Cyclopropene derivatives with thiol protease inhibiting activity

Abstract: The cyclopropene derivatives of the present invention are useful as the intermediates for producing cyclopropenone derivatives exhibiting strong inhibition activity of thiol protease such as calpain, papain, cathepsin B, cathepsin H, cathepsin L and the like.

Description: FIELD OF THE INVENTION The present invention relates to novel cyclopropene derivatives, and more specifically, the present invention relates to novel cyclopropene derivatives useful as intermediates for the production of cyclopropenone derivatives having strong inhibitory activity against thiol protease such as calpain, papain, cathepsin B, cathepsin H, cathepsin L and the like, or the salts thereof. BACKGROUND OF THE INVENTION As the biological action of thiol protease such as calpain, papain, cathepsin B, cathepsin H, cathepsin L. etc. has been elucidated, it has been found that the abnormal increase thereof is the cause of various diseases, so that the inhibitors of thiol protease have been used as their therapeutical agents of those diseases. For example, reports have been issued that calpain inhibitors have effects on animal models with muscular dystrophy, cataract, myocardial infarction, delayed death of neurocytes after brain infarction, and the like, while cathepsin inhibitors have effects on cancer metastasis, amyotrophy, osteoporosis and the like. However, because known inhibitors of thiol proteases, such as peptidyl aldehydes, epoxy succinate derivatives, etc., are poor in oral administration, tissue distribution, and cell membrane permeability, expectation has been toward the development of novel thiol protease inhibitors which can overcome these problems. EP-A-0 520 427 which forms state of the art in the sense of Article 54(3) EPC discloses cyclopropenone derivatives excluded from the scope of the present invention, which have a potent inhibitory activity against thiol protease. SUMMARY OF THE INVENTION Thus, the present inventors have made investigations of the intermediate for the production of a thiol protease inhibitor showing excellent oral administration, tissue distribution, and cell membrane permeability. Then, the inventors have achieved the present invention. The present invention resides in cyclopropene derivatives represented by the general formula (I): [In the above general formula (I), R 1 represents hydrogen atom or a protective group of amino group; R 2 represents hydrogen atom, a protective group of amino group or C 1 -C 5 alkyl group; or when R 1 and R 2 are taken together, they represent phthaloyl group (i.e. they form a phthalimide with the nitrogen atom); R 4 an R 6 independently represent hydrogen atom or C 1 -C 5 alkyl group; R 3 and R 5 independently represent hydrogen atom or C 1 -C 15 alkyl group optionally substituted with C 3 -C 10 cycloalkyl group or C 6 -C 10 aryl group; or when R 5 and R 6 are taken together, they represent C 2 -C 6 alkylene group; R 7 and R 8 represent -OR 10 and -OR 11 , respectively (wherein R 10 and R 11 independently represent C 1 -C 5 alkyl group optionally substituted with phenyl group: or when R 10 and R 11 are taken together, they represent C 2 -C 6 alkylene group optionally substituted with one or more C 1 -C 5 alkyl groups); or when R 7 and R 8 are taken together, they represent =O; R 9 represents hydrogen atom, C 1 -C 15 alkyl group, C 3 -C 10 cycloalkyl group, C 2 -C 15 alkenyl group, C 6 -C 10 aryl group optionally substituted with a substituent, heterocyclic group optionally substituted with a substituent, or -CR 12 R 13 OH (wherein R 12 and R 13 independently represent hydrogen atom, C 1 -C 15 alkyl group or C 6 -C 10 aryl group; or when R 12 and R 13 are taken together to form C 3 -C 10 