The epoxysuccinic acid derivatives of this invention are prepared by esterification of an epoxysuccinic acid or a halide thereof, by partial hydrolysis of an epoxysuccinic acid diester, by amidation of an epoxysuccinic acid monoester, or by hydrolysis of an epoxysuccinic acid amide monoester. These epoxysuccinic acid derivatives have excellent thiol protease inhibitory activity and anti-inflammatory activity without the acceleration of vascular permeability.

BACKGROUND 
Prior to the present invention, E-64 has been the only known epoxysuccinic 
acid compound possessing thiol protease inhibitory activity together with 
anti-inflammatory activity as described in U.S. Pat. No. 3,911,111. This 
compound, however, has an undesirable side effect, i.e., the acceleration 
of vascular permeability. 
The novel epoxysuccinic acid derivatives of the present invention are 
distinguished from the prior art patented compound by their excellent 
thiol protease inhibitory activity and anti-inflammatory activity and by 
the absence of the acceleration of vascular permeability as shown in tests 
upon laboratory animals. 
DESCRIPTION AND PREFERRED EMBODIMENTS 
This invention relates to a novel trans epoxysuccinic acid derivative 
represented by the general formula 
##STR1## 
wherein 
(1) R.sup.1 and R.sup.2 are each R.sup.3 wherein R.sup.3 is --O--A.sup.1 
--R.sup.4, --O--A.sup.2 --R.sup.5 or --OCH.sub.2 --R.sup.6 wherein A.sup.1 
is alkylene containing zero to 4 carbon atoms or said alkylene substituted 
with methyl, R.sup.4 is cycloalkyl containing 3 to 10 carbon atoms, or 
said cycloalkyl substituted with one to 3 halogen or methyl, A.sup.2 is 
alkylene containing 2 or 3 carbon atoms or alkenylene containing 2 or 3 
carbon atoms, R.sup.5 is phenyl, R.sup.6 is furyl, tetrahydrofuryl, 
thienyl, naphthyl, naphthyl substituted with one or two halogens or 
methyl, or phenyl substituted with one to three halogen, methyl, methoxy, 
methylenedioxy or trifluoromethyl groups, or cycloalkenyl containing 5 to 
8 carbon atoms, or 
(2) R.sup.1 is hydroxy, R.sup.3 or R.sup.7, and R.sup.2 is hydroxy or 
R.sup.8 wherein R.sup.3 is as defined above, R.sup.7 is alkoxy containing 
one to 12 carbon atoms, allyloxy, propargyloxy, phenoxy or benzyloxy, and 
R.sup.8 is an amino acid residue represented by the general formula 
EQU --NH--A.sup.3 --COR.sup.9 
wherein A.sup.3 is methylene, ethylene, trimethylene, alkylidene containing 
2 to 5 carbon atoms or said alkylides substituted with one to 3 hydroxy, 
methyl, thiol, methylthio, benzylthio, phenyl, phenyl substituted with 
hydroxy or halogen, indazolyl, imidazolyl, --COR.sup.10 or --NHR.sup.11 
wherein R.sup.10 is amino or --OR.sup.12 wherein R.sup.12 is hydrogen, 
alkyl containing one to 5 carbon atoms, benzyl or an alkali metal cation, 
and R.sup.11 is hydrogen, formyl, alkoxycarbonyl containing 2 to 5 carbon 
atoms, benzyloxycarbonyl, methoxybenzyloxycarbonyl, tosyl, guanyl, or 
guanyl substituted by nitro, and R.sup.9 is amino or --OR.sup.13 is 
hydrogen, alkyl containing one to 5 carbon atoms, benzyl or an alkali 
metal cation with the proviso that R.sup.1 is neither hydroxy, alkoxy 
containing one to 12 carbon atoms, nor phenoxy when R.sup.2 is hydroxy, 
and salts thereof when R.sup.1 or R.sup.2 is hydroxy. 
In this specification and claims, unless otherwise noted, the term 
"halogen" or "halo" refers to chloro, bromo, iodo and fluoro, and the 
epoxysuccinic acid derivatives are limited to the trans isomers, namely, 
the two carbonyl groups on the oxirane ring are in trans configuration 
each other. 
With regard to the compound of this invention, examples of --O--A.sup.1 
--R.sup.4 are --O--R.sup.4, --OCH.sub.2 --R.sup.4, --O--(CH.sub.2).sub.2 
--R.sup.4, --O--(CH.sub.2).sub.3 --R.sup.4, and --O--(CH.sub.2).sub.4 
--R.sup.4. Examples of the alkylene substituted with methyl in A.sup.1 are 
methylmethylene, 1- or 2-methylethylene, 1-, 2- or 3-methylpropylene, or 
1-, 2-, 3- or 4-methylbutylene. Examples of the cycloalkyl containing 3 to 
10 carbon atoms in R.sup.4 are cyclopropyl, cyclobutyl, cyclopentyl, 
cyclohexyl, cycloheptyl, bicycloheptyl, cyclooctyl, bicyclooctyl, 
adamantyl, and the like. The substituent on the cycloalkyl in R.sup.4 may 
be on any position, and when 2 or 3 substituents are present, they are the 
same or different. Examples of the cycloalkenyl in R.sup.6 are 
cyclopentenyl, cyclohexenyl, bicycloheptenyl, cyclooctenyl and the like. 
Examples of --O--A.sup.2 --R.sup.5 are 2-phenylethyloxy, 
3-phenylpropyloxy, cinnamyloxy, styryloxy and the like. Each substituent 
on naphthyl and phenyl in R.sup.6 may independently be on any position, 
and when 2 or 3 substituents are present, they may be the same or 
different. Examples of the alkoxy containing one to 12 carbon atoms in 
R.sup.7 are methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, 
heptyloxy, octyloxy, nonyloxy, decyloxy, undecyloxy, dodecyloxy and 
isomeric forms thereof. 
The substituent on the alkylene in A.sup.3 may be on any position, and when 
2 or 3 substituents are present, they are the same or different. The 
substituent on phenyl attached to the alkylene in A.sup.3 may be on any 
position, and when two or three substituents are present, they may be the 
same or different. Examples of the alkali metal cations in R.sup.12 or 
R.sup.13 are independently potassium or sodium. Examples of the amino acid 
corresponding to said amino acid residue are glycine, .alpha.- or 
.beta.-alanine, valine, leucine, serine, threonine, methionine, 
phenylalanine, tyrosine, cysteine, asparagine, glutamine, histidine, 
tryptophan, aspartic acid, lysine, glutamic acid, hydroxylysine, arginine, 
ornithine, .gamma.-amino butylic acid and the like, and those with a 
suitable protective group. 
The salts of the compound(I) wherein R.sup.1 or R.sup.2 is hydroxy, are 
those with alkali metal cations such as potassium and sodium. 
In a preferred embodiment of this invention, epoxysuccinic acid derivatives 
of this invention may be prepared by the following reaction sequence. 
##STR2## 
In this reaction sequence, R.sup.14 is hydroxy or halogen, R.sup.15 is 
R.sup.3 or R.sup.7, R.sup.16 and R.sup.17 are independently hydrogen or 
alkali metal cation, X is halogen, and R.sup.8 is as defined above. The 
starting material(II) wherein R.sup.14 is halogen may be dissolved in an 
organic solvent such as ethyl ether, benzene and cyclohexane. To the 
resulting solution, R.sup.15 H may be added along with an organic base 
such as triethylamine, pyridine and methylmorphorine to give the 
epoxysuccinic acid diester(III). Also, to the starting material(II) 
wherein R.sup.14 is hydroxy in the same organic solvent as described 
above, R.sup.15 H may be added in the presence of an acid catalyst such as 
sulfuric acid to give the epoxysuccinic acid diester(III). 
The epoxysuccinic acid diester(III) thus obtained may be dissolved in an 
organic solvent or a mixture of the organic solvent and water. Examples of 
said organic solvent are dioxane, acetone, tetrahydrofuran, 
dimethylformamide, dimethylsulfoxide, and alcohols such as ethanol, 
methanol and R.sup.15 H. To the resulting solution, a caustic alkali such 
as potassium hydroxide, sodium hydroxide or the like in the same solvent 
as described above or water may be added with ice-cooling or at room 
temperature. Equimolecular quantities of the caustic alkali have to be 
used in this reaction. The resulting mixture may be stirred for 5 to 120 
minutes, and then, if necessary, followed by addition of acetone, dioxane, 
ethyl ether or petroleum ether to give the compound(IV) wherein R.sup.16 
is an alkali metal cation. The compound(IV) wherein R.sup.16 is alkali 
metal cation may be acidified with an inorganic acid such as sulfuric 
acid, hydrochloric acid and the like, and extracted with an organic 
solvent such as ethyl acetate or benzene to give the compound(IV) wherein 
R.sup.16 is hydrogen. 
The compound(IV) wherein R.sup.16 is hydrogen or alkali metal cation may be 
dissolved in an organic solvent such as ethyl ether, benzene, cyclohexane, 
dimethylformamide, dichloromethane and the like, and then treated with a 
halogenating agent such as oxalyl chloride to give the compound(V). The 
compound(V) thus obtained, may be dissolved in an organic solvent such as 
benzene, ethyl ether or dichloromethane together with an organic base such 
as triethylamine, pyridine, methylmorphorine or the like with ice-cooling 
or room temperature to give the compound(VI). 
In another method, the compound(IV) wherein R.sup.16 is hydrogen may be 
dissolved in an organic solvent such as ethyl ether, benzene, cyclohexane, 
dimethylformamide, dichloromethane, tetrahydrofuran and the like, and then 
reacted with R.sup.8 H in the presence of a condensing agent such as 
dicyclohexylcarbodiimide and/or in the presence of hydroxysuccinoimide or 
1-hydroxybenzotiazole to give the compound(VI). 
The compound(VI) thus obtained may be dissolved in water, an organic 
solvent such as ethanol, benzylalcohol, dioxane, ethyl ether and the like, 
or in a mixture of water and the organic solvent. The resulting solution 
may be reacted with the equimolar of a caustic alkali such as potassium 
hydroxide, sodium hydroxide and the like in the same solvent as described 
above with ice-cooling or at room temperature. The resulting mixture may 
be stirred for 5 to 120 minutes, and then, if necessary, followed by 
addition of ethanol, acetone, dioxane, ethyl ether or petroleum ether to 
give the alkali metal salt of the compound(VII). If desired, the 
protecting groups attached to carbonyl in R.sup.8 of the compounds(VI) or 
(VII) may be removed by the addition of an excess amount of said caustic 
alkali. 
The alkali metal salt obtained may be collected by filtration, and purified 
by washing or recrystallization. The salt may be acidified with an 
inorganic acid such as sulfuric acid, and extracted with an organic 
solvent such as ethyl acetate or benzene to give the free acid. 
If desired, the protecting groups attached to amino or carboxyl in R.sup.8 
of the compound(VI) or (VII) may be removed by catalytic reduction using 
palladium carbon or palladium black. 
The starting material(II) wherein R.sup.14 is hydroxy can be prepared by 
the method as described in Journal of Organic Chemistry, 24, 54(1959), and 
the starting material(II) wherein R.sup.14 is halogen can be prepared by 
the method as described in Journal of Medical Chemistry, 6, 233(1963), or 
by that with some modification. Furthermore, R.sup.3 H, R.sup.7 H and 
R.sup.8 H are to a large extent commercially available. 
The compounds of this invention inhibit effectively and specifically thiol 
proteases such as papain, bromelains and some kinds of cathepsin in which 
some sulfhydryl groups are essential for activity. On the other hand, the 
compounds of this invention, have no inhibitory activity against 
proteolysis of casein by trypsin, chymotrypsin, pepsin, acid protease of 
Peacilomyces varioti or Nagarse (trademark of Nagase Industry), 
esterolysis of benzoylarginine ethyl ester by kallikrein, or against 
fibrinolysis by human plasmin. 
