
lactosyl)urea and 1-(2-chloroethyl)-
It is also known that 1-nitroso-3-(D-maltosyl)urea can be synthesized from the (N''-chloroethylcarbamoyl) amino form of the corresponding disaccharide by the same method as above and exhibits anti-leukemia activity. JP-A No. 51-141815) In response, the present inventors have conducted various studies and found that the novel nitrosourea compound [1] exhibits strong anti-cancer and anti-leukemic effects. For example, in leukemia. L-1
When each compound was continuously administered intraperitoneally for 5 days to mice transplanted with 2W cells, 1-(2chloroethyl)-1-nitroso-3-(thiophen-2-ylmethyl)-3-(L-arabino pyranosyl) urea is 0.3519/K9, 1-(2-chloroethyl)-1-
Nitroso-3-cyclopropylmethyl-3-(L-arabinopyranosyl)urea is 1.1TfLg/Kg, 1-(
2-chloroethyl)-1-nitroso-3-(oxiran-2-yl-methyl)-3-(L-arabinopyranosyl)urea is 1.05 m9/K9, 1-(2-chloroethyl)-1-nitroso-3-tetrahydro Furufuriru 3-
(D-galactopyranosyl) urea can increase the average survival days of the mice by 30% compared to the non-administered group at each dose of 1.7m9/K9.

Furthermore, the nitrosourea compound [1] of the present invention has low toxicity and exhibits particularly excellent safety when used as an antitumor agent.

For example, 0ptima1d0 for leukemia L-1210
se (0, D: optimal dose = daily dose showing the maximum survival effect for the mouse)/1. L. S3.

(The daily dose required to increase the average survival days of mice transplanted with tumor cells by 30% compared to the non-administered group), the therapeutic index is calculated from the ratio of 1-(2-chloroethyl) Nitroso-3-(thiophen-2-yl-methyl)-3-(L-arabinopyranosyl)urea, 1-
(2-chloroethyl)-1-nitroso-3-tetrahydrofurfuryl-3-(D-galactopyranosyl)urea,
1-(2-chloroethyl)-1-nitroso-3-(α-
methylbenzyl)-3-[0-α-D-glucopyranosyl(1→4)-D-glucopyranosyl]urea and 1
-(2-chloroethyl)-1 nitroso-3-phenethyl[0-α-D-glucopyranosyl(1→4)-D
-Glucopyranosyl]urea is 7 times to 1 times more than GANU
Shows a therapeutic index that is twice as large. Moreover, compound [1] is M. T
．． D (maximum tolerated dose = 100% inhibition of the growth of Ehrlichi's ascites carcinoma without killing the transplanted mouse)
Maximum inhibiting dose)/M. E. D. Even when the therapeutic index is calculated from the ratio of (minimum effective dose=minimum dose that inhibits the growth of Ehrlichi's ascites carcinoma by 100%), it is characterized by a very large therapeutic index.

For example, 1-(2-chloroethyl)-1-nitroso3
-(thiophen-2-yl-methyl)-3-[0-α-
D-glucopyranosyl(1→4)-D-glucopyranosyl]urea, 1-(2-chloroethyl)-1-nitroso-3-(P-methoxybenzyl)-3-[0-α-D-
Glucopyranosyl(1→4)-D-glucopyranosyl]urea and 1-(2-chloroethyl)11-nitroso3-benzylu3-[0-α-D-glucopyranosyl(1→4)-D- Glucopyranosyl urea is SANU
shows a therapeutic index approximately 8 times greater than

Furthermore, the compound [1] of the present invention has very mild bone marrow toxicity and can be administered continuously, making it possible to serve as an antitumor agent that is superior to known compounds. In the above general formula [1], examples of R1 include alicyclic groups such as cyclopropyl group, cyclobutyl group, cyclopentyl group and cyclohexyl group; phenyl group; or monochlorophenyl group (e.g. P-chlorophenyl group), monomethyl phenyl group (e.g. P-methylphenyl group),
Trimethylphenyl group (e.g. 2,4,6-trimethylphenyl group), monomethoxyphenyl group (e.g. P
-methoxyphenyl group), dimethoxyphenyl group (e.g. 2,3-dimethoxyphenyl group), trimethoxyphenyl group (e.g. 3,4,5-trimethoxyphenyl group), monohydroxyphenyl group (e.g. P- substituted phenyl groups such as hydroxyphenyl group) and mononitrophenyl group (e.g. P-nitrophenyl group); or oxiranyl group, tetrahydrofuryl group (e.g.
tetrahydrofuran-2-yl group), 1,3-dioxolanyl group (e.g. 1,3-dioxolan-2-yl group, 1,3-dioxolan)-4-yl group), 1,4-dioxanyl group (e.g. 1 , 4-dioxan-2-yl group), morpholino group, tetrahydro S,S-dioxothienyl group (e.g., tetrahydro S,S-dioxothiophene-3-yl group), furyl group (e.g.,
(furan-2-yl group), thienyl group (e.g., thiophen-2-yl group), and pyridyl group (e.g., pyridyl-2-yl group); examples of R2 include, for example, D- ribopyranosyl group, L-arabinopyranosyl group, D-arabinopyranosyl group and D
- an aldopentopyranosyl group such as a xylopyranosyl group; xopyranosyl group; e.g. O-
α-D-glucopyranosyl (1→4)-D-glucopyranosyl group (=D-maltosyl group) and O-β-D-
Examples include O-aldohexopyranosyl(1→4)-aldohexopyranosyl groups such as galactopyranosyl(1→4)-D-glucopyranosyl group (=D-lactosyl group).

Furthermore, examples of A include a single bond, a linear or branched alkylene group such as a methylene group, an ethylene group, a propylene group, and a methylmethylene group. Preferred groups of the compound [1] of the present invention include an alicyclic group in which R1 is selected from the group consisting of a cyclopropyl group, a cyclopentyl group, and a cyclohexyl group; phenyl; a monochlorophenyl group, a monomethylphenyl group, a trimethylphenyl group, and a monomethylphenyl group; A substituted phenyl group selected from the group consisting of methoxyphenyl group; or a heteromonocyclic group selected from the group consisting of oxiranyl group, tetrahydrofuryl group, furyl group, and thienyl group, and R2 is D- or L-aldopentopyra nosyl group, D-aldohexopyranosyl group, or O1D-aldohexopyranosyl-(1→4)-D-aldohexopyranosyl group, and A is a single bond or has 1 to 2 carbon atoms. Examples include compounds that are alkylene groups, and other preferred compounds [
Group 1] includes an alicyclic group in which R1 is selected from the group consisting of a cyclopropyl group, a cyclopentyl group, and a cyclohexyl group; a phenyl group: a P-chlorophenyl group;
P-methylphenyl group, . a substituted phenyl group selected from the group consisting of 2,4,6-trimethylphenyl group and P-methoxyphenyl group; or oxirane-2-yl group;
A tetrahydrofuran-2-yl group, a furan-2-yl group, and a thiophen-2-yl group, and R2 is a D,-ribopyranosyl group, an L-arabinopyranosyl group, a D-xylopyranosyl group, a D-glucopyranosyl group, or a D-galactosyl group. Examples include compounds in which the compound is a pyranosyl group or an O-α-D-glucopyranosyl (1→4)-D-glucopyranosyl group, and A is a single bond or an alkylene group having 1 to 2 carbon atoms. , as a more preferable group, R1 is cyclopropyl, cyclohexyl group, phenyl group, P-methylphenyl group, 2,4,6-trimethylphenyl group, P-methoxyphenyl group, oxirane-2
-yl group, is a tetrahydrofuran-2-yl group, a furan-2-yl group, or a thiophen-2-yl group, and R2 is an L-arabinopyranosyl group, a D-galactopyranosyl group, or an O-α -D-glucopyranosyl(1→4)-D-glucopyranosyl group, and compounds in which A is a single bond, a methylene group, an ethylene group, or a methylmethylene group can be mentioned.

According to the present invention, the nitrosourea compound [1] has the formula [■]
It can be produced by nitrosating the compound shown below. (However, R1, R2 and A have the same meanings as above) In addition, a nitrosourea compound in which R1 is an oxiranyl group in formula [1] is represented by the general formula (R2 and A have the same meanings as above). The compound represented by the general formula (wherein R2 and A have the same meanings as above) is obtained by nitrosating the compound, which is then epoxidized.

Raw material [former can be easily produced, for example, formula R1
-A-NH2 or CH2=CH-A-NH2 (however,
A primary amine represented by formula R1 and A have the same meanings as above) and a compound represented by formula R2-0H (wherein R2 has the same meanings as above) are mixed in an inert solvent (e.g. methanol, ethanol). ) at 20°C to 80°C to form the formula〉NH or
> A secondary amine represented by NH n9n2 (where Rl, R2 and A have the same meanings as above) is obtained, and then this secondary amine is mixed with 2-chloroethyl isocyanate and a suitable solvent (e.g., tetrahydrofuran). , methanol, ethanol)
It can be produced by condensation at 00C to 3C)0C.

The nitrosation reaction of the present invention is a compound [formerly or [■″]
can be carried out by contacting with nitrous acid, nitrogen trioxide or nitrogen tetroxide in a suitable solvent.

The reaction is -2 (generation) to 2CFC1 especially -10'C to 0
Preferably, it is carried out at .degree. Inert solvents include water, lower alkanols (e.g. methanol, ethanol),
Tetrahydrofuran, methylene chloride, ethyl acetate,
Acetic acid, formic acid, etc. can be used as appropriate. Nitrous acid is an alkali metal salt of nitrite (e.g., sodium nitrite, potassium nitrite) or a lower alkyl ester of nitrite (
For example, it is obtained by reacting butyl nitrite, amyl nitrite) with an inorganic or organic acid (eg, hydrochloric acid, sulfuric acid, formic acid, acetic acid, etc.), and is preferably used in the nitrosation reaction immediately after preparation. In addition, when using nitrogen trioxide or nitrogen tetroxide, the raw material [■] or [■″]
The reaction is preferably carried out by dissolving or suspending the compound in a suitable inert solvent and passing nitrogen trioxide or nitrogen tetroxide in the presence or absence of a deoxidizing agent. As the deoxidizing agent, sodium bicarbonate, sodium carbonate, potassium carbonate, sodium acetate, potassium acetate, etc. can be used as appropriate. After the nitrosation reaction is completed, the compound of the present invention [1
] or [■] can be easily recovered from the reaction solution, and if necessary, can be further purified by silica gel chromatography.