cycloalkyl group); and n represents 0 or 1, provided that when n represents 1, R 7 , when taken together with R 8 does not represent =O, and further provided that when R 1 represents a tert-butoxycarbonyl group and n represents 0, R 7 and R 8 when taken together do not represent =O or a 2,2-dimethyl-propylenedioxy group] and the salts thereof. DETAILED DESCRIPTION OF THE INVENTION The present invention will now be explained in details. The compound of the present invention is cyclopropene derivatives represented by the general formula (I): [In the above general formula (I), R 1 represents hydrogen atom or a protective group of amino group (urethane-type protective group such as methoxycarbonyl group, tert-butoxycarbonyl group, benzyloxycarbonyl group. 4-methoxybenzyloxycarbonyl group, 4-chlorobenzyloxycarbonyl group, 3,5-dimethoxybenzyloxycarbonyl group, 3,4,5-trimethoxybenzyloxycarbonyl group, 9-fluorenylmethoxycarbonyl group, etc.; acyl-type protective group such as formyl group, trifluoroacetyl group, p-toluene sulfonyl group, 2,4,6-trimethylbenzene sulfonyl group, benzoyl group, chloroacetyl group, etc.; alkyl-type protective group such as benzyl group, diphenylmethyl group, trityl group, etc.); R 2 represents hydrogen atom, a protective group of amino group (which is as defined for R 1 ) or C 1 -C 5 alkyl group (methyl group, propyl group, pentyl group, etc.); or when R 1 and R 2 are taken together, they represent phthaloyl group; R 4 and R 6 independently represent hydrogen atom or C 1 -C 5 alkyl group (methyl group, propyl group, pentyl group, etc.); R 3 and R 5 independently represent hydrogen atom or C 1 -C 15 alkyl group (methyl group, hexyl group, decyl group, pentadecyl group, etc.) optionally substituted with C 3 -C 10 cycloalkyl group (cyclopropyl group, cyclopentyl group, cyclodecyl group, etc.) or C 6 -C 10 aryl group (phenyl group, naphtyl group, etc.); or when R 5 and R 6 are taken together, they represent C 2 -C 6 alkylene group (ethylene group, tetramethylene group, hexamethylene group, etc.); R 7 and R 8 represent -OR 10 and -OR 11 , respectively (wherein R 10 and R 11 independently represent C 1 -C 5 alkyl group (methyl group, propyl group, pentyl group, etc.) optionally substituted with phenyl group; or when R 10 and R 11 are taken together, they represent C 2 -C 6 alkylene group (ethylene group, tetramethylene group, hexamethylene group, etc.) optionally substituted with one or more C 1 -C 5 alkyl groups (methyl group, propyl group, pentyl group, etc.); or when R 7 and R 8 are taken together, they represent =O; R 9 represents hydrogen atom; C 1 -C 15 alkyl group (methyl group, hexyl group, decyl group, pentadecyl group, etc.); C 3 -C 10 cycloalkyl group (cyclopropyl group, cyclopentyl group, cyclodecyl group, etc.); C 2 -C 15 alkenyl group (vinyl group, hexenyl group, undecenyl group, pentadecenyl group, etc.); C 6 -C 10 aryl group (phenyl group, naphtyl group, etc.) optionally substituted with one or more substituents selected from the group consisting of halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom, etc.), C 1 -C 5 alkyl group (methyl group, propyl group, pentyl group, etc.), hydroxyl group and C 1 -C 5 alkoxy group (methoxy group, propoxy group, pentyloxy group, etc.); a heterocyclic group having one to four hetero atoms selected from the group consisting of oxygen atom, sulfur atom and nitrogen atom with the total number of the atoms constituting the ring being in the range of from 5 to 10 (furane ring, thiophene ring, pyridine ring, pyridine oxide ring, pyrimidine ring, pyridazine ring, benzofurane ring, benzothiophene ring, quinoline ring, naphthyridine ring, etc.), and optionally substituted with one or more substituents selected from the group consisting of C 3 -C 