Papain inhibitory activity of the compounds of this invention was assayed 
as follows: To 0.5 ml of a solution of papain (80 .mu.g/ml, Sigma Chem. 
Co., 2x cry.), were added 0.25 ml of 40 mM cysteine dissolved in 20 mM 
disodium ethylenediamine tetraacetic acid solution adjusted pH to 6.8 with 
sodium hydroxide and 0.25 ml of 33 mM phosphate buffer (pH 6.8) with or 
without inhibitor. After incubation at 40.degree. C. for 15 minutes, the 
resulting mixture was added to 5 ml of 1% milk casein solution in the same 
buffer as described above, and further incubated at 40.degree. C. for 10 
minutes. Then the mixture was mixed with 5 ml of 0.44 M trichloroacetic 
acid solution and followed by filtration with a sheet of Toyo filter paper 
No. 4. The extinction of the filtrate was read at 280 nm. The percent 
inhibition was calculated from the formula, 100 x (B-A)/B; wherein B 
stands for the absorbance without inhibitor and A for the absorbance with 
inhibitor. The amount of inhibitor for 50% inhibition was expressed as 
ID.sub.50, and shown in Table 1. The compound Nos. in Table 1 are as 
defined in Examples as described hereinafter. 
TABLE 1 
______________________________________ 
Com- Com- Com- 
pound pound pound 
No. ID.sub.50 (.gamma.) 
No. ID.sub.50 (.gamma.) 
No. ID.sub.50 (.gamma.) 
______________________________________ 
EP - 1 1.98 EP - 35 0.98 EP - 69 
0.23 
2 0.07 
36 0.07 
70 0.08 
3 2.12 
37 0.22 
71 0.40 
4 0.09 
38 0.06 
72 0.08 
5 2.36 
39 4.39 
73 0.10 
6 0.09 
40 0.34 
74 0.07 
7 2.25 
41 0.27 
75 1.65 
8 0.07 
42 0.06 
76 0.82 
9 2.20 
43 0.45 
77 0.77 
10 0.06 
44 0.07 
78 0.54 
11 2.50 
45 0.23 
79 0.75 
12 0.07 
46 0.08 
80 0.32 
13 2.50 
47 0.25 
81 1.30 
14 0.10 
48 0.08 
82 0.34 
15 1.69 
49 0.85 
83 1.55 
16 0.08 
50 0.09 
84 0.29 
17 1.79 
51 0.30 
85 1.56 
18 0.08 
52 0.07 
86 0.27 
19 2.01 
53 0.45 
87 1.58 
20 0.06 
54 0.09 
88 0.32 
21 2.46 
55 0.28 
89 1.39 
22 0.12 
56 0.06 
90 0.25 
23 2.45 
57 0.26 
91 0.35 
24 0.09 
58 0.07 
92 0.10 
25 3.03 
59 0.18 
93 4.31 
26 0.08 
60 0.10 
94 0.27 
27 20.00 
61 1.18 
95 4.20 
28 0.80 
62 0.08 
96 0.37 
29 3.12 
63 54.82 
97 3.20 
30 0.07 
64 0.10 
98 0.32 
31 3.25 
65 69.44 
99 0.50 
32 0.09 
66 0.08 
100 0.10 
33 3.20 
67 93.28 
101 1.51 
34 0.07 
68 0.10 
102 0.36 
103 1.06 
137 2.08 
171 5.80 
104 0.36 
138 0.82 
172 6.20 
105 0.40 
139 0.78 
173 5.80 
106 0.14 
140 0.92 
174 0.20 
107 0.15 
141 1.45 
175 1.90 
108 0.09 
142 0.29 
176 1.06 
109 0.50 
143 0.15 
177 1.50 
110 0.24 
144 0.34 
178 4.63 
111 2.91 
145 0.14 
179 1.60 
112 0.32 
146 0.39 
180 9.76 
113 0.99 
147 3.40 
181 6.59 
114 0.26 
148 0.70 
182 5.95 
115 1.20 
149 0.70 
183 4.46 
116 0.32 
150 3.10 
184 2.91 
117 2.55 
151 7.20 
185 14.05 
118 0.11 
152 48.20 
186 23.15 
119 3.00 
153 17.90 
187 1.40 
120 0.40 
154 43.90 
188 1.86 
121 0.46 
155 9.20 
189 10.58 
122 0.10 
156 13.80 
190 17.13 
123 0.30 
157 71.50 
191 5.51 
124 0.10 
158 3.47 
192 40.50 
125 2.90 
159 0.27 
193 20.50 
126 0.12 
160 0.30 
194 22.60 
127 2.00 
161 3.40 
195 0.43 
128 0.11 
162 0.80 
196 0.11 
129 0.78 
163 29.07 
197 0.98 
130 0.10 
164 20.49 
198 0.15 
131 11.36 
165 22.50 
199 0.14 
132 0.17 
166 0.67 
200 0.88 
133 2.81 
167 0.50 
201 25.51 
134 0.71 
168 12.50 
202 21.93 
135 12.20 
169 26.50 
203 0.12 
136 2.72 
170 27.50 
204 15.20 
EP - 205 
0.82 
206 0.12 
207 6.52 
208 13.12 
209 2.45 
210 1.12 
211 0.61 
212 1.21 
213 6.75 
214 0.13 
215 3.55 
216 3.25 
217 0.25 
218 1.65 
219 2.12 
220 9.86 
______________________________________ 
The compounds of this invention also show marked anti-inflammatory activity 
as measured by their ability to inhibit adjuvant induced polyarthritis in 
rats. Effect of the compounds of this invention on the development of 
adjuvant-induced polyarthritis in rats was assayed as follows: Adjuvant 
arthritis was produced by a single intracutaneous injection of 0.1 ml of 
the adjuvant mixture containing heat-killed mycobacteria of the human 
Aoyama B strain suspended in liquid paraffin in 0.6% in the middle part of 
the distal tail of Sprague Dawley rat (female, 8 weeks old). The compounds 
suspended in 0.5% carboxymethylcellulose solution protected the animal 
against the development of lession of adjuvant arthritis by daily oral 
administration beginning on the day of adjuvant injection and continuing 
for 24 days thereafter. The activity was measured as the mean inhibition 
percent for the increase of the hind paw volume of the 8 rats/group on the 
days 17 and 23 on which the legs become inflamed and reach maximum 
volumes. The results are shown in Table 2. The compound Nos. in Table 2 
are as defined in Examples as described hereinafter. 
TABLE 2 
______________________________________ 
Compound Dose (mg/kg of Inhibition % 
No. body weight) 17 days 23 days 
______________________________________ 
EP - 1 100 82.1 77.0 
2 100 43.2 50.0 
17 100 100.0 78.7 
25 100 52.6 77.8 
26 100 52.0 55.5 
75 100 89.6 41.0 
79 100 64.3 90.2 
81 100 64.3 83.6 
102 100 28.0 31.0 
116 100 35.0 33.5 
121 100 53.6 38.9 
131 100 57.1 49.2 
137 100 40.0 38.5 
143 100 45.1 35.6 
144 100 33.3 32.1 
174 100 30.5 29.0 
175 100 32.0 31.5 
______________________________________ 
The pharmaceutical forms contemplated by this invention include 
pharmaceutical compositions suited for oral, parenteral, and rectal use, 
e.g., tablets, powder packets, cachets, dragees, capsules, solutions, 
suspensions, sterile injectable forms, supporsitories, bougies, and the 
like. The carrier employed may be, for example, either a solid or liquid. 
Examples of solid carriers are lactose, terra alba, sucrose, talc, 
gelatin, agar, pectin, acacia, magnesium stearate, stearic acid and the 
like. Examples of liquid carriers are syrup, peanut oil, olive oil, water 
and the like. Similarly, the carrier or diluent can include any time delay 
material well known to the art, such as glyceryl monostearate or glyceryl 
distearate alone or with a wax. 
The compounds of this invention can be used as anti-inflammatory agents in 
dosages of 10-700 mg/kg, prefarably 20-100 mg/kg in oral or injectable 
preparations as described above, to protect mammals against the 
development of arthritis. 
The compounds of this invention are of extremely low toxicity. That is, 
they hardly show any oral acute toxicity on mice at a dose less than 2 
g/kg of body weight. Moreover, no side effect is observed after 
administration of 1 g/kg/day orally for 30 days for laboratory animals. 
The following examples are illustrative of the present invention and are 
not intended in any way to limit the invention, the scope of which is 
defined by the appended claims.

EXAMPLE 1 
To a solution of 3.0 g (0.026 mole) of cyclohexanol and 2.1 g (0.026 mole) 
of pyridine dissolved in 50 ml of ethyl ether, a solution of 2.52 g (0.015 
mole) of epoxysuccinyl chloride dissolved in 5 ml of ethyl ether was added 
dropwise while being stirred and cooled at 0.degree. to -5.degree. C. 
After the mixture had been stirred for 30 to 60 min., the precipitated 
hydrogen chloride salt of pyridine was filtered out. The ethyl ether layer 
thus obtained was washed with water, dried over anhydrous sodium sulfate 
and distilled to dryness. The resulting residue was chromatographed on 
silica gel using n-hexane-acetone (10:1) mixture as solvent to give 
dicyclohexyl epoxysuccinate (EP-1) as an oil. Yield 3.3 g (75%), b.p. 
225.degree.-227.degree. C. (6 mmHg). 
EXAMPLE 2 
(a) To a solution of 2.5 g (0.0085 mole) of dicyclohexyl epoxysuccinate 
dissolved in 40 ml of cyclohexanol, a solution of 0.4 g of potassium 
hydroxide dissolved in 3 ml of methanol was added dropwise at room 
temperature. After the mixture had been stirred for 2 hours, to this, 300 
ml of ethyl ether was added. Then, the mixture was allowed to stand 
overnight at about 5.degree. C. The precipitate thus formed was filtered 
and recrystallized from ethanol-ether mixture to give cyclohexyl potassium 
epoxysuccinate (EP-2) as colorless needles. Yield 1.2 g (48%), m.p. 
187.degree.-189.degree. C. 
(b) To a solution of 1.0 g (0.0034 mole) of dicyclohexyl epoxysuccinate 
dissolved in 30 ml of dimethylformamide, 2 ml of aqueous 1 N potassium 
hydroxide solution was added dropwise while being stirred and cooled at 
0.degree. C. After 10 min., the mixture was filtered. Then, to the 
solution, 400 ml of acetone was added and the mixture was allowed to stand 
for a while. The resulting crystals were recrystallized from water-acetone 
to give cyclohexyl potassium epoxysuccinate (EP-2) as colorless needles. 
Yield 0.74 g (74%), m.p. 188.degree.-190.degree. C. 
EXAMPLE 3 
To a solution of 3.0 g (0.026 mole) of 2-cis-methylcyclohexanol, and 2.1 g 
(0.026 mole) of pyridine dissolved in 50 ml of ethyl ether, a solution of 
2.52 g (0.015 mole) of epoxysuccinyl chloride dissolved in 5 ml of ethyl 
ether was added dropwise while being stirred and cooled at 0.degree. to 
-5.degree. C. After the mixture had been stirred for 30 to 60 min., the 
precipitated hydrogen chloride salt of pyridine was filtered out. The 
ethyl ether layer thus obtained was washed with water, dried over 
anhydrous sodium sulfate and distilled to dryness. The resulting residue 
was chromatographed on silica gel using n-hexaneacetone (10:1) mixture as 
solvent to give di-2'-cis-methylcyclohexyl epoxysuccinate (EP-3) as an 
oil. Yield 3.3 g (77%). IR.nu..sub.KBr (cm.sup.-1): 1740 (ester,carbonyl), 
900 (epoxide). NMR(CDCl.sub.3).delta.: 0.87 (6H,d,J=6 Hz), 1.10-2.00 (18H, 
b.s.), 3.61 (2H, s), 5.00 (2H,b.s.). 