Epoxidation can also be carried out by treating the compound [■] with an oxidizing agent such as meta-chloroperbenzoic acid in a suitable solvent, and the reaction is carried out between -10'C and 50°C1, especially when 10 is C Proceeds suitably at ~30°C.

As the solvent, methylene chloride, chloroform, benzene, acetic acid, etc. can be used as appropriate. After the epoxidation reaction is completed, the compound [1] of the present invention (R1 = oxiranyl group) can be easily recovered from the reaction solution,
If necessary, it can be further purified by silica gel chromatography. The nitrosourea compound [1] thus obtained is
Ehrlichgan, Sarcoma 180, Leukemia L-12
It exerts a strong antitumor effect against various tumor cells such as 10S Lewis lung cancer, Yoshida sarcoma, and rat ascites liver cancer, prolongs the survival period of warm-blooded animals affected by these tumors, and/or It can suppress the proliferation of tumor cells in blood animals.

Furthermore, the compounds of the present invention can be used for the treatment of malignant lymphoma, leukemia, gastric cancer, liver cancer, and other malignant tumors. When the nitrosourea compound [1] is used for pharmaceutical purposes, it may be used in any dosage form suitable for oral or parenteral administration, and it may also be mixed with excipients.

The excipient must not chemically react with the compound [1], and suitable excipients include gelatin, lactose, glucose, salt, starch, magnesium stearate, talc, vegetable oil, and others. Mention may be made of pharmaceutical excipients. The formulation may be a solid formulation such as a tablet, pill, or capsule, or a liquid formulation such as a solution, suspension, or emulsion. Furthermore, when administered parenterally, it can also be used as an injection or suppository. The formulation may also be sterilized and/or contain adjuvants such as preservatives and stabilizers. The pharmaceutical dosage of compound [1] varies depending on the administration method, the age, weight, condition of the patient, and the disease to be treated, but the preferred daily dosage is usually about 0.1 to about 30 mg/Kg. , especially about 0
．． 2 to about 10 m9/Kg. Experimental Examples The therapeutic effects of the nitrosourea compounds of the present invention were tested using the following compounds and methods using mice transplanted with various cancer cells.

Experimental method (4) Effect of suppressing the growth of Ehrlichi's ascites carcinoma in female mice (
A group of 5 ICR mice (body weight: 19-23') was injected with Ehrlitsu ascites cancer cells (1 x 1 Cf').
is implanted intraperitoneally.

Dissolve each test compound in physiological saline (however, CCNU is 0
．． 1% (suspended in Nitsukor HCO-60), which was intraperitoneally administered to mice once a day for 5 consecutive days 2 days after transplantation. The effect was determined by measuring the amount of ascites cancer 7 days after the first administration. (B) Leukemia L-12
Effect of prolonging survival of W cell-transplanted mice in male mice (BDF
A group of 4 mice (weight: 19 to 23 y) was made, and leukemia L-121 Kokushu cells (1 x 1 (P mice)) were intraperitoneally transplanted to these mice.

Each test compound was dissolved in physiological saline, and this was added to the
After a period of time, the drug is intraperitoneally administered to mice once a day for 5 consecutive days. Efficacy was determined by comparing the average survival days between the administered and non-administered groups. Test compound Compound No. Compound name 11-(2-chloroethyl)-1-nitroso-3-benzyl-3-[0-α-D-glucopyranosyl(1→4
)-D-glucopyranosyl]urea
;21-(2-chloroethyl)-
1-Nitroso 3-(P-methylbenzyl)-3-[0
-α-D-glucopyranosyl(1→4)-D-glucopyranosyl]urea31-(2-chloroethyl)-1-nitroso23-(P-methoxybenzyl)-3-[0-
α-D-glucopyranosyl(1→4)-D-glucopyranosyl]urea41-(2-chloroethyl)-1-nitroso3-phenethyl-3-[0-α-D-glucopy3
Lanosyl-(1→4)-D-glucopyranosyl]urea 5
1-(2-chloroethyl)-1-nitroso-3-(α-
methylbenzyl)-3-[0-α-D-glucopyranosyl(1→4)-D-glucopyranosyl]urea 61-
(2-chloroethyl)-1-nitroso-3-furfuryl-3-[0-α-D-glucopyranosyl(1→4)-
D-glucopyranosyl]urea 71-(2-chloroethyl)-1-nitroso-3-[thiophen-2-ylmethyl)-3-[0-α-D-glucopyranosyl(1→4
)-D-glucopyranosyl]urea81-(2-chloroethyl)-1-nitroso3-cyclopropylmethyl-3
-(D-galactopyranosyl)urea 91-(2-chloroethyl)-1-nitroso-3-tetrahydrofurfuryl-3-(D-galactopyranosyl)urea 101-(2-
chloroethyl)-1-nitroso-3-cyclopropylmethyl-3-(L-arabinopyranosyl)urea 111-(
2-chloroethyl)-1-nitroso-3-benzyl-3
-(L-arabinopyranosyl)urea 21-(2-chloroethyl)-1-nitroso-3-(oxiran-2-yl-methyl)-3-(L-arabinopyranosyl)urea 31
-(2-chloroethyl)-1-nitroso-3-(thiophen-2-yl-methyl)-3-(L-arabinopyranosyl)urea 41-(2-chloroethyl)-1-nitroso-3-furfuryl-3-(D- CNUL-(2-chloroethyl)-1-nitro-3-cyclohexylurea;, ANUl-(2-chloroethyl)-1-nitro-3-(D-glucopyranosyl)urea, respectively. Example 1 (shown in Tables 1 and 2)
1) A mixture of 7.2y of D-maltose monohydrate, 2.4y of cyclopropylmethylamine and 20ml of methanol is heated and stirred at a temperature of 60°C for 1 hour.

After the reaction, the reaction solution is concentrated to dryness under reduced pressure, and the resulting residue is washed with ether. [0-α-D-glucopyranosyl(1→4)-D-glucopyranosyl]-cyclopropylmethylamine (i.e., 1-cyclopropylmethylamino-1-deoxy-D-maltose) 7.8f as crude product obtain. Add 7.8y of this crude product to 50% methanol.
A solution of 2.5y of 2-chloroethyl isocyanate dissolved in 10ml of tetrahydrofuran is added thereto at 0°C to 5°C. Stir at room temperature for 1 hour, concentrate the reaction solution under reduced pressure, and add a mixture of ethyl acetate and ether to the resulting residue. 1-(2-chloroethyl)-3
-cyclopropylmethyl-3-[0-α-D-glucopyranosyl(1→4)-D-glucopyranosyl]urea (
That is, 6.8y of 1-(2-chloroethyl)-3-cyclopropylmethyl-3-(D-maltosyl)urea) is obtained as a colorless amorphous powder.

IRv:? 01(c!n-1):335011640,
1535, 1070, 1030NMR (D2O) δ:
0.30-0.70(M,4H,(2)1-(2-chloroethyl)-3-cyclopropylmethyl-3-[0-α
-D-glucopyranosyl(1→4)-D-glucopyranosyl 5.0y of urea and 150ml of tetrahydrofuran
and 20ml of acetic acid, and 20y of anhydrous sodium acetate is added to this.

Add 8 y of nitrogen tetroxide gas to this mixture while stirring on ice.
Communicate through conflict. Stir for another 2 minutes at the same temperature. After the reaction, 200 ml of n-hexane was added and insoluble matter was filtered off. The filtrate is concentrated, the solvent is distilled off, 200 ml of a mixture of ethernimethanol (20:1) is added to the residue, and the precipitated oil is separated. The oil was purified by silica gel chromatography (solvent: ethyl acetate-chloroform-methanol (2:1:1)). 1-(2-chloroethyl)-1-nitroso-3-cyclopropylmethyl-3-[0-α-D-glucopyranosyl(1→4)-D-glucopyranosyl]urea (i.e., 1-(2-chloroethyl) )-1-nitroso-3-cyclopropylmethyl-3-(D-maltosyl)
3.8 fI of urea) is obtained as a pale yellow powder. M. P. 5
rc (decomposition) Translation ν = 01 (C7l-Lini 330 to 169 to 108 1030NMR (D2O) δ: 0.30-0.70 (M
, 4H, [α]r+58.5: (C=1.5 methanol) Tsuji Example 21) D-maltose. Monohydrate 7.2y1 cyclohexylmethylamine 4.0y and 2-chloroethyl isocyanate 2.5y were treated in the same manner as in Example 1-(1) to obtain 1-(2-chloroethyl)-3-cyclohexylmethyl- 3-[0-α-D-glucopyranosyl(1→4)-D-glucopyranosyl]urea (i.e.
1-(2-chloroethyl)-3-cyclohexylmethyl-3-(D-maltosyl)urea) 7.2f is obtained as a colorless amorphous powder.

IRv or more spoon 01 (c!Ft-1): 335 to 165 to 1
54 to 1070 NMR (D2O) δ: 0.5-2.2 (
M, cyclohexyl ring proton) 2) 1-(2-
chloroethyl)-3-cyclohexylmethyl-3-[0
-α-D-glucopyranosyl(1→4)-D-glucopyranosyl] 5.4 g of urea and 8 y of nitrogen tetroxide gas were treated in the same manner as in Example 1-(2), and 1-(2-chloroethyl )-1-nitroso-3-cyclohexylmethyl-3-[0-α-D-glucopyranosyl(1→4)-D
-glucopyranosyl]urea (i.e. 1-(2-chloroethyl)-1-nitroso-3-cyclohexylmethyl-3-(D-maltosyl)urea) is obtained as a pale yellow powder.

M.P. Seki ℃ (decomposition) IRv = Snake 01 (Clfl-1): 16901 to 334
108 to 1030NMR (D2O) δ: 0.5-2.2
(M, cyclohexyl ring proton) [α] Tom +5
1.6) (C=1.2, methanol) Example 3 (1) D
- Maltose monohydrate 7.2f 12-Cyclopentylethylamine 3.4f and 2-chloroethyl isocyanate 2.5f were treated in the same manner as in Example 1-(1),
1-(2-chloroethyl)-3-(2-cyclopentylethyl)-3-[0-α-D-glucopyranosyl(1
→4) 7.8y of 1-D-glucopyranosyl]urea (i.e., 1-(2-chloroethyl)-3-(2-cyclopentylethyl)-3-(D-maltosyl)urea) is obtained as a colorless amorphous powder.

More than 1Rp? 01(C7n-1):3350, 1630,
1-in-law 011070, 1040NMR (D2O) δ:
0.7-2.15(M, (2) 1-(2-chloroethyl)-3-(2-cyclopentylethyl)-3-(a)-α-D-glucopyranosyl(1→4)- D-glucopyranosyl]urea 5.4f and nitrogen tetroxide gas 8fI were treated in the same manner as in Example 1-(2) to obtain 1-(2-chloroethyl)-1-nitroso-3-(2-cyclopentylethyl)-3. -[0-α-D-glucopyranosyl(1→
4) -D-glucopyranosyl]urea (i.e. 1-(
2-chloroethyl)-1-nitroso-3-(2-cyclopentylethyl)-3-(D-maltosyl)urea)4.
2y is obtained as a pale yellow powder.

M. P. 63℃ (decomposition) IRp! ? ? 01 (Cffi-Lini 33601169 1050 NMR (D2O) δ: 0.7-2.1 (M, [
α]e+57.8:C (C=1.2, methanol) Example 4 (1) D-maltose monohydrate 7.2V1 Benzylamine 3.2y and 2-chloroethyl isocyanate 3.0y Example 1-Process in the same way as (1), 1-
(2-chloroethyl)-3-benzyl-3-[0-α-
D-glucopyranosyl(1→4)-D-glucopyranosyl]urea (i.e. 1-(2-chloroethyl)-3
-benzy-3-(D-maltosyl)urea) 6.9f is obtained as a colorless amorphous powder.

IRv = Yen 01 (Ajl-Rini 3320, 1640, 1
535, 1080, 1030NMR (D2O) δ:
7.3-7.55 (M, phenyl proton) 2) 1-(
2-chloroethyl)-3-benzyl-3-[0-α-D
-Glucopyranosyl(1→4)-D-glucopyranosyl]urea 5.4f1 and nitrogen tetroxide gas 8y were treated in the same manner as in Example 1-(2), and 1-(2-chloroethyl)-1- Nitroso-3-benzyru-3-[0-α-D-
Glucopyranosyl(1→4)-D-glucopyranosyl]urea (i.e. 1-(2-chloroethyl)-1-nitroso-3-benzy-3-(D-maltosyl)urea)
3.7' is obtained as a pale yellow powder.

M. P. 70°C-74°C (decomposition) IRvF:. Spoon 01 (0-Lini 330 to 169 lμs
to 1030, NMR (D2O) δ: 7.2-7.6 (M
, phenylprone) [α] r + 27.3 δ (C = 1.
Hemethanol) Example 51) D-maltose monohydrate 7.2y. ．． Example 1 P-chlorobenzylamine 4.2y and 2-chloroethyl isocyanate 3.0f
- Treated in the same manner as in (1) to produce 1-(2-chloroethyl)
-3-(P-chlorobenzyl)-3-[0-α-D-glucopyranosyl(1→4)-D-glucopyranosyl]
Urea (i.e. 1-(2-chloroethyl)-3-(P
-chlorobenzyl)-3-(D-maltosyl)urea)6
．． 3f is obtained as a colorless amorphous powder.

IRv 01 (C7F!-1): 3350, 1640
, 1535, 1080, 1030NMR (D2O)
δ: 7.2-7.5 (M, phenylprone) 2) 1-
(2-chloroethyl)-3-(P-chlorobenzyl)-
3-[0-α-D-glucopyranosyl(1→4)-D
-Glucopyranosyl]urea 5.7y and nitrogen tetroxide gas 8y were treated in the same manner as in Example 1-(2), and 1-(2
-chloroethyl)-1-nitroso3-(P-chlorobenzyl)-3-[0-α-D-glucopyranosyl(1
→4)-D-glucopyranosyl]urea (i.e. 1-
4.0y of (2-chloroethyl)-1nitroso-3-(P-chlorobenzyl-3-(D-maltosyl)urea) is obtained as a pale yellow powder.

M. P. 83℃ (decomposition) IRp Yang spoon 01 (G-1): 105 to 33001169
0NMR (D2O) δ: 7.5 (M, phenyl proton) [α] +16.6: (C = 1.2, methanol) Example 6 (1) D-maltose monohydrate 7.2f1P-
Methylbenzylamine 4.1f and 2-chloroethyl isocyanate 3. y was treated in the same manner as in Example 1-(1) to obtain 1-(2-chloroethyl)-3-(P-methylbenzyl)-3-[0-α-D-glucopyranosyl(1
→4)-D-glucopyranosyl]urea (i.e. 1-
(2-chloroethyl)-3-(P-methylbenzyl)-
3-(D-maltosyl)urea) 7.0' is obtained as a colorless amorphous powder.

IRv: Yen 01 (G-1): 3350, 1640, 15
35, 1070, 1030NMR (D2O) δ:2
．． 30(S,3H,7.2O(Q,4H, phenylproton)(2)1-(2-chloroethyl)-3-(P-methylbenzyl)-3-[0-α-D-glucopyranosyl (1→4)-D-glucopyranosyl] 5.5 y of urea and 8 y of nitrogen tetroxide gas were treated in the same manner as in Example 1-(2), and 1-(2-chloroethyl)-1-nitroso 3-(
P-methylbenzine)-3-[0-α-D-glucopyranosyl(1→4)-D-glucopyranosyl]urea (i.e. 1-(2-chloroethyl)-1-nitroso3
-(P-methylbenzyl)-3-(D-maltosyl)urea) 4.0y is obtained as a pale yellow powder.

M. P. 86) C-feather °C (decomposition) IRp:! ! 01 (Cm-1): 335 to 169 to 10
7 to 1020 NMR (4-DMSO) δ: 2.25 (S
,3H,. l5 (Q, 4H, phenyl proton) [α]
r+29.5f (C=1.2, methanol) Example 7;
) D-maltose monohydrate 7.2y1 (2,4,6-
A mixture of 4.5 y of trimethylbenzyl)amine and 20 ml of methanol is heated and stirred at a temperature of 60° C. for 1 hour.

After the reaction, the reaction solution is concentrated to dryness under reduced pressure, and the resulting residue is washed with ether. 1-[(2,4,6-trimethylbenzyl)amino]-1-deoxy-D-maltose 9
．． 5f is obtained as crude product.

9.5f of this crude product was dissolved in 50ml of methanol, and a solution of 2.5y of 2-chloroethyl isocyanate dissolved in 10mL of tetrahydrofuran was added at 0°C to 5°C.
1. Add at room temperature. Stir for a while. The reaction solution was concentrated under reduced pressure, and the residue was purified by silica gel chromatography (solution: ethyl acetate-chloroform-methanol (1:1:1)).
1-(2-chloroethyl)-3-(2,4,6-trimethylbenzyl)-3-[0-α-D-glucopyranosyl(1→4)-D-glucopyranosyl]urea (i.e. 1- (2-chloroethyl)-3-(2,4,6-trimethylbenzyl)-3-(D-maltosyl)urea)8.
Obtain Of as a colorless powder.

IRv: Yen 01 (Crfi-1): 3310, 1610
, 1530, 1070, 1030NMR (D6-D
MSO): 2.24 (S, CU,) 2.30 (S,
CU3) 2.88 (S, phenyl proton) ). )1-(2-chloroethyl)-3-(2,4,6-
Trimethylbenzyl)-3-[0-α-D-glucopyranosyl(1→4)-D-glucopyranosyl]urea5.
8 g was suspended in a mixture of 150 ml of tetrahydrofuran and 20 ml of acetic acid, and 20 y of anhydrous sodium acetate was added.

8V of nitrogen tetroxide gas is passed through this at -5°C to 0°C for 10 minutes while stirring. After further stirring at the same temperature for two minutes, 200 TfL of n-hexane was added, insoluble matter was filtered off, and the filtrate was concentrated to remove the solvent. Add 200ml of a mixture of ether and methanol (20:1) to the resulting residue.
1 was added, the precipitated oil was collected and chromatographed on silica gel (solvent: ethyl acetate-chloroform-methanol (2:
1:1)). 1-(2-chloroethyl)-1
-tetroso-3-(2,4,6-trimethylbenzyl)
-3-[0-α-D-glucopyranosyl(1→4)-
D-glucopyranosyl]urea (i.e. 1-(2-chloroethyl)-1-nitroso-3-(2,4,6-trimethylbenzyl)-3-(D-maltosyl)urea)4.
5y is obtained as a pale yellow powder.

M. P. 76 Ru C-80 Urine C (decomposition) IRv to 1030 NMR (D2O) δ: 2.15 (S, C)
2.12 (S, CU3) 6.75 (S, phenyl proton) [α]? +12.00 (C=1.0N methanol) Example 8 (1) D-maltose monohydrate 7.2f,. P-
4.1y of methoxybenzylamine and 3.0y of 2-chloroethyl isocyanate were treated in the same manner as in Example 1-(1) to obtain 1-(2-chloroethyl)-3-(P-methoxybenzyl)-3- [0-α-D-glucobylanosyl(1→4)-D-glunicopyranosyl]urea (i.e. 1-(2-chloroethyl)-3-(P-methoxybenzyl)-3-(D -maltosyl)urea) 7.4y is obtained as a colorless amorphous powder.

IRV=Xrl(Cm-1):332011 0, 15
30, Town 1080, 1030 NMR (D2O) δ:
3.80 (S, aim, 7.20 (Q, 4H, phenyl proton) (2) 1-(2-chloroethyl)-3-(P-methoxybenzyl)-3-[0-α-D-glucopyra Nosyru(1→4)-D-glucopyranosyl]urea 5.7f
and nitrogen tetroxide gas 8f were treated in the same manner as in Example 1-(2) to obtain 1-(2-chloroethyl)-1-nitroso-3-(P-methoxybenzyl)-3-[0-a- D-
Glucopyranosyl(1→4)-D-glucopyranosyl]urea (i.e. 1-(2-chloroethyl)-1-nitroso-3-(P-methoxybenzyl)-3-(D-maltosyl)urea) 4.1f is obtained as a pale yellow powder.