The following compounds were obtained from the corresponding materials by 
method similar to that described in Example 3. 
di-2'-trans-methylcyclohexyl epoxysuccinate(EP-5), 
di-2'-trans-chlorocyclohexyl epoxysuccinate(EP-7), 
di-3'-cis-bromocyclohexyl epoxysuccinate(EP-9), 
di-2'-cis-bromo-5'-trans-chlorocyclohexyl epoxysuccinate(EP-11), 
di-2',6'-trans-dimethylcyclohexyl epoxysuccinate(EP-13) 
EXAMPLE 4 
To a solution of 5.0 g (0.016 mole) of di-2'-cis-methylcyclohexyl 
epoxysuccinate dissolved in 50 ml of dimethylformamide, 5.14 ml of aqueous 
3 N potassium hydroxide solution was added dropwise while being stirred 
and cooled at 0.degree. C. After the mixture had been stirred for 10 to 15 
min., to this, 1000 ml of acetone was added. The formed crystals were 
filtered and recrystallized from acetone-water to give 
2'-cis-methylcyclohexyl potassium epoxysuccinate(EP-4) as colorless 
crystals. Yield 0.6 g (15%), m.p.&gt;300.degree. C.(d.). IR.nu..sub.KBr 
(cm.sup.-1): 1740 (ester, carbonyl), 1620 (COOK), 900 (epoxide). 
NMR(D.sub.2 O).delta.: 1.20-2.25 (9H, m), 2.26 (3H, s), 3.45, 3.55 (2H, 
d.d., J=2 Hz), 4.95 (1H,m). 
The following compounds were obtained from the corresponding materials by 
methods similar to that described in Example 4. 
2'-trans-methylcyclohexyl potassium epoxysuccinate(EP-6), 
2'-trans-chlorocyclohexyl potassium epoxysuccinate(EP-8), 
3'-cis-bromocyclohexyl potassium epoxysuccinate(EP-10), 
2'-cis-bromo-5'-trans-chlorocyclohexyl potassium epoxysuccinate(EP-12), 
2',6'-trans-dimethylcyclohexyl potassium epoxysuccinate(EP-14). 
EXAMPLE 5 
To a solution of 3.0 g (0.026 mole) of 4-trans-methylcyclohexanol and 2.1 g 
(0.026 mole) of pyridine dissolved in 50 ml of ethyl ether, a solution of 
2.52 g (0.015 mole) of epoxysuccinyl chloride dissolved in 5 ml of ethyl 
ether was added dropwise while being stirred and cooled at 0.degree. to 
-5.degree. C. After the mixture had been stirred for 30 to 60 min., the 
precipitated hydrogen chloride salt of pyridine was filtered out. The 
ethyl ether layer thus obtained was washed with water, dried over 
anhydrous sodium sulfate and distilled to dryness. The resulting residue 
was chromatographed on silica gel using n-hexane-acetone (10:1) mixture as 
solvent to give di-4'-trans-methylcyclohexyl epoxysuccinate(EP-15) as an 
oil. Yield 3.8 g (88%). IR.nu..sub.KBr (cm.sup.-1): 1745 (ester, 
carbonyl), 900 (epoxide). NMR(CDCl.sub.3).delta.: 0.88 (6H, b.s.), 
1.00-2.16 (18H, m), 3.52 (2 H, s), 4.69 (2H, b.s.). 
The following compounds were obtained from the corresponding materials by 
methods similar to that described in Example 5. 
di-4'-cis-methylcyclohexyl epoxysuccinate(EP-17), 
di-4'-trans-chlorocyclohexyl epoxysuccinate(EP-19), 
di-3'-cis-chloro-trans-4'-bromocyclohexyl epoxysuccinate(EP-21), 
di-3',5'-trans-dichlorocyclohexyl epoxysuccinate(EP-23). 
EXAMPLE 6 
To a solution of 5.0 g (0.016 mole) of di-4'-trans-methylcyclohexyl 
epoxysuccinate dissolved in 50 ml of dimethylformamide, 5.14 ml of aqueous 
3 N potassium hydroxide solution was added dropwise while being stirred 
and cooled at 0.degree. C. After the mixture had been stirred for 10 to 15 
min., to this, 1000 ml of acetone was added. The formed crystals were 
filtered and recrystallized from acetone-water to give 
4'-trans-methylcyclohexyl potassium epoxysuccinate(EP-16) as colorless 
crystals. Yield 0.7 g (17%), m.p.&gt;300.degree. C.(d.). IR.nu..sub.KBr 
(cm.sup.-1): 1745 (ester, carbonyl), 1618 (COOK), 902 (epoxide). NMR 
(D.sub.2 O).delta.: 1.0-2.3 (9H, m), 2.25 (3H, s), 3.40, 3.51 (2H, d.d., 
J=2 Hz), 4.76 (1H, m). 
The following compounds were obtained from the corrsponding materials by 
methods similar to that described in Example 6. 
4'-cis-methylcyclohexyl potassium epoxysuccinate(EP-18), 
4'-trans-chlorocyclohexyl potassium epoxysuccinate(EP-20), 
3'-cis-chloro-4'-trans-bromocyclohexyl potassium epoxysuccinate(EP-22), 
3',5'-trans-dichlorocyclohexyl potassium epoxysuccinate(EP-24). 
EXAMPLE 7 
To a solution of 3.0 g (0.026 mole) of cyclopentanol and 2.1 g (0.026 mole) 
of pyridine dissolved in 50 ml of ethyl ether, a solution of 2.52 g (0.015 
mole) of epoxysuccinyl chloride dissolved in 5 ml of ethyl ether was added 
dropwise while being stirred and cooled at 0.degree. to -5.degree. C. 
After the mixture had been stirred for 30 to 60 min., the precipitated 
hydrogen chloride salt of pyridine was filtered out. The ethyl ether layer 
thus obtained was washed with water, dried over anhydrous sodium sulfate 
and distilled to dryness. The resulting residue was chromatographed on 
silica gel using n-hexane-acetone (10:1) mixture as solvent to give 
dicyclopentyl epoxysuccinate(EP-25) as an oil. Yield 3.6 g (77%), b.p. 
221.degree.-223.degree. C. (6 mmHg). 
The following compound was obtained from the corresponding material by 
methods similar to that described in Example 7. 
dicyclopropyl epoxysuccinate(EP-27). 
EXAMPLE 8 
(a) When a procedure as described in Example 2(a) was carried out by using 
dicyclopentyl epoxysuccinate (2.5 g) and cyclopentanol (40 ml) instead of 
dicyclohexyl epoxysuccinate and cyclohexanol, respectively, cyclopentyl 
potassium epoxysuccinate(EP-26) was obtained as crystals. Yield 1.2 g 
(48%), m.p. 157.degree.-160.degree. C. (from water-acetone). 
(b) When a procedure as described in Example 2(b) was carried out by using 
dicyclopentyl epoxysuccinate (1.0 g) instead of dicyclohexyl 
epoxysuccinate, cyclopentyl potassium epoxysuccinate(EP-26) was obtained 
as crystals. Yield 0.68 g (68%), m.p. 157.degree.-160.degree. C. (from 
water-acetone). 
The following compound was obtained from the corresponding material by a 
method as described in Example 8(b). 
cyclopropyl potassium epoxysuccinate(EP-28). 
EXAMPLE 9 
To a solution of 3.0 g (0.026 mole) of 3-cis-chlorocyclopentanol and 2.1 g 
(0.026 mole) of pyridine dissolved in 50 ml of ethyl ether, a solution of 
2.52 g (0.015 mole) of epoxysuccinyl chloride dissolved in 5 ml of ethyl 
ether was added dropwise while being stirred and cooled at 0.degree. to 
-5.degree. C. Then, when a procedure as described in Example 7 was carried 
out, di-3'-cis-chlorocyclopentyl epoxysuccinate(EP-29) was obtained as an 
oil. Yield 3.5 g (85%), m.p.&gt;300.degree. C.(d.). IR.nu..sub.KBr 
(cm.sup.-1): 1745 (ester, carbonyl), 901 (epoxide). 
NMR(CDCl.sub.3).delta.: 0.90-2.50 (14H, m), 3.60 (2H, s), 4.86 (2H, b.s.). 
The following compounds were obtained from the corresponding materials by 
methods similar to that described in Example 9. 
di-3'-trans-methylcyclopentyl epoxysuccinate(EP-31), 
di-2'-trans-bromocyclopentylepoxysuccinate(EP-33). 
EXAMPLE 10 
When a procedure as described in Example 6(b) was carried out by using 
di-3'-cis-chlorocyclopentyl epoxysuccinate (1.0 g) instead of 
dicyclopentyl epoxysuccinate, 3'-cis-chlorocyclopentyl potassium 
epoxysuccinate(EP-30) was obtained as crystals. Yield 0.52 g (52%), m.p. 
164.degree.-170.degree. C.(d.). 
The following compounds were obtained from the corresponding materials by 
methods similar to that described in Example 10. 
3'-trans-methylcyclopentyl potassium epoxysuccinate(EP-32), 
2'-trans-bromocyclopentyl potassium epoxysuccinate(EP-34). 
EXAMPLE 11 
To a solution of 3.0 g (0.023 mole) of cyclooctanol and 1.8 g (0.023 mole) 
of pyridine dissolved in 50 ml of ethyl ether, a solution of 2.35 g (0.014 
mole) of epoxysuccinyl chloride dissolved in 5 ml of ethyl ether was added 
dropwise while being stirred and cooled at 0.degree. to -5.degree. C. 
After the mixture had been stirred for 30 to 60 min., the precipitated 
hydrogen chloride salt of pyridine was filtered out. The ethyl ether layer 
thus obtained was washed with water, dried over anhydrous sodium sulfate 
and distilled to dryness. The resulting residue was chromatographed on 
silica gel using n-hexane-acetone (10:1) mixture as solvent to give 
dicyclooctyl epoxysuccinate(EP-35) as an oil. Yield 3.4 g (88%). 
IR.nu..sub.KBr (cm.sup.-1): 1740 (ester, carbonyl), 898 (epoxide). 
NMR(CDCl.sub.3).delta.: 1.20-2.05 (28H, m), 3.55 (2H, s), 5.00 (2H, b.s.). 
EXAMPLE 12 
To a solution of 5.0 g (0.016 mole) of dicyclooctyl epoxysuccinate 
dissolved in 50 ml of dimethylformamide, 5.14 ml of aqueous 3 N potassium 
hydroxide solution was added dropwise while being stirred and cooled at 
0.degree. C. After the mixture had been stirred for 10 to 15 min., to 
this, 1000 ml of acetone was added. The formed crystals were filtered and 
recrystallized from water-acetone to give cyclooctyl potassium 
epoxysuccinate(EP-36) as colorless crystals. Yield 0.5 g (14%), 
m.p.&gt;300.degree. C.(d.). IR.nu..sub.KBr (cm.sup.-1): 1740 (ester, 
carbonyl), 1610 (COOK), 900 (epoxide). NMR (D.sub.2 O).delta.: 1.20-2.05 
(14H, m), 3.49,3.51 (2H, d.d., J=2 Hz), 4.79 (1H, m). 
EXAMPLE 13 
To a solution of 3.0 g (0.02 mole) of 2-adamantanol and 1.6 g (0.02 mole) 
of pyridine dissolved in 50 ml of ethyl ether, a solution of 2.0 g (0.012 
mole) of epoxysuccinyl chloride dissolved in 5 ml of ethyl ether was added 
dropwise while being stirred and cooled at 0.degree. to -5.degree. C. 
After the mixture had been stirred for 30 to 60 min., the precipitated 
hydrogen chloride salt of pyridine was filtered out. The ethyl ether layer 
thus obtained was washed with water, dried over anhydrous sodium sulfate 
and distilled to dryness. The resulting residue was chromatographed on 
silica gel using n-hexane-acetone (10:1) mixture as solvent to give 
di-2-adamantyl epoxysuccinate(EP-37) as colorless crystals. Yield 3.1 g 
(79%), m.p. 152.degree.-154.degree. C. (from n-hexane-acetone). 