M. P. 8 (generation) -86℃ (decomposition) IRv or more 01 (Cm-1): 1690 to 335, 10
70, 1030NMR (D6-DMSO): 3.75 (
S, 3H, l. l5 (Q, 4H, phenyl proton) [
α〕r+29.7 (C=1.1, methanol) k Example 9
1) D-maltose monohydrate 7.2y1 (2,3-dimethoxybenzyl)amine 4.29y and 2-chloroethyl isocyanate 2.5y were treated in the same manner as in Example 7-(1) to obtain 1 -(2-chloroethyl)-3-(2,3
-dimethoxybenzyl)-3-[0-α-D-glucopyranosyl(1→4)-D-glucopyranosyl]urea (
That is, 1-(2-chloroethyl)-3-(2,3-dimethoxybenzyl)-3-(D-maltosyl)urea)
8.1y is obtained as a colorless caramel.

IRv: Yen 01 (C7?t-1): 335011635
, 1530, 1070, 1020NMR (D2O)
δ: 3.8 (S, OCH3) 6.9-7.2 (M,
phenyl proton)))1-(2-chloroethyl)-3
-(2,3-dimethoxybenzyl)-3-[0-α-D
-Glucopyranosyl(1→4)-D-glucopyranosyl]urea and nitrogen tetroxide gas 8y were treated in the same manner as in Example 7-(2), and 1-(2-chloroethyl)-1-nitroso3- (2,3-dimethoxybenzyl)-3-[0-
α-D-glucopyranosyl(1→4)-D-glucopyranosyl]urea (i.e., 1-(2-chloroethyl)
-1-nitroso-3-(2,3-dimethoxybenzyl)
-3-(D-maltosyl)urea) 3.69 is obtained as a pale yellow powder.

M. P. 67C one tin °C (decomposition) IRv = 01 spoon (C!fl-Lini 3375.1705s
1070NMR (D2O) δ: 3.8 (S, OCH3)
6.9-7.2 (M, phenyl proton) [α] A+32.1 ((C = 1.0, methanol) Example 10 (
1) D-maltose Monohydrate 7.2y1 (3,4,5
-trimethoxybenzyl)amine 8.0f1 and 2-
Example 7-(1) chloroethyl isocyanate 2.5f
) to give 1-(2-chloroethyl)-3-
(3,4,5-trimethoxybenzyl)-3-[0-α
-D-glucopyranosyl(1→4)-D-glucopyranosyl]urea (i.e. 1-(2-chloroethyl)-
3-(3,4,5-trimethoxybenzyl)-3-(D
-maltosyl)urea) 9.5V is obtained as a colorless powder.

IRp:? 01(Cm-1):33701164011
595, 1505, 1120, 1070NMR (D
2O) δ: 3.86 (S, 9H, OCJ: 13) 6
．． 83 (S, 2H, phenyl proton) (2) 1-(2
-chloroethyl)-3-(3,4,5-trimethoxybenzyl)-3-[0-α-D-glucopyranosyl(1
→4) -D-glucopyranosyl]Urea 5.2V and nitrogen tetroxide gas 8y were treated in the same manner as in Example 7-(2), and 1
-(2-chloroethyl)-1-nitroso3-(3,4
,5-trimethoxybenzyl)-3-[0-α-D-glucopyranosyl(1→4)-D-glucopyranosyl]
Urea (i.e. 1-(2-chloroethyl)-1-nitroso-3-(3,4,5-trimethoxybenzyl)-3
-(D-maltosyl)urea) 4.0y is obtained as a pale yellow powder.

M. P. 98℃ (decomposition) More than IRv? 01(An-1):338011695,1
590, 1500, 112 length 1070, 1050s
1030NMR (D2O) δ: 3.82 (S,9H,O
C-dan.

) 6.75 (S, 2H, phenyl proton) [α]
e+23.7 (C=1.methanol) Example 11 (1
) D-maltose monohydrate 7.2y1 (P-hydroxybenzyl)amine 3.0f and 2-chloroethyl isocyanate 2.5y were treated in the same manner as in Example 7-(1) to obtain 1-(2 -chloroethyl)-3-(P-hydroxybenzyl)-3-[0-α-D-glucopyranosyl(1→4)-D-glucopyranosyl]urea (i.e.
Obtain 5.7f of 1-(2-chloroethyl)-3-(P-hydroxybenzyl)-3-(D-maltosyl)urea) as colorless caramel IRv 01 ([-1): 336
0, 1630, 10, 1510, 102 to 107
0NMR (D2O) δ: 6.82 (D, 2H, phenylproton) 7.22 (D, 2H, phenyl proton) 1-(2-chloroethyl)-3-(P-hydroxybenzyl)- 3-[0-α-D-glucopyranosyl(1→4)-D-glucopyranosyl]urea 5.5
V and nitrogen tetroxide gas 8y were treated in the same manner as in Example 7-(2) to produce 1-(2-chloroethyl)-1-nitroso 3
-(P-hydroxybenzyl)-3-[0-α-D-glucopyranosyl(1→4)-D-glucopyranosyl]
2.4y of urea (i.e. 1-(2-chloroethyl)-1-nitroso-3-(P-hydroxybenzyl)-3-(D-maltosyl)urea) is obtained as a pale yellow powder.

M. P. 74℃ (decomposition) IRv 01 (Crfl-1): 336011700
11070110 mark, 1025NMR (D2O) δ
:7.04 (D, 2H, Fenilpu mouth ton)
7.56 (D, 2H, phenyl proton) [α]■+4
7.62 (C=1. methanol) Example 12i) D-
Maltose monohydrate 7.2V1 (P-nitrobenzyl)amine 4.5y and 2-chloroethyl isocyanate 2.5f were treated in the same manner as in Example 7-(1) to obtain 1-
(2-chloroethyl)-3-(P-nitrobenzyl)-
3-[0〒α-D-glucopyranosyl(1→4)-D
niglucopyranosyl]urea (i.e., 1-(2-chloroethyl)-3-(P-nitrobenzyl)-3-(D-
Maltosyl) urea&0y is obtained as a pale yellow powder.

IRv = Yen 01 (Cffl-1): 3350, 1640
, 160011515, 1345s1070s10
25NMR (D2O) δ: 7.58 (D, 2H, phenyl proton) &14 (D, 2H, phenyl proton) 2) 1-(2-chloroethyl)-3-(P-
nitrobenzyl)-3-[0-α-D-glucopyranosyl(1→4)-D-glucopyranosyl]urea 5.8y
and nitrogen tetroxide gas 8' were treated in the same manner as in Example 7-(2) to obtain 1-(2-chloroethyl)-1-nitroso 3-
(P-nitrobenzyl)-3-[0-α-D-glucopyranosyl(1→4)-D-glucopyranosyl]urea (i.e. 1-(2-chloroethyl)-1-nitroso3
-(P-nitrobenzyl)-3-(D-maltosyl)urea) 3.8y is obtained as a pale yellow powder.

M. p. 8rc-8 (generation) (disassembly) IRv 01 (Crfl-1): 3370, 1700
, 1600, 1515, 1345s1070s10
5 to 1030 NMR (D2O) δ: 7.44 (D,2H
, Fenilpu mouthton) 7.90 (D, 2H,
phenyl proton) [α] r + 10.52 (C = 1. methanol) Example 13 (1) D-maltose monohydrate 7.211 phenethylamine 3.2y and 2-chloroethyl isocyanate 3.0y Example 1-(1) to obtain 1-(2-chloroethyl)-3-phenethyl-3-[0-α-D-glucopyranosyl(1→
4) -D-glucopyranosyl]urea (i.e. 1-(
2-chloroethyl)-3-phenethyl-3-(D-maltosyl)urea) 7.1f is obtained as a colorless amorphous powder.

IRp Sakai 01 (Cm-1): 333011640115
3011070, 1020NMR (D2O) δ: 7
．． 3 (prode S, phenyl. proton) (2) 1-(
2-chloroethyl)-3-phenethyl-3-[0-α-
D-glucopyranosyl(1→4)-D-glucopyranosyl] 5.3 y of urea and 8 y of nitrogen tetroxide gas were added in Example 1-
Treated in the same manner as (2) to produce 1-(2-chloroethyl)
-1-nitroso-3-phenethyl-3-[0-α-D-
3.8y of glucopyranosyl(1→4)-D-glucopyranosyl]urea (i.e., 1-(2-chloroethyl)-1-nitroso-3-phenethyl-3-(D-maltosyl)urea) as a pale yellow powder. obtain.

M. P. 77C-75℃ (decomposition) IRv: Todoroki 01 (Cm-1): 335 to 169 to 107
to 1020NMR (D2O) δ: 7.25 (Prode S
, phenyl proton) [α] r+58.6: (C=1.
1, methanol) Example 141) D-maltose. Monohydrate 7.2y1 α-methylbenzylamine 4.0f1 and 2-chloroethyl isocyanate 2.5y were treated in the same manner as in Example 7-(1) to obtain 1-(2-chloroethyl)-3-(methyl benzyl)-3-[0-α-D-glucopyranosyl(1→4)-D-glucopyranosyl]urea (i.e. 1-(2-chloroethyl)-3-(α-
methylbenzyl)-3-(D-maltosyl)urea)8.
8f is obtained as a colorless caramel.

IRv: Yen 01 (d-1): 50, 1630, 152
5, 1070, 1030NMR (D6-DMSO)
δ: 1.2-1.8 (M, 3H, C...3) 7.3 (
S, 5H, phenyl proton) 2) 1-(2-chloroethyl)-3-(α-methylbenzyl)-3-[0-α-
D-glucopyranosyl(1→4)-D-glucopyranosyl] 5.5f of urea and 8.0y of nitrogen tetroxide gas were treated in the same manner as in Example 7-(2) to obtain 1-(2-chloroethyl). -1-nitroso3-(α-methylbenzyl)-3-
[0-α-D-glucopyranosyl(1→4)-D-glucopyranosyl]urea (i.e. 1-(2-chloroethyl)-1-nitroso-3-(α-methylbenzyl)-
3-(D-maltosyl)urea) 3.8y is obtained as a pale yellow powder.

M. P. ll (yo) (decomposition) ■ν=′:1. .

1 (ClR-1): 338 to 169 to 107 to 1030
NMR (D2O) δ: 1.50-1.84 (M, 3H,
CH3) 7.04-7.56 (M, 5H, phenyl proton) [α] r + 45.55 (C = 1.1,
methanol) Example 151) D-maltose Monohydrate 7.2f1 Tetrahydrofurfurylamine 3.6y and 2-chloroethyl isocyanate 2.5f Example 1
- Treated in the same manner as in (1) to produce 1-(2-chloroethyl)
-3-Tetrahydrofurfuryl-3-[0-α-D-glucopyranosyl (1→4)-D-glucopyranosyl]
Urea (i.e. 1-(2-chloroethyl)-3-tetrahydrofurfuryl-3-(D-maltosyl)urea) 7
．． 5y is obtained as a colorless amorphous powder.

■Rp! H Mi 01 (0-1): 337 to 164 to 154
to 1070NMR (D2O) δ: 1.75-2.25(
M, (2) 1-(2-chloroethyl)-3-tetrahydrofurfuryl-3-[0-α-D-glucopyranosyl-(1→4)-D-glucopyranosyl] urea 5.3' and nitrogen tetroxide Gas 8y was treated in the same manner as in Example 1-(2) to obtain 1-(2-chloroethyl)-1-nitroso-3-tetrahydrofurfuryl-3-[0-α-D-glucopyranosyl(1→ 4) -D-glucopyranosyl]urea (i.e. 1-(2-chloroethyl)-1-nitroso3)
-tetrahydrofurfurfuryl-3-(D-maltosyl)urea) 4.1f1 is obtained as a pale yellow powder.

M. P. 69'C-71℃ (decomposition) IRv? : Spoon 01 (CwL-1): 335 to 170 to 1
060NMR(D2O)δ:1.7-2.2(M,4H
,4.2O(T,2H,-N(NO)-Cu,-)[α
]? +52.5, (C=1.2, methanol);
Example 16 (1) D-maltose monohydrate 7.2y1
(1,3-dioxolane-4-yl-methyl)amine (
(obtained by catalytic reduction of 1,3-dioxolane-4-ylmethyl) azide) and . 2.5 g of 2-chloroethyl isocyanate was treated in the same manner as in Example 7-(1) to obtain 1-(2-chloroethyl)-3-(1,
3-dioxolane-4-yl-methyl)-3-[0-α
-D-glucopyranosyl(1→4)-D-glucopyranosyl]urea (i.e. 1-(2-chloroethyl)-
3-(1,3-dioxolan-yl-methyl)-3-[
0-α-D-glucopyranosyl(1→4)-D-glucopyranosyl]urea (i.e. 1-(2-chloroethyl)-3-(1,3-dioxolan-4-ylmethyl)-3-(D- 5.8 g of maltosyl (urea) are obtained as a colorless powder.

IRv=yen 01 (C!fl-1): 3350, 1640
, 154011150, 108 to 1030). )1
-(2-chloroethyl)-3-(1,3-dioxolan-4-ylmethyl)-3-[0-α-D-glucopyranosyl(1→4)-D-glucopyranosyl]urea5.
3f and nitrogen tetroxide gas 8y were treated in the same manner as in Example 7-(2) to obtain 1-(2-chloroethyl)-1-nitroso-3-(1,3-dioxolan-4-yl-methyl)-3.
-[0-α-D-glucopyranosyl(1→4)-D-
glucopyranosyl]urea (i.e. 1-(2-chloroethyl)-1-nitroso-3-(1,3-dioxolan-4-yl-methyl)-3-(D-maltosyl)urea)
3.6V is obtained as a pale yellow powder.

M. P. 67C-64℃ (decomposition) IRv: Yen 01 (d-1): 335011700, 11
501108011030NMR(D2O)δ:4.2
0(T, -N(NO)CH-) [α]? +48.62(
C=1.2, methanol) history Example 17:1) D-maltose monohydrate 7.2y1 (1,3-dioxolane-2
2.5y of 1-(2-chloroethyl)-3-(1,3-
dioxolan-2-yl-methyl)-3-[0-α-D
-glucopyranosyl(1→4)-D-glucopyranosyl]urea (i.e. 1-(2-chloroethyl)-3-
(1,3-dioxolane-2-yl-methyl)-3-(
6.5 fI of D-maltosyl) urea are obtained as a colorless caramel.

IRv = Yen 01 (Cm-1): 3350, 1650, 1
540, 1070, 1020 (2) 1-(2-chloroethyl)-3-(1,3-dioxolan-2-ylmethyl)-3-[0-α-D-glucopyranosyl(1
→4)-D-Glucopyranosyl] 5.3y of urea and 8g of nitrogen tetroxide gas were treated in the same manner as in Example 7-(2), and 1
-(2-chloroethyl)-1-nitroso-3-(1,3
-dioxolane-2-yl-methyl)-3-[0-α-
D-glucopyranosyl(1→4)-D-glucopyranosyl]urea (i.e. 1-(2-chloroethyl)-1
-Nitroso-3-(1,3dioxolan-2-yl-methyl)-3-(D-maltosyl)urea) 3.2y is obtained as a pale yellow powder.

M. P. 85℃-90℃ (decomposition) IRv: Snake 01 (d-1): 337 to 170 1040
[α]r+52.8-(C=1.0, methanol) Example 18 (1) D-maltose Monohydrate 7.2y1 (1
,4-dioxane-2-ylmethyl)amine 2.5y
and 2-chloroethyl isocyanate 2.5f were treated in the same manner as in Example 7-(1) to produce 1-(2-chloroethyl)-3-(1,4-dioxan-2-yl-methyl).
-3-[0-α-D-glucopyranosyl(1→4)-
D-glucopyranosyl]urea (i.e. 1-(2-chloroethyl)-3-(1,4-dioxan-3-yl-methyl)-3-(D-maltosyl)urea) 6.3f is obtained as a colorless caramel.

IRv: Spoon 1 (c!n-1): 3350, 1640,
1540, 1120, 1080, 1030 (2) 1-(
2-chloroethyl)-3-(1,4-dioxane-2-
5.4y of urea and 8f of nitrogen tetroxide gas were treated in the same manner as in Example 7-(2). ．． 1-(2-chloroethyl)-1-nitroso-3-(1,4-dioxan-2-ylmethyl)-3
-[0-α-D-glucopyranosyl(1→4)-D-
glucopyranosyl]urea (i.e., 1-(2-chloroethyl)-1-nitoroso-3-(1,4-dioxan-2-ylmethyl)-3-(D-maltosyl)urea)
3.6f is obtained as a pale yellow powder.

M. P. 74-terminal c-7rC (degradation) IRv or higher? 01(C7R-1):3350, 1700,
1120, 1080, -1040[α]W+43.
8C' (C=1.0s methanol) Example 19 (1)
D-maltose Monohydrate 7.2g, Tetrahydro S
, S-dioxo-3-thienylmethylamine (C.S.
Argyletal. , J. Chem. SOc. ,2
156 (1967)) 3.6y and 2-chloroethyl isocyanate 2.5f were treated in the same manner as in Example 1-(1) to obtain 1-(2-chloroethyl)-3-(tetrahydro S,S-dioxo 3 -thienylmethyl)-3-[
0-α-D-glucopyranosyl(1→4)-D-glucopyranosyl]urea (i.e. 1-(2-chloroethyl)-3-(tetrahydro S,S-dioxo-3-thienylmethyl)-3-( D-maltosyl) urea) 6.4
y is obtained as a colorless amorphous powder.

IRv: Yen 01 (Cm-1): 50, 1630, 1?
0, 1300, 1120, 10402 to 108) 1
-(2-chloroethyl)-3-(tetrahydroS,S
-dioxo-3-thienylmethyl)-3-[0-α-D
-Glucopyranosyl(1→4)-D-glucopyranosyl]urea 5.8V and nitrogen tetroxide gas 8fI Example 1-
Treated in the same manner as (2), 1-(2-chloroethyl)-
1-Nitroso-3-(tetrahydro-S,S-dioxo-3-thienylmethyl)-3-[0-α-D-glucopyranosyl(1→4)-D-glucopyranosyl]urea (
That is, 1-(2-chloroethyl)-1-nitroso-3-(tetrahydro S,S-dioxo-3-thienylmethyl)-3-(D-maltosyl)urea) 3.9V is obtained as a pale yellow powder.

M. P. 74℃-7TC (decomposition) ■Rv: Yen 01 (c1-1): 335011700, 1
30011120, 1030 [α] D+4 to 108
2.00 (C = 1. methanol) - Example 201) D
-maltose monohydrate 7.2y1 furfurylamine 5
．． 8f and 2-chloroethyl isocyanate 4.0'
was treated in the same manner as in Example 1-(1) to obtain 1-(2-chloroethyl)-3-furfuryl-3-[0-α-D-glucopyranosyl-(1-4)-D-glucopyranosyl]urea. (i.e., 1-(2-chloroethyl)-3-furfuryl-3-(D-maltosyl)urea) 6.4f is obtained as a colorless amorphous powder.

M. P. lO, 3C (decomposition) IRp = yen 01 (0-linio 50, 160, 1 seki 0, 1
070, 1030NMR (D2O) δ: 6.46 (
M, 2H, furan ring) 7.53 (M
, 2H, furan ring proton) (2) 1-(2-chloroethyl)-3-furfuryl-3-[0-α-D-glucopyranosyl-(1→4)-D-glucopyranosyl) urea 5
．． 3f and nitrogen tetroxide gas 8y were treated in the same manner as in Example 1-(2) to obtain 1-(2-chloroethyl)-1-nitroso-3-furfuryl-3-[0-α-D-glucopyranosyl- (1→4)-D-glucopyranosyl]urea (i.e. 1-(2-chloroethyl)-1-nitroso3-
3.9 Da of furfuryl-3-(D-maltosyl)urea) is obtained as a pale yellow powder.

M. P. 54℃ (decomposition) 1Rv heart? 01 (0-1): 170 to 335 to 108 1030 NMR (D2O) δ: 6.43 (M, 2H, furan ring proton) 7.45 (M, IH, furan ring proton) [α]♂+27 .5I (C=1.0, methanol) Example 21 (1) D-maltose monohydrate 7.2f1 (thiophen-2-ylmethyl)amine 2
．． 7y and 2-chloroethyl isocyanate 2.5f
was treated in the same manner as in Example 7-(1) to obtain 1-(2-chloroethyl)-3-(thiophen-2-ylmethyl)-
3-[0-α-D-glucopyranosyl(1→4)-D
-glucopyranosyl)urea (i.e. 1-(2-chloroethyl)-3-(thiophen-2-ylmethyl)-
3-(D-maltosyl)urea) 7.6y is obtained as a colorless caramel.