EXAMPLE 14 
To a solution of 5.0 g (0.016 mole) of di-2-adamantyl epoxysuccinate 
dissolved in 50 ml of dimethylformamide, 5.14 ml of aqueous 3 N potassium 
hydroxide solution was added dropwise while being stirred and cooled at 
0.degree. C. When the mixture was treated by the method as described in 
Example 12, 2-adamantyl potassium epoxysuccinate(EP-38) was obtained as 
colorless crystals. Yield 0.5 g (14%), m.p.&gt;300.degree. C.(d.). 
IR.nu..sub.KBr (cm.sup.-1): 1740 (ester, carbonyl), 1618 (COOK), 900 
(epoxide). NMR(D.sub.2 O).delta.: 1.0-2.5 (14H, m), 3.49, 3.51 (2H, d.d., 
J=2 Hz), 5.00 (1H, m). 
EXAMPLE 15 
To a solution of 0.8 g (0.011 mole) of cyclopropanemethanol and 0.87 g 
(0.011 mole) of pyridine dissolved in 30 ml of ethyl ether, a solution of 
1.0 g (0.0006 mole) of epoxysuccinyl chloride dissolved in 3 ml of ethyl 
ether was added dropwise while being stirred and cooled at 0.degree. to 
-5.degree. C. After the mixture had been stirred for 30 to 50 min., the 
precipitated hydrogen chloride salt of pyridine was filtered out. The 
ethyl ether layer thus obtained was washed with water, dried over 
anhydrous sodium sulfate and distilled to dryness. The resulting residue 
was chromatographed on silica gel using n-hexane-acetone (10:1) mixture as 
solvent to give dicyclopropanemethyl epoxysuccinate(EP-39) as an oil. 
Yield 1.1 g (83%). Mass: m/e 240 (M.sup.+). IR.nu..sub.KBR (cm.sup.-1): 
1750 (ester, carbonyl), 901 (epoxide). NMR(CDCl.sub.3).delta.: 0.20-1.50 
(10H, m), 4.64 (2H, s), 4.99 (4H, d, J=7.2 Hz). 
EXAMPLE 16 
To a solution of 0.63 g (0.003 mole) of dicyclopropanemethyl epoxysuccinate 
dissolved in 10 ml of dimethylformamide, one ml of aqueous 3 N potassium 
hydroxide solution was added dropwise while being stirred and cooled at 
0.degree. C. After the mixture had been stirred for 10 to 15 min., to 
this, 500 ml of acetone was added. The formed crystals were filtered and 
recrystallized from acetone-water to give cyclopropanemethyl potassium 
epoxysuccinate(EP-40) as colorless crystals. Yield 0.15 g (26%), 
m.p.&gt;300.degree. C.(d). IR.nu..sub.KBr (cm.sup.-1): 1745 (ester, 
carbonyl), 1610 (COOK), 900 (epoxide). NMR(D.sub.2 O).delta.: 0.20-1.40 
(5H, m), 3.45, 3.58 (2H, d.d., J=2 Hz), 4.00 (2H, d., J=6 Hz). 
EXAMPLE 17 
To a solution of 3.0 g (0.026 mole) of cyclohexanemethanol and 2.1 g (0.026 
mole) of pyridine dissolved in 50 ml of ethyl ether, a solution of 2.52 g 
(0.015 mole) of epoxysuccinyl chloride dissolved in 5 ml of ethyl ether 
was added dropwise while being stirred and cooled at 0.degree. to 
-5.degree. C. After the mixture had been stirred for 30 to 60 min., the 
precipitated hydrogen chloride salt of pyridine was filtered. The ethyl 
ether layer thus obtained was washed with water, dried over anhydrous 
sodium sulfate and distilled to dryness. The resulting residue was 
chromatographed on silica gel using n-hexane-acetone (10:1) mixture as 
solvent to give dicyclohexanemethyl epoxysuccinate(EP-41) as an oil. Yield 
3.6 g (84%), b.p. 238.degree.-240.degree. C. (6 mmHg). 
The following compounds were obtained from the corresponding materials by 
methods similar to that described in Example 17. 
dicyclopentanemethyl epoxysuccinate(EP-43), 
di-1-cyclopentaneethyl epoxysuccinate(EP-45), 
di-1-adamantanemethyl epoxysuccinate(EP-47), 
di-2-(1-adamantane)ethyl epoxysuccinate(EP-49), 
dibicyclo [2,2,2] octyl epoxysuccinate(EP-51), 
dibornyl epoxysuccinate(EP-53), 
dinorbornyl epoxysuccinate(EP-55), 
dinorbor-5-en-2-yl epoxysuccinate(EP-57). 
EXAMPLE 18 
To a solution of 5.0 g (0.015 mole) of dicyclohexanemethyl epoxysuccinate 
dissolved in 50 ml of dimethylformamide, 5.14 ml of aqueous 3 N potassium 
hydroxide solution was added dropwise while being stirred and cooled at 
0.degree. C. After the mixture had been stirred for 10 to 15 min., to 
this, 1000 ml of acetone was added. The formed crystals were filtered and 
recrystallized from acetone-water to give cyclohexanemethyl potassium 
epoxysuccinate(EP-42) as colorless crystals. Yield 0.8 g (19%), 
mp.&gt;300.degree. C. (d.). IR.nu..sub.KBr (cm.sup.-1): 1740 (ester, 
carbonyl), 1620 (COOK), 900 (epoxide). NMR(D.sub.2 O).delta.: 1.0-2.3 
(10H, m), 3.94, 3.51 (2H, d.d., J=2 Hz), 4.85 (1H, m). 
The following compounds were obtained from the corresponding materials by 
the similar method as described in Example 18. 
cyclopentanemethyl potassium epoxysuccinate(EP-44), 
1-cyclopentaneethyl potassium epoxysuccinate(EP-46), 
1-adamantanemethyl potassium epoxysuccinate(EP-48), 2-(1-adamantane)ethyl 
potassium epoxysuccinate(EP-50), 
bicyclo [2,2,2] octyl potassium epoxysuccinate(EP-52), 
bornyl potassium epoxysuccinate(EP-54), 
norbornyl potassium epoxysuccinate(EP-56), 
norbor-5-en-2-yl potassium epoxysuccinate(EP-58). 
EXAMPLE 19 
To a solution of 3.0 g (0.026 mole) of 2-cyclopentaneethanol and 2.1 g 
(0.026 mole) of pyridine dissolved in 50 ml of ethyl ether, a solution of 
2.52 g (0.015 mole) of epoxysuccinyl chloride dissolved in 5 ml of ethyl 
ether was added dropwise while being stirred and cooled at 0.degree. to 
-5.degree. C. After the mixture had been stirred for 30 to 60 min., the 
precipitated hydrogen chloride salt of pyridine was filtered out. The 
ethyl ether layer thus obtained was washed with water, dried over 
anhydrous sodium sulfate and distilled to dryness. The resulting residue 
was chromatographed on silica gel using n-hexane-acetone (10:1) mixture as 
solvent to give di-2-cyclopentaneethyl epoxysuccinate(EP-59) as an oil. 
Yield 3.2 g (74%). 
IR.nu..sub.KBr (cm.sup.-1): 1750 (ester, carbonyl), 900 (epoxide). 
NMR(CDCl.sub.3).delta.: 0.80-2.10 (22H, m), 3.62 (2H, s), 4.18 (4H, t, 
J=6.7 Hz). 
The following compound was obtained from the corresponding material by the 
similar method as described in Example 19. 
di-2-cyclohexaneethyl epoxysuccinate(EP-61). 
EXAMPLE 20 
To a solution of 5.0 g (0.015 mole) of di-2-cyclopentaneethyl 
epoxysuccinate dissolved in 50 ml of dimethylformamide, 5.14 ml of aqueous 
3 N potassium hydroxide solution was added dropwise while being stirred 
and cooled at 0.degree. C. After the mixture had been stirred for 10 to 15 
min., to this, 1000 ml of acetone was added. The formed crystals were 
filtered and recrystallized from acetone-water to give 2-cyclopentaneethyl 
potassium epoxysuccinate(EP-60) as colorless crystals. Yield 1.1 g (27%), 
m.p.&gt;300.degree. C.(d.). IR.nu..sub.KBr (cm.sup.-1): 1740 (ester, 
carbonyl), 1610 (COOK), 900 (epoxide). NMR(D.sub.2 O).delta.: 0.90-2.10 
(11H, m), 3.44, 3.56 (2H, d.d., J=2 Hz), 4.18 (2H, t, J=6.7 Hz). 
The following compound was obtained from the corresponding material by a 
method similar to that described in Example 20. 
2-cyclohexaneethyl potassium epoxysuccinate(EP-62). 
EXAMPLE 21 
To a solution of 3.0 g (0.023 mole) of 3-cyclopentanepropanol and 1.82 g 
(0.023 mole) of pyridine dissolved in 50 ml of ethyl ether, a solution of 
2.0 g (0.012 mole) of epoxysuccinyl chloride dissolved in 5 ml of ethyl 
ether was added dropwise while being stirred and cooled at 0.degree. to 
-5.degree. C. After the mixture had been stirred for 30 to 60 min., the 
precipitated hydrogen chloride salt of pyridine was filtered. The ethyl 
ether layer thus obtained was washed with water, dried over anhydrous 
sodium sulfate and distilled to dryness. The resulting residue was 
chromatographed on silica gel using n-hexane-acetone (10:1) mixture as 
solvent to give di-3-cyclopentanepropyl epoxysuccinate(EP-63) as an oil. 
Yield 3.8 g (83%). IR.nu..sub.KBr (cm.sup.-1): 1750 (ester, carbonyl), 900 
(epoxide). NMR(CDCl.sub.3).delta.: 0.88-2.00 (26H, m), 3.12 (2H,s), 4.16 
(4H, t, J=6.7 Hz). 
The following compounds were obtained from the corresponding materials by 
methods similar to that described in Example 21. 
di-3-cyclohexanepropyl epoxysuccinate(EP-65), 
di-4-cyclohexanebutyl epoxysuccinate(EP-67). 
EXAMPLE 22 
To a solution of 5.0 g (0.014 mole) of di-3-cyclopentanepropyl 
epoxysuccinate dissolved in 50 ml of dimethylformamide, 5.14 ml of aqueous 
3 N potassium hydroxide solution was added dropwise while being stirred 
and cooled at 0.degree. C. After the mixture had been stirred for 10 to 15 
min., to this, 1000 ml of acetone was added. The formed crystals were 
filtered and recrystallized from acetone-water to give 
3-cyclopentanepropyl potassium epoxysuccinate(EP-64) as colorless 
crystals. Yield 0.5 g (13%), m.p.&gt;300.degree. C.(d.). IR.nu..sub.KBr 
(cm.sup.-1): 1730 (ester, carbonyl), 1610 (COOK), 900 (epoxide). 
NMR(D.sub.2 O).delta.: 0.80-2.10 (13H, m), 3.44, 3.56 (2H, d.d., J=2 Hz), 
4.15 (2H, t, J=6.7 Hz). 
The following compounds were obtained from the corresponding materials by a 
method similar to that described in Example 22. 
3-cyclohexanepropyl potassium epoxysuccinate(EP-66), 
4-cyclohexanebutyl potassium epoxysuccinate(EP-68). 
EXAMPLE 23 
To a solution of 3.0 g (0.027 mole) of 3-cyclohexane methanol and 2.1 g 
(0.027 mole) of pyridine dissolved in 50 ml of ethyl ether, a solution of 
2.52 g (0.015 mole) of epoxysuccinyl chloride dissolved in 5 ml of ethyl 
ether was added dropwise while being stirred and cooled at 0.degree. to 
-5.degree. C. After the mixture had been stirred for 30 to 60 min., the 
precipitated hydrogen chloride salt of pyridine was filtered out. The 
ethyl ether layer thus obtained was washed with water, dried over 
anhydrous sodium sulfate and distilled to dryness. The resulting residue 
was chromatographed on silica gel using n-hexane-acetone (10:1) mixture as 
solvent to give di-3-cyclohexenemethyl epoxysuccinate(EP-69) as an oil. 
Yield 3.5 g (81%). IR.nu..sub.KBr (cm.sup.-1): 1750 (ester, cabonyl), 900 
(epoxide). NMR(CDCl.sub.3).delta.: 1.10-2.50 (14H, m), 3.64 (2H, s), 4.07 
(4 H, d, J=7.2 Hz), 5.64 (4H, s). 
The following compounds were obtained from the corresponding materials by a 
method similar to that described in Example 23. 
di-2-cyclopentenemethyl epoxysuccinate(EP-71), 
di-4-cyclooctenemethyl epoxysuccinate(EP-73). 
EXAMPLE 24 
To a solution of 5.0 g (0.016 mole) of di-3-cyclohexenemethyl 
epoxysuccinate dissolved in 50 ml of dimethylformamide, 5.14 ml of aqueous 
3 N potassium hydroxide solution was added dropwise while being stirred 
and cooled at 0.degree. C. After the mixture had been stirred for 10 to 15 
min., to this, 1000 ml of acetone was added. The formed crystals were 
filtered and recrystallized from acetone-water to give 3-cyclohexenemethyl 
potassium epoxysuccinate(EP-70) as colorless crystals. Yield 0.7 g (17%), 
m.p.&gt;300.degree. C.(d.). IR.nu..sub.KBr (cm.sup.-1): 1740 (ester, 
carbonyl), 1610 (COOK), 900 (epoxide). NMR(D.sub.2 O).delta.: 1.00-2.30 
(7H, m), 3.45, 3.58 (2H, d.d., J=2 Hz), 4.07 (2H, d, J=6 Hz), 5.66 (2H, 
s). 
The following compounds were obtained from the corresponding materials by 
methods similar to that described in Example 24. 
2-cyclopentenemethyl potassium epoxysuccinate(EP72), 
4-cyclooctenemethyl potassium epoxysuccinate(EP-74). 
EXAMPLE 25 
To a solution of 3.0 g (0.029 mole) of tetrahydrofurfuryl alcohol 
(tetrahydro-2-furanmethanol) and 2.3 g (0.029 mole) of pyridine dissolved 
in 50 ml of ethyl ether, a solution of 2.6 g (0.016 mole) of epoxysuccinyl 
chloride dissolved in 5 ml of ethyl ether was added dropwise while being 
stirred and cooled at 0.degree. to -5.degree. C. After the mixture had 
been stirred for 30 to 60 min., the precipitated hydrogen chloride salt of 
pyridine was filtered out. The ethyl ether layer thus obtained was washed 
with water, dried over anhydrous sodium sulfate and distilled to dryness. 
The resulting residue was chromatographed on silica gel using 
n-hexane-acetone (10:1) mixture as solvent to give 
di-tetrahydro-2-furanmethyl epoxysuccinate(EP-75) as an oil. Yield 3.2 g 
(73%), b.p. 221.degree.-224.degree. C. (6 mmHg). 
The following compound was obtained from the corresponding material by a 
method similar to that described in Example 25. 
di-2-furanmethyl epoxysuccinate(EP-77). 
EXAMPLE 26 
To a solution of 5.0 g (0.016 mole) of di-tetrahydro-2-furanmethyl 
epoxysuccinate dissolved in 50 ml of dimethylformamide, 5.14 ml of aqueous 
3 N potassium hydroxide solution was added dropwise while being stirred 
and cooled at 0.degree. C. After the mixture had been stirred for 10 to 15 
min., to this, 1000 ml of acetone was added. The formed crystals were 
filtered and recrystallized from acetone-water to give 
tetrahydro-2-furanmethyl potassium epoxysuccinate(EP-76) as colorless 
crystals. Yield 0.6 g (16%), m.p.&gt;300.degree. C.(d.). IR.nu..sub.KBr 
(cm.sup.-1): 1740 (ester, carbonyl), 1610 (COOK), 901 (epoxide). 
NMR(D.sub.2 O).delta.: 1.00-2.3 (6H, m), 3.42, 3.51 (2H, d.d., J=2 Hz), 
4.20 (2H, t, J=6 Hz). 
The following compound was obtained from the corresponding material by a 
method similar to that described in Example 26. 
2-furanmethyl potassium epoxysuccinate(EP-78). 
EXAMPLE 27 
To a solution of 3.0 g (0.029 mole) of 2-thenyl alcohol 
(2-thiofuranmethanol) and 2.3 g (0.029 mole) of pyridine dissolved in 50 
ml of ethyl ether, a solution of 2.6 g (0.016 mole) of epoxysuccinyl 
chloride dissolved in 5 ml of ethyl ether was added dropwise while being 
stirred and cooled at 0.degree. to -5.degree. C. Then, when a procedure as 
described in Example 25 was carried out, di-2-thenyl epoxysuccinate(EP-79) 
was obtained as an oil. Yield 3.3 g (82%), m.p.&gt;300.degree. C.(d.). Mass: 
m/e 324 (M.sup.+). IR.nu..sub.KBr (cm.sup.-1): 1750 (ester, carbonyl), 900 
(epoxide). NMR(CDCl.sub.3).delta.: 3.75 (2H, s), 5.41 (4H, s), 6.95-7.85 
(6H, m). 
EXAMPLE 28 
When a procedure as described in Example 26 was carried out by using 
di-2-thenyl epoxysuccinate (1.9 g) instead of di-tetrahydro-2-furanmethyl 
epoxysuccinate, 2'-thenyl potassium epoxysuccinate(EP-80) was obtained as 
colorless crystals from water-acetone. Yield 0.90 g (47.6%), 
m.p.&gt;300.degree. C.(d.). IR.nu..sub.KBr (cm.sup.-1): 1745 (ester, 
carbonyl), 1620 (COOK), 902 (epoxide). NMR(D.sub.2 O).delta.: 3.44, 3.56 
(2H, d.d., J=2 Hz), 5.40 (2H, s), 6.96-7.35 (2H, m), 7.35-7.60 (1H, m). 
EXAMPLE 29 
To a solution of 3.0 g (0.025 mole) of 1-naphthyl-methanol and 2.0 g (0.025 
mole) of pyridine dissolved in 50 ml of ethyl ether, a solution of 2.35 g 
(0.014 mole) of epoxysuccinyl chloride dissolved in 5 ml of ethyl ether 
was dropped while being stirred and cooled at 0.degree. to -5.degree. C. 
Then, when a procedure as described in Example 23 was carried out, 
di-1'-naphthylmethyl epoxysuccinate(EP-81) was obtained as colorless 
needles. Yield 3.4 g (86%), m.p. 105.degree.-107.degree. C. (from 
n-hexane-acetone). 
The following compounds were obtained from the corresponding materials by 
the method as described in Example 29. 
di-2'-chloro-1'-naphthylmethyl epoxysuccinate(EP-83), 
di-5'-bromo-1'-naphthylmethyl epoxysuccinate(EP-85), 
di-4',5'-dimethyl-1'-naphthylmethyl epoxysuccinate(EP-87). 
EXAMPLE 30 
When the procedure as described in Example 18 was carried out by using 
di-1'-naphthylmethyl epoxysuccinate (1.9 g) instead of dicyclohexanemethyl 
epoxysuccinate, 1'-naphthylmethyl potassium epoxysuccinate(EP-82) was 
obtained as colorless crystals from water-acetone. Yield 0.92 g (45%), 
m.p. 185.degree.-188.degree. C. 
The following compounds were obtained from the corresponding materials by 
methods similar to that described in Example 30. 
2'-chloro-1'-naphthylmethyl potassium epoxysuccinate(EP-84), 
5'-bromo-1'-naphthylmethyl potassium epoxysuccinate(EP-86), 
4',5'-dimethyl-1'-naphthylmethyl potassium epoxysuccinate(EP-88). 
EXAMPLE 31 
To a solution of 3.0 g (0.025 mole) of p-methylbenzyl alcohol and 2.0 g 
(0.025 mole) of pyridine dissolved in 50 ml of ethyl ether, a solution of 
2.2 g (0.013 mole) of epoxysuccinyl chloride dissolved in 5 ml of ethyl 
ether was added dropwise while being stirred and cooled at 0.degree. to 
-5.degree. C. After the mixture had been stirred for 30 to 60 min., the 
precipitated hydrogen chloride salt of pyridine was filtered out. The 
ethyl ether layer thus obtained was washed with water, dried over 
anhydrous sodium sulfate and distilled to dryness. The resulting residue 
was chromatographed on silica gel using n-hexane-acetone (10:1) mixture as 
solvent to give di-p-methylbenzyl epoxysuccinate(EP-89) as colorless 
crystals. Yield 3.5 g (84%), m.p. 17.degree. C. (from n-hexane-acetone). 
The following compounds were obtained from the corresponding materials by a 
method as described in Example 31. 
di-o-methylbenzyl epoxysuccinate(EP-91), 
di-3',5'-dimethylbenzyl epoxysuccinate(EP-93), 
di-2',4',6'-trimethylbenzyl epoxysuccinate(EP-95), 
di-2'-bromo-3'-methylbenzyl epoxysuccinate(EP-97), 
di-3'-trifluoromethylbenzyl epoxysuccinate(EP-99). 
EXAMPLE 32 
To a solution of 1.9 g (0.0056 mole) of di-p-methylbenzylepoxysuccinate 
dissolved in 19 ml of dimethylformamide, 2.0 ml of aqueous 3 N potassium 
hydroxide solution was added dropwise while being stirred and cooled at 
0.degree. C. After the mixture had been stirred for 10 to 15 min., to 
this, 200 ml of acetone was added. The formed crystals were filtered and 
recrystallized from water-acetone to give p-methylbenzyl potassium 
epoxysuccinate (EP-90) as colorless crystals. Yield 0.80 g (46%), m.p. 
177.degree.-181.degree. C.(d.). 
The following compounds were obtained from the corresponding materials by 
the similar method as described in Example 32. 
o-methylbenzyl potassium epoxysuccinate(EP-92), 
3',5'-dimethylbenzyl potassium epoxysuccinate(EP-94), 
2',4',6'-trimethylbenzyl potassium epoxysuccinate(EP-96), 
2'-bromo-3'-methylbenzyl potassium epoxysuccinate(EP-98), 
3'-trifluoromethylbenzyl potassium epoxysuccinate(EP-100). 
EXAMPLE 33 
To a solution of 3.0 g (0.022 mole) of p-methoxybenzyl alcohol and 1.74 g 
(0.022 mole) of pyridine dissolved in 50 ml of ethyl ether, a solution of 
1.85 g (0.011 mole) of epoxysuccinyl chloride dissolved in 5 ml of ethyl 
ether was added dropwise while being stirred and cooled at 0.degree. to 
-5.degree. C. After the mixture had been stirred for 30 to 60 min., the 
precipitated hydrogen chloride salt of pyridine was filtered out. The 
ethyl ether layer thus obtained was washed with water, dried over 
anhydrous sodium sulfate and distilled to dryness. The resulting residue 
was chromatographed on silica gel using n-hexane-acetone (10:1) mixture as 
solvent to give di-p-methoxybenzyl epoxysuccinate(EP-101) as colorless 
needles. Yield 3.1 g (78%), m.p. 82.degree.-84.degree. C. (from 
n-hexane-acetone). 
The following compound was obtained from the corresponding material by a 
method as described in Example 33. 
di-methylene-3',4'-dioxybenzyl epoxysuccinate(EP-103). 
EXAMPLE 34 
To a solution of 1.9 g (0.0051 mole) of di-p-methoxybenzyl epoxysuccinate 
dissolved in 19 ml of dimethylformamide, 2.0 ml of aqueous 3 N potassium 
hydroxide solution was added dropwise while being stirred and cooled at 
0.degree. C. After the mixture had been stirred for 10 to 15 min., to 
this, 200 ml of acetone was added. The formed crystals were filtered and 
recrystallized from water-acetone to give p-methoxybenzyl potassium 
epoxysuccinate (EP-102) as colorless needles. Yield 0.95 g (47%), m.p. 