IRvshi01(d-1):3?011620, 1530
, 1070, 1020NMR (D2O) δ: 6.9
-7.2 (M, 2H, 7.3-7.5 (M, lH,).
)1-(2-chloroethyl)-3-(thiophene-2-
5.4y of urea and 8f of nitrogen tetroxide gas were treated in the same manner as in Example 7-(2). , 1-(2-chloroethyl)-1-nitroso-3-(
Thiophen-2-yl-methyl)-3-[0-α-D-glucopyranosyl-(1→4)-D-glucopyranosyl]urea (i.e. 1-(2-chloroethyl)-1-nitroso-3-(thiophene-2- methyl)-3-
(D-maltosyl)urea 3.2y is obtained as a pale yellow powder.

M. P. 6O℃-65℃ (decomposition) Translation ν? Kabuto 01 (Cm-1): 107 to 3375s170
0NMR(D2O)δ:6.9-7.5(M,2H,''
．． 3-7.5(M, lH, [α]K+4&0M(C=1
．． Example 1) D-maltose monohydrate 7.2y 14-pyridylmethylamine 3.2V and 2-chloroethyl isocyanate 3.0y Example 1
- Treated in the same manner as in (1) to produce 1-(2-chloroethyl)
-3-(4-pyridylmethyl)-3-[0-α-D-glucopyranosyl(1→4)-D-glucopyranosyl]
Urea (i.e. 1-(2-chloroethyl)-3-(4
-pyridylmethyl)-3-(D-maltosyl)urea)6
．． 2fI is obtained as a colorless caramel.

■Rp 01 (C7l-1): 3330, 1640,
1530, 1080, 1030NMR (4-DMS
O) δ: 7.50 (M, 2H, pyridine ring proton) &50 (M, 2H, pyridine ring proton (2)
1-(2-chloroethyl)-3-(4-pyridylmethyl)-3-[0-α-D-glucopyranosyl(1→4)
-D-glucopyranosyl]urea 5.4V and nitrogen tetroxide gas 8y were treated in the same manner as in Example 1-(2),
-chloroethyl)-1-nitroso3-(4-pyridylmethyl)-3-[0-α-D-glucopyranosyl(1
→4)-D-glucopyranosyl]urea (i.e. 1-
(2-chloroethyl)-1-nitroso-3-(4-pyridylmethyl)-3-(D-maltosyl)urea) 5.1f
1 is obtained as a pale yellow powder.

M. P. 75°C-78°C (decomposition) IRvR 01 (c'Rini 3300, 170 to 107 to 1040 NMR (D6-DMSO) δ: 7.50 (M,
2H, pyridine ring proton) 8.55 (M,
2H, pyridine ring proton) [α]♂+40.1
2 (C=0. & methanol) Example 23 (1) A mixture of 3.6 da of D-galactose, 10 y of cyclohexylamine and 20 ml of methanol is heated and stirred at 60°C for 1 hour.

After the reaction, the reaction solution is concentrated to dryness under reduced pressure, and the residue is washed with ether. 5.2y of 1-cyclohexylamino-1-deoxy-D-galactose is obtained as a crude product.

5.2y of this crude product was dissolved in 50ml of methanol, and a solution of 2.3y of 2-chloroethyl isocyanate dissolved in 10ml of tetrahydrofuran was added at 0°C to 5°C.
Add dropwise and stir at room temperature for 1 hour. The reaction solution was concentrated under reduced pressure, and the resulting residue was dissolved in 20 ml of formic acid. After leaving two formic acid solutions at room temperature, ether-n-hexane (
Add 150ml of the 3:1) mixture. The precipitated oil was chromatographed on silica gel (solvent: chloroform-ethyl acetate).
Purify with methanol (3:1:1). 3.2y of 1-(2-chloroethyl)-3-cyclohexyl-3-(D-galactopyranosyl)urea is obtained as a colorless caramel.

IRp to 01 (106 to 1M to 1M to Rini 336
0NMR (D2O) δ: 1.0-2.0 (M, lOH,
2) Dissolve 3.7 f of 1-(2-chloroethyl)-3-cyclohexyl-3-(D-galactopyranosyl)urea in a mixture of 60 ml of tetrahydrofuran and 60 ml of methylene chloride, and add 15 f of anhydrous sodium carbonate.

After stirring and cooling with ice, 5y of nitrogen tetroxide gas was passed through the mixture, and the mixture was further stirred at the same temperature. After the reaction, 10 ml of methanol and 3 ml of water were added to the reaction solution, and the mixture was stirred vigorously. The reaction solution is dried and filtered, the filtrate is concentrated, the solvent is distilled off, and the resulting residue is purified by silica gel chromatography (solvent: ethyl acetate-chloroform-methanol (5:2:1)). 1-(2-chloroethyl)-1-nitroso-3-cyclohexyl-3-(
D-galactopyranosyl) urea 2.8y is obtained as a yellow caramel.

Translation ν? Spoon 01 (1060N to d-lini 3400s169
MR(D2O)δ: 0.9-2.2(M, [α]r+2
1.6: (C=1.3s methanol) Example 24i) D
- Galactose 3.6fI1 cyclopropylmethylamine 2.2y and 2-chloroethyl isocyanate 2.
5f was processed in the same manner as in Example 23-(1) to obtain 1-(2
-chloroethyl)-3-cyclopropylmethyl-3-(
D-galactopyranosyl) urea 4.5y is obtained as a colorless caramel.

Claw ν=Spoon 01 (Cm-Lini O5 to 164 to 1 neighbor\106
0NMR (D2O) δ: 0.35-0.75 (M, 4H
,') 1-(2-chloroethyl)-3-cyclopropylmethyl-3-(D-galactopyranosyl) urea 3.4f
and nitrogen tetroxide gas 5' were treated in the same manner as in Example 23-(2) to produce 1-(2-chloroethyl)-1-nitroso-3-cyclopropylmethyl-3-(D-galactopyranosyl). Urea 2.6f is obtained as yellow caramel. I
RvZ spoon 01 (C!11-1): 3 birds to 169 to 109
0NMR (D2O) δ: 0.3-0.7 (M, 4H, [
α]r+18.6: (C=1.34, methanol) Example 2511 (1) D-galactose 3.6f1 cyclohexylmethylamine 4.5y and 2-chloroethyl isocyanate 2.5y Example 23-(1) 1-(2-chloroethyl)-3-cyclohexylmethyl-3-(D-galactopyranosyl)urea 4.
7y is obtained as a colorless caramel.

IRv% spoon 01 (C7n-1): 1 to 3350N164
54 length 1070NMR (D2O) δ: 0.6-2.0(
M, llH, cyclohexyl ring proton) (2
) 3.8 f of 1-(2-chloroethyl)-3-cyclohexylmethyl-3-(D-galactopyranosyl) urea and 5 g of nitrogen tetroxide gas were treated in the same manner as in Example 23-(2) to obtain 1 -(2-chloroethyl)-1-nitroso3-
2.82y of cyclohexylmethyl-3-(D-galactopyranosyl)urea is obtained as a pale yellow powder.

M. P. 68°C (decomposition) IRv or higher? 01 (c!n-1): 340 to 169 to 10
80NMR (D6-DMSO) δ: 0.6-2.0 (M
, llH, cyclohexyl ring proton). [
α]f-11.5ro (C=1.0s methanol) Example 26 (1) D-galactose 3.6y1 benzylamine 3.2y and 2-chloroethyl isocyanate 3.0
1-(2-
4.9f of chloroethyl)-3-benzyl-3-(D-galactopyranosyl)urea is obtained as a colorless caramel.

IRvimi01 (Cm-1): 335 to 164 to 154
1 edict ONMR (D2O) δ: 4.73 (S, 2H,)
．． )1-(2-chloroethyl)-3-benzyl-3-(
3.8y of D-galactopyranosyl) urea and 5y of nitrogen tetroxide gas were treated in the same manner as in Example 23-(2) to produce 1-(
2-chloroethyl)-1-nitroso-3-benzyl-3
-(D-galactopyranosyl)urea 2.8y is obtained as yellow caramel.

Take ν or more spoon 0] (Crfi-1): 3 edicts 169\108
0qMR (D6-DMSO): 4.64 (S, 2H, 7
．． 29 (S, 5H, phenyl proton) [α]? -22
．． 6, (C=1.5N methanol) Example 27 (1) D
- galactose 3.6f1 tetrahydrofurfurylamine 4.0f1 and 2-chloroethyl isocyanate 2
．． 5y was treated in the same manner as in Example 23-(1) to obtain 1-(
2-chloroethyl)-3-tetrahydrofurfuryl-3
5.0y of -(D-galactopyranosyl)urea is obtained as a colorless caramel.

IRv? ? 01(c!Ri-1):3370, 185,
1?0, 1070, 1040NMR(D2O)δ
:1.8-2.3(M, (2) 1-(2-chloroethyl)-3-tetrahydrofurfuryru-3-(D-galactopyranosyl)urea 3.7f and nitrogen tetroxide gas 6y Example 23-(2) to obtain 2.9y of 1-(2-chloroethyl)-1-nitroso-3-tetrahydrofurfuryl-3-(D-galactopyranosyl)urea as a yellow caramel.

Shaku J (spoon 01 (Cm-1): 3 songs to 170 to 1060N
MR (D2O) δ: 1.75-2.25 (M, [α]♂
+16.6: (C = 1st methanol) Example 28 (1
) D-galactose 3.6f1 (3-morpholinoprene01no)7S'-157q 3.0 g of γ-do 2-chloroethinolysocyanate was treated in the same manner as in Example 23-(1) to obtain 1- 3.5y of (2-chloroethyl)-3-(3-morpholinopropyl)-3-(D-galactopyranosyl)urea is obtained as a colorless caramel.

IRv to 1 (c! n-1): 335 to 1 trouble 1S 1070 NMR (D2O) δ: 1.8-2.3 (M, 2
H,〉N- CH2-CU,CH2N〈) 2.7-3
．． 2(M,6H, (2)1-(2-chloroethyl)-3-(3-morpholinopropyl)-3-(D-galactopyranosyl)urea 4
．． 1f and nitrogen tetroxide gas 5f in Example 23-(2)
1-(2-chloroethyl)-1-nitroso-3-(3-morpholinopropyl)-3-(D-
Galactopyranosyl) urea 2.4y is obtained as a yellow caramel.