189.degree.-193.degree. C.(d.). 
The following compound was obtained from the corresponding material by a 
method as described in Example 34. 
methylene-3',4'-dioxybenzyl potassium epoxysuccinate(EP-104) 
EXAMPLE 35 
To a solution of 3.0 g (0.013 mole) of o-iodobenzyl alcohol and 1.0 g 
(0.013 mole) of pyridine dissolved in 50 ml of ethyl ether, a solution of 
1.2 g (0.007 mole) of epoxysuccinyl chloride dissolved in 5 ml of ethyl 
ether was added dropwise while being stirred and cooled at 0.degree. to 
-5.degree. C. After the mixture had been stirred for 30 to 60 min., the 
precipitated hydrogen chloride salt of pyridine was filtered out. The 
ethyl ether layer thus obtained was washed with water, dried over 
anhydrous sodium sulfate and distilled to dryness. The resulting residue 
was chromatographed on silica gel using n-hexane-acetone (10:1) mixture as 
solvent to give di-o-iodobenzyl epoxysuccinate(EP-105) as colorless 
needles. Yield 3.0 g (83%), m.p. 111.degree.-112.degree. C. 
The following compounds were obtained from the corresponding materials by a 
method as described in Example 35. 
di-o-chlorobenzyl epoxysuccinate(EP-107), 
di-m-chlorobenzyl epoxysuccinate(EP-109), 
di-p-iodobenzyl epoxysuccinate(EP-111), 
di-p-bromobenzyl epoxysuccinate(EP-113), 
di-p-chlorobenzyl epoxysuccinate(EP-115), 
di-2',4'-dichlorobenzyl epoxysuccinate(EP-117), 
di-2'-bromo-4'-iodobenzyl epoxysuccinate(EP-119). 
EXAMPLE 36 
To a solution of 4.5 g (0.008 mole) of di-o-iodobenzyl epoxysuccinate 
dissolved in 35 ml of dimethylformamide, 2.7 ml of aqueous 3 N potassium 
hydroxide solution was added dropwise while being stirred and cooled at 
0.degree. C. After the mixture had been stirred for 10 to 15 min., to 
this, 500 ml of acetone was added. The formed crystals were filtered and 
recrystallized from water-acetone to give o-iodobenzyl potassium 
epoxysuccinate(EP-106) as a colorless amorphous solid. Yield 0.9 g (29%). 
IR.nu..sub.KBr (cm.sup.-1): 1718 (ester, carbonyl), 1610 (COOK), 900 
(epoxide). NMR(D.sub.2 O).delta.: 3.48, 3.62 (2H,d.d., J=2 Hz), 5.14 (2H, 
s), 6.87-7.52 (4H, m). 
The following compounds were obtained from the corresponding materials by a 
method as described in Example 36. 
o-chlorobenzyl potassium epoxysuccinate(EP-108), 
m-chlorobenzyl potassium epoxysuccinate(EP-110), 
p-iodobenzyl potassium epoxysuccinate(EP-112), 
p-bromobenzyl potassium epoxysuccinate(EP-114), 
p-chlorobenzyl potassium epoxysuccinate(EP-116), 
2',4'-dichlorobenzyl potassium epoxysuccinate(EP-118), 
2'-bromo-4'-iodobenzyl potassium epoxysuccinate(EP-120). 
EXAMPLE 37 
To a solution of 3.0 g (0.024 mole) of m-fluorobenzyl alcohol and 1.9 g 
(0.024 mole) of pyridine dissolved in 50 ml of ehtyl ether, a solution of 
2.0 g (0.012 mole) of epoxysuccinyl chloride dissolved in 5 ml of ethyl 
ether was added dropwise while being stirring and cooling at 0.degree. to 
-5.degree. C. After the mixture had been stirred for 30 to 60 min., the 
precipitated hydrogen chloride salt of pyridine was filtered out. The 
ethyl ether layer thus obtained was washed with water, dried over 
anhydrous sodium sulfate and distilled to dryness. The resulting residue 
was chromatographed on silica gel using n-hexane-acetone (10:1) mixture as 
solvent to give di-m-fluorobenzyl epoxysuccinate(EP-121) as an oil. Yield 
3.1 g (75%). IR.nu..sub.KBr (cm.sup.-1): 1720 (ester, carbonyl), 899 
(epoxide). NMR(CDCl.sub.3).delta.: 3.52 (2H, s), 5.10 (4H, s), 6.87-7.52 
(8H, m). 
The following compounds were obtained from the corresponding materials by a 
method as described in Example 37. 
di-o-fluorobenzyl epoxysuccinate(EP-123), 
di-3'-chloro-4'-bromobenzyl epoxysuccinate(EP-125), 
di-2',5'-dichlorobenzyl epoxysuccinate(EP-127). 
EXAMPLE 38 
To a solution of 5.0 g (0.0114 mole) of di-m-fluorobenzyl epoxysuccinate 
dissolved in 35 ml of dimethylformamide, 4.8 ml of aqueous 3 N potassium 
hydroxide solution was added dropwise while being stirred and cooled at 
0.degree. C. After the mixture had been stirred for 10 to 15 min., to 
this, 500 ml of acetone was added. The formed crystals were filtered and 
recrystallized from water-acetone to give m-fluorobenzyl potassium 
epoxysuccinate(EP-122) as a colorless amorphous solid. Yield 1.1 g (25%). 
IR.nu..sub.KBr (cm.sup.-1): 1740 (ester, carbonyl), 1610 (COOK), 900 
(epoxide). NMR(D.sub.2 O).delta.:3.48, 3.62 (2H, d.d., J=2 Hz), 5.14 (2H, 
s), 6.85-7.52 (4H, m). 
The following compounds were obtained from the corresponding materials by a 
method as described in Example 38. 
o-fluorobenzyl potassium epoxysuccinate(EP-124), 
3'-chloro-4'-bromobenzyl potassium epoxysuccinate(EP-126), 
2',5'-dichlorobenzyl potassium epoxysuccinate(EP-128). 
EXAMPLE 39 
To a solution of 3.0 g (0.025 mole) of 2-phenylethanol and 2.0 g (0.025 
mole) of pyridine dissolved in 50 ml of ethyl ether, a solution of 2.35 g 
(0.014 mole) of epoxysuccinyl chloride dissolved in 5 ml of ethyl ether 
was added dropwise while being stirred and cooled at 0.degree. to 
-5.degree. C. After the mixture had been stirred for 30 to 60 min., the 
precipitated hydrogen chloride salt of pyridine was filtered. The ethyl 
ether layer thus obtained was washed with water, dried over anhydrous 
sodium sulfate and distilled to dryness. The resulting residue was 
chromatographed on silica gel using n-hexane-acetone (10:1) mixture as 
solvent to give di-2'-phenylethyl epoxysuccinate(EP-129) as an oil. Yield 
3.2 g (79%). IR.nu..sub.KBr (cm.sup.-1): 1750 (ester, carbonyl), 901 
(epoxide). NMR(CDCl.sub.3).delta.: 2.93 (4H, t, J=6.7 Hz), 3.50 (2H, s), 
4.36 (4H, t, J=6.7 Hz), 7.17 (10H, s). 
The following compound was obtained from the corresponding materials by a 
method as described in Example 39. 
di-3'-phenylpropyl epoxysuccinate(EP-131). 
EXAMPLE 40 
To a solution of 3.3 g (0.01 mole) of di-2'-phenylethyl epoxysuccinate 
dissolved in 30 ml of dimethylformamide, 3.3 ml of aqueous 3 N potassium 
hydroxide solution was added dropwise while being stirred and cooled at 
0.degree. C. After the mixture had been stirred for 10 to 15 min., to 
this, 1000 ml of acetone was added. The formed crystals were filtered and 
recrystallized from acetone-water to give 2'-phenylethyl potassium 
epoxysuccinate(EP-130) as colorless crystals. Yield 0.85 g (38%), m.p. 
&gt;300.degree. C.(d.). IR.nu..sub.KBr (cm.sup.-1): 1745 (ester, carbonyl), 
1610 (COOK), 900 (epoxide). NMR(D.sub.2 O).delta.: 0.70-2.00 (13H, m), 
3.41, 3.53 (2H, d.d., J=2 Hz), 4.20 (2H, t, J=6 Hz). 
The following compound was obtained from the corresponding material by the 
method as described in Example 40. 
3'-phenylpropyl potassium epoxysuccinate(EP-132). 
EXAMPLE 41 
To a solution of 3.0 g (0.025 mole) of 3-phenyl-2-propen-1-ol (cinnamyl 
alcohol) and 2.0 g (0.025 mole) of pyridine dissolved in 50 ml of ethyl 
ether, a solution of 2.35 g (0.014 mole) of epoxysuccinyl chloride 
dissolved in 5 ml of ethyl ether was added dropwise while being stirred 
and cooled at 0.degree. to -5.degree. C. Then, when the procedure as 
described in Example 39 was carried out, di-3'-phenyl-2'-propenyl 
epoxysuccinate(EP-133) was obtained as colorless needles. Yield 3.1 g 
(78%), m.p. 165.degree. C. (from n-hexane-acetone). 
EXAMPLE 42 
When the procedure as described in Example 40 was carried out by using 
di-3'-phenyl-2'-propenyl epoxysuccinate (1.9 g) instead of 
di-2'-phenylethyl epoxysuccinate, 3'-phenyl-2'-propenyl potassium 
epoxysuccinate(EP-134) was obtained as colorless crystals from 
water-acetone. Yield 0.98 g (48%), m.p. 153.degree.-155.degree. C. 
EXAMPLE 43 
To a solution of 2.4 g of dimethyl epoxysuccinate in 45 ml of methanol, a 
solution of 0.84 g of potassium hydroxide in 8.4 ml of methanol was added 
with ice-cooling. The mixture was stirred for two hours and concentrated 
in vacuo. The residue was dissolved in 30 ml of water and acidified with 
concentrated sulfuric acid. The resulting solution was extracted 5 times 
with 30 ml of ethyl acetate. The ethyl acetate layers were combined and 
concentrated to dryness. Recrystallization of the residue from 
chloroform-hexane gave 1.31 g of methyl hydrogen epoxysuccinate(EP-135) as 
white plates. Yield 48%, m.p. 85.degree.-86.degree. C. IR.nu..sub.KBr 
(cm.sup.-1): 1760 (ester), 1715 (COOH), 900 (epoxide). 
NMR(CDCl.sub.3).delta.: 3.77 (2H, s), 3.88 (3H, s), 9.95 (1H, s). 
The following compound was obtained from the corresponding material by the 
method as described in Example 43. 
phenyl hydrogen epoxysuccinate(EP-136). 
EXAMPLE 44 
To a solution of 9 g of diethyl epoxysuccinate in 30 ml of ethanol, 2.7 g 
of potassium hydroxide in 72 ml ethanol was added with ice-cooling. The 
mixture was stirred for two hours, and the deposited solid was collected 
by filtration and washed with a small amount of ethanol. Recrystallization 
from aqueous ethanol gave 6.8 g of ethyl potassium epoxysuccinate(EP-137) 
as white prisms. Yield 72.5%. IR.nu..sub.KBr (cm.sup.-1): 1735 (ester), 
1620 (COOK), 905 (epoxide). NMR(D.sub.2 O).delta.: 1.3 (3H, t, J=7 Hz), 
3.59 (2H, d.d., J=2 Hz), 4.29 (2H, q, J=7 Hz). 
The following compounds were obtained from the corresponding materials by 
the method as described in Example 44. 
n-propyl potassium epoxysuccinate(EP-138), 
i-propyl potassium epoxysuccinate(EP-139), 
allyl potassium epoxysuccinate(EP-140), 
propargyl potassium epoxysuccinate(EP-141), 
n-butyl potassium epoxysuccinate(EP-142), 
benzyl potassium epoxysuccinate(EP-143). 
EXAMPLE 45 
To a solution of 8.16 g of di-n-amyl epoxysuccinate in 3 ml of n-amyl 
alcohol, a solution of 1.68 g of potassium hydroxide in 12 ml of amyl 
alcohol was added with ice-cooling. The mixture was stirred for 40 minutes 
and added to petroleum ether. After cooling at -10.degree. C., the 
crystals thus obtained were collected and washed with petroleum ether to 
give 2.6 g of n-amyl potassium epoxysuccinate(EP-144). Yield 36%. 
IR.nu..sub.Nujol (cm.sup.-1): 1740 (ester), 1620 (COOK), 900 (epoxide). 
NMR(D.sub.2 O).delta.: 0.85 (3H, t, J=6 Hz), 1.00-2.00 (6H, m), 3.53 (2H, 
d.d., J=2 Hz), 4.19 (2H, t, J=6 Hz). d.d., J=2 Hz), 4.19 (2H, t, J=6 Hz). 
The following compound was obtained from the corresponding material by the 
similar method as described in Example 45. 
n-dodecyl potassium epoxysuccinate(EP-145). 
EXAMPLE 46 
To a solution of 1.98 g of ethyl potassium epoxysuccinate (i.e. ethyl 
potassium oxirane 2,3-dicarboxylate) in 50 ml of ethyl ether, a solution 
of 1.4 g of oxalyl chloride in 30 ml of ethyl ether was added dropwise 
while being stirred and cooled by ice for 30 min. After the mixture had 
been stirred additionally at room temperature for 2 hours, the formed 
precipitate was filtered. The filtrate was concentrated by evaporation 
under reduced pressure to give epoxysuccinic acid monoethyl ester chloride 
as an oil. Then, the acid chloride was dissolved in 30 ml of ethyl ether 
and the solution thus obtained was added dropwise to a solution of 1.6 g 
of L-leucine ethyl ester and 1.1 g of triethylamine dissolved in 50 ml of 
ethyl ether while being stirred and cooled by ice for 30 min. After the 
mixture had been stirred additionally at room temperature for three hours, 
the formed precipitate was filtered. The filtrate was evaporated under 
reduced pressure to give an oil. The oil thus obtained was further 
purified by silica gel column chromatography using chloroform-acetone 
(100:5) mixture as solvent to give 
N-(3-ethoxycarbonyloxirane-2-carbonyl)-L-leucine ethyl ester(EP-146) as a 
colorless oil. Yield 1.9 g (63%). Mass: m/e 301 (M.sup.+). IR.nu..sub.film 
(cm.sup.-1): 3370 (amine), 1748 (ester), 1680, 1545 (amide), 895 
(epoxide). NMR(CDCl.sub.3).delta.: 0.95 (6H, d, J=5 Hz), 1.26 (3H, t, J=7 
Hz), 1.29 (3H, t, J=7 Hz), 1.64 (3H, m), 3.42 (0.5 H, d, J=2 Hz), 3.51 
(0.5 H, d, J=2 Hz), 3.67 (1H, d, J=2 Hz), 4.20 (4H, q, J=2 Hz), 4.6 (1H, 
m), 6.35 (1H, b.). 
EXAMPLE 47 
When 0.65 g of epoxysuccinic acid monoallylester chloride which was 
prepared from 1.0 g of allyl potassium epoxysuccinate (i.e. allyl 
potassium oxirane 2,3-dicarboxylate) by treatment with oxalyl chloride in 
a manner as described in Example 46 was reacted with L-tyrosine benzyl 
ester in dichloromethane by the method as described in Example 46, 
N-(3-allyloxycarbonyloxirane-2-carbonyl)-L-tyrosine benzyl ester(EP-147) 
was obtained as a colorless oil. Yield 1.0 g (68%). Mass: m/e 425 
(M.sup.+). IR.nu..sub.film (cm.sup.-1): 3480 (amine, hydroxy), 1755 
(ester), 1685, 1525 (amide), 1625 (C.dbd.C), 895 (epoxide). 
NMR(CDCl.sub.3).delta.: 2.98 (2H, d, J=6 Hz), 3.19 (0.5H, d, J=2 Hz), 3.43 
(0.5H, d, J=2 Hz), 3.58 (0.5H, d, J=2 Hz), 3.61 (0.5H, d, J=2 Hz), 4.5-6.2 
(6H, m), 5.08 (2H, d, J=3 Hz), 6.25-7.0 (4H, m), 7.25 (5H, s). 
EXAMPLE 48 
When epoxysuccinic acid mono m-methylbenzyl ester chloride which was 
prepared from m-methylbenzyl potassium epoxysuccinate (i.e. m-methylbenzyl 
potassium oxirane 2,3-dicarboxylate) in a manner as described in Example 
46 was reacted with L-tyrosine benzyl ester in dichloromethane by the same 
method as described in Example 47, 
N-(3-m-methylbenzyloxycarbonyloxirane-2-carbonyl)-L-tyrosine benzyl 
ester(EP-148) was obtained as a colorless oil. Yield 61%. Mass: m/e 489 
(M.sup.+). IR.nu..sub.film (cm.sup.-1): 3480 (amine, hydroxy), 1750 
(ester, 1685, 1540 (amide), 897 (epoxide). NMR(CDCl.sub.3).delta.: 2.30 
(3H, s), 3.02 (2H, d, J=6 Hz), 3.21 (0.5H, d, J=2 Hz), 3.47 (0.5H, d, J=2 
Hz), 3.60 (0.5H, d, J=2 Hz), 3.64 (0.5H, d, J=2 Hz), 4.75 (1H, m), 5.12 
(4H, s), 6.35 (1H, b), 6.25-7.20 (8H, m), 7.30 (5H, s). 
The following compounds were obtained from the corresponding materials by 
similar methods as described in Example 48. 
N-(3-piperonyloxycarbonyloxirane-2-carbonyl)-L-methionene methyl 
ester(EP-149), 
N-(3-ethoxycarbonyloxirane-2-carbonyl)-L-phenylalanine ethyl ester(EP-150), 
N-(3-ethoxycarbonyloxirane-2-carbonyl)-L-tryptophan ethyl ester(EP-151), 
N-(3-ethoxycarbonyloxirane-2-carbonyl)-L-proline benzyl ester(EP-152), 
N-(3-n-propyloxycarbonyloxirane-2-carbonyl)-glycine benzyl ester(EP-153), 
N-(3-ethoxycarbonyloxirane-2-carbonyl)-glycine benzyl ester(EP-154), 
N-(3-ethoxycarbonyloxirane-2-carbonyl)-L-methionine methyl ester(EP-155), 
N-(3-ethoxycarbonyloxirane-2-carbonyl)-L-glutamic acid dibenzyl 
ester(EP-156), 
N-(3-ethoxycarbonyloxirane-2-carbonyl)-.beta.-alanine benzyl ester(EP-157), 
N-(3-ethoxycarbonyloxirane-2-carbonyl)-L-valine benzyl ester(EP-158), 
N-(3-benzyloxycarbonyloxirane-2-carbonyl)-L-phenylalanine ethyl 
ester(EP-159), 
N-(3-o-chlorobenzyloxycarbonyloxirane-2-carbonyl)-L-phenylalanine ethyl 
ester(EP-160), 
N-(3-anisyloxycarbonyloxirane-2-carbonyl)-L-proline benzyl ester(EP-161), 
N-(3-p-bromobenzyloxycarbonyloxirane-2-carbonyl)-L-valine benzyl 
ester(EP-162), 
N.sup..alpha. -(3-ethoxycarbonyloxirane-2-carbonyl)-N.sup..epsilon. 
-carbobenzoxy-L-lysine benzyl ester(EP-163), 
N.sup..alpha. -(3-allyloxycarbonyloxirane-2-carbonyl)-N.sup..epsilon. 
-carbobenzoxy-L-lysine benzyl ester(EP-164), 
N.sup..alpha. -(3-propargyloxycarbonyloxirane-2-carbonyl)-N.sup..epsilon. 
-carbobenzoxy-L-lysine benzyl ester(EP-165), 
N-(3-methoxycarbonyloxirane-2-carbonyl)-L-leucine ethyl ester(EP-166), 
N-(3-ethoxycarbonyloxirane-2-carbonyl)-L-leucine amide (EP-167), 
N-(3-ethoxycarbonyloxirane-2-carbonyl)-L-glutamine benzyl ester(EP-168), 
N.sup..alpha. -(3-ethoxycarbonyloxirane-2-carbonyl)-N.sup..epsilon. 
-p-methoxybenzyloxycarbonyl-L-lysine benzyl ester(EP-169), 
N.sup..alpha. -(3-ethoxycarbonyloxirane-2-carbonyl)-N.sup..epsilon. 
-t-butyloxycarbonyl-L-lysine benzyl ester(EP-170), 
N.sup..alpha. -(3-benzyloxycarbonyloxirane-2-carbonyl-N.sup..epsilon. 
-formyl-L-lysine benzyl ester(EP-171), 
N.sup..alpha. -(3-ethoxycarbonyloxirane-2-carbonyl)-N.sup..delta. 
-acetyl-L-ornithine benzyl ester(EP-172), 
N.sup..alpha. -(3-ethoxycarbonyloxirane-2-carbonyl)-N.sup..delta. 
-benzoyl-L-ornithine benzyl ester(EP-173). 
EXAMPLE 49 
To a solution of 0.5 g of N-(3-ethoxycarbonyloxirane-2-carbonyl)-L-leucine 
ethyl ester(EP-146) dissolved in 2 ml of ethanol and 1 ml of water, a 
solution of 0.3 g of potassium hydroxide dissolved in 1 ml of water was 
added. After the mixture had been stirred at room temperature for 2 hours, 
40 ml of ethanol was added to the mixture. The formed precipitate was 
filtered and recrystallized from ethanol-water to give 
N-(3-carboxyoxirane-2-carbonyl)-L-leucine dipotassium salt(EP-174) as 
colorless needles. Yield 0.32 g (60%), m.p. 210.degree. C. 
The following compounds were obtained by a method as described in Example 
49. 
N-(3-carboxyoxirane-2-carbonyl)-L-phenylalanine dipotassium salt(EP-175), 
N-(3-carboxyoxirane-2-carbonyl)-N-carbobenzoxy-L-lysine dipotassium 
salt(EP-176). 
EXAMPLE 50 
After saponification of 0.15 g of 
N-(ethoxycarbonyloxirane-2-carbonyl)-L-tryptophan ethyl ester with 
potassium hydroxide in an analogous experiment of Example 49, the reaction 
mixture was acidified with hydrochloric acid and extracted with ethyl 
ether. Evapolation of the solvent gave 
N-(3-carboxyoxirane-2-carbonyl)-L-tryptophan(EP-177) as colorless powders. 
Yield 0.1 g (87%), m.p. 113.degree. C. 
EXAMPLE 51 
To a solution of 5.1 g of N.sup.G -nitro-L-arginine benzyl ester 
ditosylate, 1.7 g of benzyl hydrogen epoxysuccinate (i.e. benzyl hydrogen 
oxirane 2,3-trans dicarboxylate), 1.6 g of methyl morpholine and 1.3 g of 
N-hydroxysuccinimide dissolved in 30 ml of dimethylformamide, a solution 
of 3.0 g of dicyclohexylcarbodiimide dissolved in 20 ml of 
dimethylformamide was added dropwise with stirring at -10.degree. C. The 
mixture was stirred for one hour at -10.degree. C. and for another one 
hour at room temperature and was allowed to stand overnight. After 
filtration of the precipitate thus formed, the filtrate was diluted with 
200 ml of ethyl acetate and washed with saturated sodium bicarbonate 
solution and saturated sodium chloride, in turn. The organic layer was 
dried over magnesium sulfate and evaporated to dryness. Silica gel column 
chromatography using chloroformmethanol (25:1) as solvent and 
recrystallization from acetone-n-hexane provided 
N-(3-benzyloxycarbonyloxirane-2-carbonyl)-N.sup.G -nitro-L-arginine benzyl 
ester(EP-178) as colorless needles. Yield 2.4 g (61%), m.p. 