IRv: Spoon 01 (Cm-1): 11 to 34001170
2 to 1070 NMR (D2O) δ: 1.8-2.3 (M
,2H,〉N-CH2-CH2CH2N)
2.6-3.0 (M, 6H, [α] f + 12.60 (C = 1. methanol) Example 29 (1) D-galactose 5.5', furfurylamine 3.8y and 2-chloroethyl Isocyanate 3.
5y was treated in the same manner as in Example 23-(1) to obtain 1-(2
-chloroethyl)-3-furfuryl-3-(D-galactopyranosyl) urea (6.7 fI) is obtained as a colorless powder.

Translation ν is 01 (C7l-1): 335 to 164 to 1% ONMR (D2O) δ: 4.60 (S, 2H, 6.
45 (M, 2H, furan ring proton) 7.45 (M, l
H, furan ring proton) (2) 1-(2-chloroethyl)-3-furfuryl-3-(D-galactopyranosyl)
Example 23-(2
) to give 1-(2-chloroethyl)-1-
2.8y of nitroso-3-furfuryl-3-(D-galactopyranosyl)urea is obtained as a yellow caramel.

Translation ν = spoon 01 (C! fl-lini 3 ahe 169 to 1070
NMR (D2O) δ: 5.15 (D, lH, Cl-H)
6.40 (M, 2H, furan ring proton)
7.40 (M, lH, furan ring proton) [α]? -2
．． 5M (C=1.2, methanol) Example 30) 1) L
-arabinose 3.0y1 cyclopropylmethylamine 2.2V and 2-chloroethyl isocyanate 2.5
g was treated in the same manner as in Example 23-(1) to obtain 1-(2-
chloroethyl)-3-cyclopropylmethyl-3-(L
-arabinopyranosyl) urea 2.4f is obtained as a colorless caramel.

IRv=Spoon 01 (Crft-1): 335 to 164 to 1
53 length 1060NMR (D2O) δ: 0.35-0.7
5(M,4H,2)1-(2-chloroethyl)-3-cyclopropylmethyl-3-(L-arabinopyranosyl)
Example 23-(2) Urea 3.1f and nitrogen tetroxide gas 5y
) to give 1-(2-chloroethyl)-1-
2.4y of nitroso-3-cyclopropylmethyl-3-(L-arabinopyranosyl)urea is obtained as a yellow caramel. ■ν or more spoon 01 (1090 to d-linia 201170
NMR (D2O) δ: 0.2-0.8 (M, 4H, [α
]? +54.7: (C=1.2, methanol) Example 3
1) L-arabinose 3.0f1 benzylamine 4.3
A mixture of Y and 10 ml of methanol is heated and stirred at 60° C. for 1 hour.

After the reaction, the reaction solution is concentrated to dryness under reduced pressure and the residue is washed with ether. 4.7 units of 1-benzylamino-1-deoxy-L-arabinose are obtained as a crude product.

4.7y of this crude product was dissolved in 30ml of methanol, and a solution of 2.5V of 2-chloroethyl isocyanate dissolved in 10ml of tetrahydrofuran was added at 0°C to 5°C.
Add the mixture and stir for 1 hour at room temperature. The reaction solution was concentrated under reduced pressure, and the resulting residue was dissolved in 15 ml of formic acid. After leaving 1 part of formic acid solution at room temperature, ether-n-hexane (1 part) was added.
:1) Add 150ml of mixed liquid. The precipitated oil was separated by decanting, washed with ether, and then subjected to silica gel chromatography (
Solvent: Chloroform-ethyl acetate-methanol (2:5
:1)). 1-(2-chloroethyl)-3-
Benzyl-3-(L-arabinopyranosyl)urea 6.2
y is obtained as a colorless caramel.

IRv: 01 (Crn-Rini 335 to 164 to 153
to 1090NMR (D6-DMSO) δ: 7.30 (S
, phenyl-proton) (2) 3.4 fI of 1-(2-chloroethyl)-3-benzyl-3-(L-arabinopyranosyl) urea was dissolved in a mixture of 60 ml of tetrahydrofuran and 60 ml of methylene chloride, and 15 y of anhydrous sodium carbonate was added. Add.

After passing 5 y of nitrogen tetroxide gas through the mixture under ice-cooling and stirring, the mixture is stirred at the same temperature. After the reaction, 10 ml of methanol and 3 ml of water were added to the reaction solution, and the mixture was stirred vigorously. The mixture is dried, filtered and the filtrate is concentrated to remove the solvent. The residue was chromatographed on silica gel (solvent: ethyl acetate-chloroformmethanol (5:
2:1)). 1-(2-chloroethyl)-1
2.8 g of -nitroso-3-benzy-3-(L-arabinopyranosyl)urea are obtained as yellow caramel.

Choice ν? ? 01 (C7l-Lini 340 169\1070
NMR (D6-DMSO) δ: 4.70 (S, 2H, 4
．． 86 (D, lH, Cl-H) 7.30 (S, 5H, phenyl proton) [α] F-15.6, (C = 2. methanol)? Example 32) L-arabinose 3.0y. s
Example 31-(1) 3.0y of P-methoxybenzylamine and 2.5y of 2-chloroethyl isocyanate
1-(2-chloroethyl)-3-(
5.6y of P-methoxybenzyl)-3-(L-arabinopyranosyl)urea is obtained as a colorless caramel.

IRv 01 (Crfl-1): 3350, 1630
, 1520, 1080NMR (D6-DMSO) δ:3
．． 70 (S, 3H, OCH3) 7.03 (ABq,
4H, phenylproton) 1-(2-chloroethyl)-3-(P-methoxybenzyl)-3-(L-arabinopyranosyl)urea 3.7f and nitrogen tetroxide gas 5.
0g was treated in the same manner as in Example 31-(2) to obtain 1-(2
-chloroethyl)-1-nitroso3-(P-methoxybenzyl)-3-(L-arabinopyranosyl)urea2.
5f is obtained as a yellow caramel.

Translation ν? Spoon 01 (Cm-1): 340 to 169\151 1080 NMR (D2O) δ: 3.70 (S, 3H, O
CN3) 4.60(S, 2H, .8O(D, lH,
Cl-H) ″.03 (ABq, 4H, phenyl proton) [α] f
-16.64 (C=1.methanol) Example 331)
L-arabinose 4.5y12-propenylamine 2.
5fI and 2-chloroethyl isocyanate 3.5y
was treated in the same manner as in Example 31-(1) to obtain 5.5f of 1-(2-chloroethyl)-3-(2-propenyl)-3-(L-arabinopyranosyl)urea as a colorless powder. obtain.

Translation ν is 01 (C7l-1): 334 to 1 Seki to 153 1 part ONMR (D2O) δ: 5.0-6.3 (M, .4
H, -CU=Cdan,,C, -H)2) 1-(2-chloroethyl)-3-(2-propenyl)-3-(L-arabinopyranosyl)urea 3.2y and tetroxide Nitrogen gas 5f was treated in the same manner as in Example 31-(2) to produce 1(2-chloroethyl)-1-nitroso-3-(2-propenyl)-3-
(L-arabinopyranosyl)urea 2.3y is obtained as a yellow caramel.

IRpH insect 01 (Crft-1): 340 to 170 to 1
080NMR(D2O)δ:4.9-6.3(M,4H
,-C. U=CH2,Cl-H)[α]r+12.8)
(C=1.λmethanol) (3) 1-(2-chloroethyl)-1-nitroso-3-(2-propenyl)-3-(
A mixture of 50 mt of methylene chloride and 50 m1 of benzene is stirred at room temperature for 3 hours.

After the reaction, the reaction solution is concentrated under reduced pressure, and the resulting residue is washed with ether and purified by silica gel chromatography (solvent: ethyl acetate). 1-(2-chloroethyl)-1-nitroso-3-(oxiran-2-ylmethyl)-3-(L
-arabinopyranosyl) urea 0.9y is obtained as a yellow caramel.

IRv: Snake 0] (Cm-1): 342 to 170 to 108
0NMR (D2O) δ: 2.70-3.05 (M, 3H
,4.2O(T,2H,-N(NO)Cdan,-)[α]
r+38.5, (C=0.5.methanol) Example 34
(1) 2.7 g of L-arabinose 3.0f1 (thiophene-2-ylmethyl)amine and 2.5y of 2-chloroethyl isocyanate were treated in the same manner as in Example 31-(1) to produce 1-(2-chloroethyl). -;3-(thiophen-2-yl-methyl)-3-(L-arabinopyranosyl)urea 4.1y is obtained as a colorless powder.

M. P. l35℃-140) C IRp 01 (Crll-1): 3490, 3395
, 3280, 1550, JlO95. lO65NMR (
D2O) δ: 7.0-7.3 (M, 2H, 7.4-7.
6(M,lH,(2)1-(2-chloroethyl)-3-
3.5 fI of (thiophen-2-yl-methyl)-3-(L-arabinopyranosyl) urea and 5.0 f of nitrogen tetroxide gas were treated in the same manner as in Example 31-(2). -chloroethyl)-1-nitroso-3-(thiophen-2-yl-methyl)-3-(L-arabinopyranosyl)urea 3.1f1 is obtained as a yellow powder.

M. P.槃℃-7CfC(decomposition) Translation ν Pass 713(Cm-Lini 340 to 170 to 1μSON
MR (D2O) δ: 7.0-7.3 (M, 2H, 7.4
-7.6(M, lH, [α]t+14.1, (C=1.
hemethanol) k Example 351) D-ribose 3.0f1
2.2y of cyclopropylmethylamine and 2.5y of 2-chloroethyl isocyanate were treated in the same manner as in Example 31-(1) to obtain 1-(2-chloroethyl)-3-cyclopropylmethyl-3-(D- ribopyranosyl) urea 4
．． 2y is obtained as a colorless caramel.

IRv or less ÷ t (0-1): 335 to 18 to 18
') 3.1y of 1-(2-chloroethyl)-3-cyclopropylmethyl-3-(D-ribopyranosyl)urea and 5y of nitrogen tetroxide gas were treated in the same manner as in Example 31-(2) to obtain 1 -(2-chloroethyl)-1-nitroso3
-cyclopropylmethyl-3-(D-ribopyranosyl)
2.3y of urea is obtained as a yellow powder.