141.degree.-142.degree. C. 
The following compounds were obtained by a method as described in Example 
51. 
N.sup..alpha. -(phenoxycarbonyloxirane-2-carbonyl)-N.sup..epsilon. 
-carbobenzoxy-L-lysine benzyl ester(EP-179), 
N.sup..alpha. -(3-iso-propyloxycarbonyloxirane-2-carbonyl)-N.sup..epsilon. 
-carbobenzoxy-L-lysine benzyl ester(EP-180), 
N.sup..alpha. 
-(3-p-methylbenzyloxycarbonyloxirane-2-carbonyl)-N.sup..epsilon. 
-carbobenzoxy-L-lysine benzyl ester(EP-181), 
N.sup..alpha. -(3-benzyloxycarbonyloxirane-2-carbonyl)-N.sup..delta. 
-carbobenzoxy-L-ornithine benzyl ester(EP-182), 
N.sup..alpha. -(3-n-buthoxycarbonyloxirane-2-carbonyl)-N.sup..delta. 
-carbobenzoxy-L-ornithine benzyl ester(EP-183), 
N.sup..alpha. -(3-benzyloxycarbonyloxirane-2-carbonyl)-N.sup.G 
-nitro-L-arginine methyl ester(EP-184), 
N.sup..alpha. -(3-ethoxycarbonyloxirane-2-carbonyl)-L-histidine methyl 
ester(EP-185), 
N.sup..alpha. -(3-ethoxycarbonyloxirane-2-carbonyl)-L-serine ethyl 
ester(EP-186), 
N.sup..alpha. -(3-phenethyloxycarbonyloxirane-2-carbonyl)-N.sup..epsilon. 
-carbobenzoxy-L-lysine benzyl ester(EP-187), 
N.sup..alpha. 
-[3-(3'-phenylpropyloxy)-carbonyloxirane-2-carbonyl]-N.sup..epsilon. 
-carbobenzoxy-L-lysine benzyl ester(EP-188), 
N-(3-p-chlorobenzyloxycarbonyloxirane-2-carbonyl)-.gamma.-aminobutylic acid 
ethyl ester(EP-189), 
N-(3-methoxycarbonyloxirane-2-carbonyl)-L-threonine ethyl ester(EP-190), 
N-(3-benzyloxycarbonyloxirane-2-carbonyl)-S-benzyl-L-cysteine benzyl 
ester(EP-191), 
N-(3-ethoxycarbonyloxirane-2-carbonyl)-L-alanine-t-butyl ester(EP-192), 
N-(3-ethoxycarbonyloxirane-2-carbonyl)-L-aspartic acid dibenzyl 
ester(EP-193), 
N-(3-ethoxycarbonyloxirane-2-carbonyl)-L-asparagine benzyl ester(EP-194). 
EXAMPLE 52 
To a solution of 0.512 g of N.sup..alpha. 
-(3-ethoxycarbonyloxirane-2-carbonyl)-N.sup..epsilon. 
-carbobenzoxy-L-lysine ethyl ester in 10 ml of ethanol, a solution of 
0.056 g of potassium hydroxide in 5 ml of ethanol was added dropwise under 
ice cooling. The precipitate thus formed was filtered and reprecipitated 
from water-ethanol to give N.sup..alpha. 
-(3-carboxyoxirane-2-carbonyl)-N.sup..epsilon. -carbobenzoxy-L-lysine 
ethyl ester potassium salt(EP-195) as a colorless powder. Yield 0.32 g 
(75%), m.p. 148.degree.-149.degree. C. 
The following compounds were obtained from the corresponding materials by a 
method as described in Example 51. 
N.sup..alpha. -(3-carboxyoxiane-2-carbonyl)-N.sup..delta. 
-carbobenzoxy-L-ornithine benzyl ester potassium salt(EP-196), 
N.sup..alpha. -(3-carboxyoxirane-2-carbonyl)-N.sup..epsilon. 
-carbobenzoxy-L-lysine benzyl ester potassium salt(EP-197), 
N.sup..alpha. -(3-carboxyoxirane-2-carbonyl)-N.sup..delta. 
-carbobenzoxy-L-ornithine methyl ester potassium salt(EP-198), 
N.sup..alpha. -(3-carboxyoxirane-2-carbonyl)-N.sup..delta. 
-carbobenzoxy-L-ornithine n-butyl ester potassium salt(EP-199), 
EXAMPLE 53 
A mixture of 0.4 g of N-(3-benzyloxycarbonyloxirane-2-carbonyl)-N.sup.G 
-nitro-L-arginine methyl ester(EP-184) dissolved in 25 ml of the 
methanol-acetic acid-water (8/2/1=v/v/v) mixture was stirred in the 
presence of 0.1 g of 5% palladium carbon under stream of H.sub.2 at room 
temperature for 4 hours. After removal of catalyst by filtration, the 
filtrate was evaporated under reduced pressure to give an oil. This was 
dissolved in water and extracted with ethyl acetate. The aqueous layer was 
evaporated under reduced pressure to give a solid. Further purification of 
this by Sephadex LH-20 column chromatography (Farmacia Co.) using 5% 
aqueous methanol solution as solvent afforded 
N-(3-carboxyoxirane-2-carbonyl)-L-arginine methyl ester(EP-200) as 
colorless glassy crystals. Yield 0.21 g (76%), m.p. 99.degree.-102.degree. 
C. 
The following compounds were obtained from the corresponding materials by a 
method as described in Example 53. 
N-(3-ethoxycarbonyloxirane-2-carbonyl)-L-lysine(EP-201), 
N-(3-carboxyoxirane-2-carbonyl)-L-arginine(EP-202). 
EXAMPLE 54 
By substituting one g of L-leucine ethyl ester hydrochloride and 1.2 g of 
3'-cyclopentyl-propyl hydrogen epoxysuccinate for N.sup.G 
-nitro-L-arginine benzyl ester ditosylate and benzyl hydrogen 
epoxysuccinate in Example 51, 
N-[3-(3'-cyclopentylpropyloxy)carbonyloxirane-2-carbonyl]-L-leucine ethyl 
ester(EP-203) was obtained as an oil. Yield 1.2 g (62%). Mass: m/e 383 
(M.sup.+). IR.nu..sub.film (cm.sup.-1): 3370 (amine), 1750 (ester), 1680, 
1545 (amide), 895 (epoxide). NMR(CDCl.sub.3).delta.: 0.95 (6H, d, J=5 Hz), 
1.30 (3H, t, J=7 Hz), 0.8-2.1 (16H, m), 3.42 (0.5H, d, J=2 Hz), 3.53 
(0.5H, d, J=2 Hz), 3.67 (1H, d, J=2 Hz), 4.05 (2H, t, J=7 Hz), 4.13 (2H, 
q, J=7 Hz), 4.2-4.8 (1H, m), 6.0-6.7 (1H, b.). 
The following compounds were obtained from the corresponding material by a 
method as described in Example 54. 
N.sup..alpha. -(3-cyclopropyloxycarbonyloxirane-2-carbonyl)-N.sup..epsilon. 
-carbobenzoxy-L-lysine benzyl ester(EP-204), 
N-(3-cyclopentyloxycarbonyloxirane-2-carbonyl)-L-valine benzyl 
ester(EP-205), 
N-[3-(1'-cyclopentylethoxy)-carbonyloxirane-2-carbonyl]-L-lysine benzyl 
ester(EP-206), 
N-[3-(2'-cyclohexylethoxy)-carbonyloxirane-2-carbonyl]-glycine benzyl 
ester(EP-207), 
N-[3-(4'-cyclohexylbutoxy)-carbonyloxirane-2-carbonyl]-.beta.-alanine 
benzyl ester(EP-208), 
N-(3-cyclooctyloxycarbonyloxirane-2-carbonyl)-L-glutamic acid dibenzyl 
ester(EP-209), 
N-[3-(2'-adanatyloxy)-carbonyloxirane-2-carbonyl]-L-phenyl alanine ethyl 
ester(EP-210), 
N-[3-(3'-cyclohexen-1-yl)-methoxycarbonyloxirane-2-carbonyl]-L-tyrosine 
benzyl ester(EP-211). 
EXAMPLE 55 
By substituting 1.14 g of 2-cis-methylcyclohexyl hydrogen epoxysuccinate 
and 1.2 g of L-phenylalanine ethyl ester hydrochloride for benzyl hydrogen 
epoxysuccinate and N.sup.G -nitro-L-arginine benzyl ester ditosylate in 
Example 51, 
N-[3-(2'-cis-methylcyclohexyloxy)carbonyloxirane-2-carbonyl]-L-phenylalani 
ne ethyl ester(EP-212) was obtained as an oil. Yield 1.1 g (54.6%). Mass: 
m/e 403 (M.sup.+). IR.nu..sub.film (cm.sup.-1): 3400 (amine), 1753 
(ester), 1680, 1540 (amide), 897 (epoxide). NMR(CDCl.sub.3).delta.: 0.88 
(3H, d, J=7 Hz), 1.20 (1.5H, t, J=7 Hz), 1.22 (1.5H, t, J=7 Hz), 1.45 (8H, 
b, s.), 3.06 (2H, d, J=6 Hz), 3.15 (0.5H, d, J=2 Hz), 3.47 (0.5H, d, J=2 
Hz), 3.58 (0.5H, d, J=2 Hz), 3.62 (0.5H, d, J=2 Hz), 4.0 (1H, q, J=7 Hz), 
4.15 (1H, q, J=7 Hz), 4.5-5.0 (1H, m), 5.02 (1H, b.s.), 5.12 (1H, s), 
6.2-6.5 (1H, b.s.), 6.8-7.4 (5H, m). 
The following compounds were obtained from the corresponding material by a 
method as described in Example 55. 
N-[3-(2'-cis-chlorocyclopentyloxy)-carbonyloxirane-2-carbonyl]-glycine 
benzyl ester(EP-213), 
N-[3-(2'-trans-bromocyclopentyloxy)-carbonyloxirane-2-carbonyl]-L-leucine 
benzyl ester(EP-214), 
N-[3-(4'-trans-methylcyclohexyloxy)-carbonyloxirane-2-carbonyl]-L-alanine 
methyl ester(EP-215). 
EXAMPLE 56 
By substituting 1.14 g of thenyl hydrogen epoxysuccinate and 2.7 g of 
L-glutamic acid dibenzyl ester tosylate for benzyl hydrogen epoxysuccinate 
and N.sup.G -nitro-L-arginine benzyl ester ditosylate in Example 51, 
N-(3-thenyloxycarbonyloxirane-2-carbonyl)-L-glutamic acid dibenzyl 
ester(EP-216) was obtained as an oil. Yield 1.5 g (55.9%). Mass: m/e 537 
(M.sup.+). IR.nu..sub.film (cm.sup.-1): 3400 (amine), 1755 (ester), 1690, 
1540 (amide), 895 (epoxide). NMR(CDCl.sub.3).delta.: 2.0-2.6 (4H, m), 3.45 
(1H, d, J=2 Hz), 3.62 (1H, d, J=2 Hz), 4.4-4.8 (1H, m), 5.05 (2H, s), 5.10 
(2H, d, J=2 Hz), 5.42 (2H, s), 6.5-6.9 (1H, b.), 6.9-7.9 (3H, m), 7.29 
(10H, s). 
The following compounds were obtained from the corresponding materials by a 
method as described in Example 56. 
N-[3-furfuryloxycarbonyloxirane-2-carbonyl]-L-leucine n-butyl 
ester(EP-217), 
N-[3-tetrahydrofurfuryloxycarbonyloxirane-2-carbonyl]-L-phenylalanine 
t-butyl ester(EP-218), 
N-[3-(1'-naphthylmethoxycarbonyloxirane-2-carbonyl]-L-valine ethyl 
ester(EP-219), 
N-[3-(5'-bromo-2-naphthylmethoxy)-carbonyloxirane-2-carbonyl]-glycine ethyl 
ester(EP-220).