IRvg? Id(Crn-1700 to Rini 345, 10
80NMR (D2O) δ: 0.20-0.70 (M, 4
H, [α]? -8.7 (C=1.2, methanol) Example 36 (1) D-ribose 3.0y1 furfurylamine 2.8fI and 2-chloroethyl isocyanate 2.
5y was treated in the same manner as in Example 31-(1) to obtain 1-(2
4.3y of (monochloroethyl)-3-furfuryl-3-(D-ribopyranosyl)urea is obtained as a colorless caramel.

IRp: Shima 13 (c!n-1): 340 to 165 to 15
2 to 1080 NMR (D2O) δ: 6.40 (M, 2H
, (2) 3.3y of 1-(2-chloroethyl)-3-furfuryl-3-(D-ribopyranosyl)urea and 5.0V of nitrogen tetroxide gas were treated in the same manner as in Example 31-(2), 1-(2-chloroethyl)-1-nitroso3-
Furfuryl-3-(D-ribopyranosyl)urea 2.2y
is obtained as a yellow powder.

M. P. 6TC (disassembly) IRv 01 (C77!-1): 3450, 1700
11070, 1040, 1010NMR (D2O
) δ: 6.39 (M, 2H, [α] V - 2.8 δ (C =
0. g. Methanol) Example 37 (1) D-xylose 3.0y1 cyclopropylmethylamine 2.2y and 2-chloroethyl isocyanate 2.5y Example 31
- Treated in the same manner as in (1) to produce 1-(2-chloroethyl)
3.8 g of -3-cyclopropylmethyl-3-(D-xylopyranosyl)urea are obtained as colorless caramel.

Shaku ν to 01 (c1-Rini 335 to 1? to 153 to 10
50NMR (D2O) δ: 0.20-0.68 (M, 4
H, 4.98 (D, lH, Cl-H) (2) 1-(2-
chloroethyl)-3-cyclopropylmethyl-3-(D
-xylopyranosyl) urea 3.1y and nitrogen tetroxide gas 5y were treated in the same manner as in Example 31-(2), and 1-
(2-chloroethyl)-1-nitroso-3-cyclopropylmethyl-3-(D-xylopyranosyl)urea 2.2
' is obtained as a yellow caramel.

4?13 (d-1): (...0, 1080N to 170
MR (D2O) δ: 0.20-0.70 (M, 4H,)
4.18(T,2H,-N(NO)CJlI,CH2C
l) [α]t+11.0, (C=1.5.methanol)
Example Feather (1) D-glucose 3.6f1 Tetrahydrofurfurylamine 4.0f1 and 2-chloroethyl isocyanate 2.5y were treated in the same manner as in Example 31-(1) to obtain 1-(2-chloroethyl)- 3-Tetrahydrofurfuryl-3-(D-glucopyranosyl)urea5.
2y is obtained as a colorless caramel.

R'' (spoon 01 (c!n-Rini 335 to 1 trouble to 1M to 10
70NMR (D2O) δ: 1.50-2.16 (M, 4
H, 5.04 (D, lH, Cl-H) (2) 1-(2-
chloroethyl)-3-tetrahydrofurfuryru-3-(
3.7y of D-glucopyranosyl) urea and 6y of nitrogen tetroxide gas were treated in the same manner as in Example 31-(2) to obtain 1
-(2-chloroethyl)-1-nitroso-3-tetrahydrofurfuryl-3-(D-glucopyranosyl)urea 1
．． 1y is obtained as a yellow caramel.

■Rp: Shima 13 (Cr!t-1): 169\1 to 340
070NMR (D2O) δ: 1.56-2.10 (M,
4H,4.2O(T,2H-N(NO)Cdan,1)4.
96 (D, lH, Cl-H) [α]? +21.6, (C
=1. Hemethanol) Example 39 (1) D-mannose 3.6y1 cyclopropylmethylamine 2.2f and 2-chloroethyl isocyanate 2.5y in Example 31
- Treated in the same manner as in (1) to produce 1-(2-chloroethyl)
-3-Cyclopropylmethyl-3-(D-mannopyranosyl)urea 4.3f1 is obtained as a colorless caramel.

1Rp: Spoon 01 (d-1): 3350, 1530 to 18
, 1060NMR (D2O) δ: 0.20-0.72(
M,. Example 31-(
2) to give 1-(2-chloroethyl)-1
-Nitroso-3-cyclopropylmethyl-3-(D-mannopyranosyl)urea 2.3y is obtained as a yellow caramel.

IRp:? 13 (Cwl-1): 169α1μ to 340
SONMR (D2O) δ: 0.20-0.68 (M, 4
H, [α]e+26.3: (C=1.3, methanol)
Example 40 3.7y of 1-(2-chloroethyl)-3-tetrahydrobufurfuryl-3-(-D-galactopyranosyl)urea was dissolved in 15mt of formic acid, and 2.1f of sodium nitrite was added thereto with stirring. Add gradually over 1 hour at 0°C.

This mixture was further stirred three times at the same temperature, and a mixed solution of ether-hexane (1:S1) was added. The precipitated oil was washed with ether and diluted with ethyl acetate-methanol (10:
1) Add 100ml of the mixed liquid. Insoluble matters are removed by filtration, the filtrate is concentrated, and the solvent is distilled off. The obtained residue was purified by silica gel chromatography (solvent: ethyl acetate-chloroform-methanol) (5:2:1). 1-(2-chloroethyl)-1-nitroso-3-tetrahydrofurfuryl-3-
(D-galactopyranosyl)urea 0.9f is obtained as yellow caramel.

[α]♂+16.6 la (C=1.2, methanol) Example 411-(2-chloroethyl)-3-cyclopropylmethyl-3-(L-arabinopyranosyl) urea 3.1y
Dilute with 15 ml of formic acid and add 1.5 ml of sodium nitrite to this.
Add y gradually over a period of 1 hour at 0° C. with stirring.

This mixture is further stirred at the same temperature for 1 hour. After the reaction, 15 ml of ethanol was added to the reaction solution, and then cooled on ice.
Neutralize with potassium carbonate. Add 150ml of ethyl acetate to this
was added, insoluble matter was filtered off, the filtrate was washed with hydrogenated sodium chloride water, dried, concentrated, and the solvent was distilled off. The residue thus obtained is purified by silica gel chromatography (solvent: ethyl acetate-chloroform-methanol (5:2:1)). 1-(
2-chloroethyl)-1-nitroso-3-cyclopropylmethyl-3-(L-arabinopyranosyl)urea 1.5
y is obtained as a yellow caramel.

[α]? +54.7y (C=1.2, methanol) Example 42 1-(2-chloroethyl)-3-cyclopropylmethyl-3-(D-ribopyranosyl)urea and 1.5f of sodium nitrite were added in the same manner as in Example 41. Process, 1
-(2-chloroethyl)-1-nitroso-3-cyclopropylmethyl-3-(D-ribopyranosyl)urea 1.6
fI is obtained as a yellow powder.

Claims (1)

[Claims] 1 General formula▲ Numerical formulas, chemical formulas, tables, etc.▼[I] (However, in the formula, R^1 is an alicyclic group having 3 to 6 carbon atoms; phenyl group; halogen; carbon number 1) -4 lower alkyl group, lower alkoxy group having 1 to 4 carbon atoms, phenyl group having 1 to 3 substituents selected from the group consisting of hydroxyl group and nitro group; or oxiranyl group, tetrahydrofuryl group, 1,3- Represents a heteromonocyclic group selected from the group consisting of dioxolanyl group, 1,4-dioxanyl group, morpholino group, tetrahydro-S,S-dioxo-chenyl group, furyl group, chenyl group, and pyridyl group, and R^2 is Aldo-pentopyranosyl group, aldo-hexopyranosyl group or O-
Aldo-hexopyranosyl-(1→4)-aldo-hexopyranosyl group, A is a single bond or has 1 to 3 carbon atoms
represents a straight chain or branched alkylene group. ) Nitrosourea derivatives. 2 In the general formula [I], R^2 is a D or L-aldo-pentopyranosyl group, a D or L-aldo-hexopyranosyl group, or an O-D-aldo-hexopyranosyl-(1→4)-D-aldo-hexopyranosyl group A compound according to claim 1. 3 General formula ▲ Numerical formula, chemical formula, table, etc. ▼ [II] (However, in the formula, R^1 is an alicyclic group having 3 to 6 carbon atoms; phenyl group; halogen; lower alkyl group having 1 to 4 carbon atoms. , a phenyl group having 1 to 3 substituents selected from the group consisting of a lower alkoxy group having 1 to 4 carbon atoms, a hydroxyl group, and a nitro group; or an oxiranyl group, a tetrahydrofuryl group, a 1,3-dioxolanyl group, a 1,4 - Represents a heteromonocyclic group selected from the group consisting of dioxanyl group, morpholino group, tetrahydro-S,S-dioxo-chenyl group, furyl group, chenyl group, and pyridyl group, and R^2 represents an aldo-pentopyranosyl group, an aldo-pentopyranosyl group, an aldo -hexopyranosyl group or O-aldo-hexopyranosyl-(1→4)-aldo-hexopyranosyl group, A represents a single bond or a straight chain or branched alkylene group having 1 to 3 carbon atoms. General formulas characterized by nitrosation▲There are mathematical formulas, chemical formulas, tables, etc.▼〔I〕(However,
R^1, R^2 and A have the same meanings as above. ) A method for producing a nitrosourea derivative. 4 General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [II'] (However, R
^2 is aldo-pentopyranosyl group, aldo-hexopyranosyl group or O-aldo-hexopyranosyl-(
1→4)-Aldo-hexopyranosyl group, and A represents a single bond or a straight chain or branched alkylene group having 1 to 3 carbon atoms. ) is nitrosated to obtain a nitrosourea derivative represented by the general formula ▲ Numerical formula, chemical formula, table, etc. ▼ [III] (However, R^2 and has the same meaning as above.) There are general formulas ▲ mathematical formulas, chemical formulas, tables, etc. that are characterized by epoxidizing this nitrosourea derivative represented by [I ′] (However, R^2 and A have the same meanings as above.) Manufacturing method.