12 trialkylsilyl groups (trimethylsilyl groups, triethylsilyl groups, tert-butyldimethylsilyl groups, etc.), halogen atoms (fluorine atoms, chlorine atoms, bromine atoms, iodine atoms, etc.), C 1 -C 5 alkyl groups (methyl groups, propyl groups, pentyl groups, etc.), hydroxyl groups and C 1 -C 5 alkoxy groups (methoxy groups, propoxy groups, pentyloxy groups, etc.); or -CR 12 R 13 OH (wherein R 12 and R 13 independently represent hydrogen atom, C 1 -C 15 alkyl group (methyl group, hexyl group, decyl group, pentadecyl group, etc.) or C 6 -C 10 aryl group (phenyl group, naphthyl group, etc.); or when R 12 and R 13 are taken to form C 3 -C 10 cycloalkyl group (cyclopropyl group, cyclopentyl group, cyclodecyl group, etc.): and n represents 0 or 1, provided that when n represents 1, R 7 , when taken together with R 8 does not represent =O and further provided that when R 1 represents a tert-butoxycarbonyl group and n represents O, R 7 and R 8 when taken together do not represent =O or a 2,2-dimethyl-propylenedioxy group] and the salts thereof. Particularly preferable is a compound of the formula (I) in which R 1 represents hydrogen atom, tert-butoxycarbonyl group, benzyloxycarbonyl group, methoxycarbonyl group, 9-fluorenylmethoxycarbonyl group, p-toluene sulfonyl group. or trityl group; R 2 , R 4 and R 6 independently represent hydrogen atom or C 1 -C 3 alkyl group; or when R 1 and R 2 are taken together, they represent phthaloyl group; R 3 and R 5 independently represent hydrogen atom or C 1 -C 5 alkyl group optionally substituted with C 3 -C 8 cycloalkyl group, phenyl group or naphtyl group; or R 5 , when taken together with R 6 represents C 3 -C 6 cycloalkyl group; R 7 and R 8 represent-OR 10 and -OR 11 , respectively (wherein R 10 and R 11 independently represent C 1 -C 3 alkyl group optionally substituted with phenyl group; or R 10 , when taken together with R 11 represents C 2 -C 4 alkylene group optionally substituted with one or more C 1 -C 3 alkyl groups; or R 7 , when taken together with R 8 represents =O; R 9 represents hydrogen atom; C 1 -C 6 alkyl group; C 3 -C 8 cycloalkyl group; C 2 -C 8 alkenyl group; phenyl group or naphtyl group each optionally substituted with one or more substituents selected from the group consisting of halogen atom, C 1 -C 5 alkyl group and C 1 -C 5 alkoxy group; heterocyclic group having one to four hetero atoms selected from the group consisting of oxygen atom, sulfur atom and nitrogen atom with the total number of the atoms constituting the ring being in the range of from 5 to 10, and optionally substituted with one or more substituents selected from the group consisting of halogen atom, C 1 -C 5 alkyl group, C 1 -C 5 alkoxy group and C 3 -C 12 trialkylsilyl group; or -CR 12 R 13 OH (wherein R 12 and R 13 independently represent hydrogen atoms. C 1 -C 3 alkyl groups or phenyl groups); and n represents 0 or 1, provided that when n represents 1, R 7 , when taken together with R 8 does not represent =0, and further provided that when R 1 represents a tert-butoxycarbonyl group and n represents 0, R 7 and R 8 when taken together do not represent =O or a 2,2-dimethyl-propylenedioxy group. Most preferable is a compound of the formula (I) in which R 1 represents hydrogen atom, tert-butoxycarbonyl group, benzyloxycarbonyl group or methoxycarbonyl group; R 2 , R 4 and R 6 independently represent hydrogen atoms or C 1 -C 3 alkyl groups; R 3 and R 5 independently represent hydrogen atoms or C 1 -C 5 alkyl groups optionally substituted with a phenyl group; R 7 and R 8 represent -OR 10 and -OR 11 , respectively (wherein R 10 , when taken together with R 1 represents C 2 -C 4 alkylene group optionally substituted with one or more substituents selected from C 1 -C 3 alkyl groups; or R 7 , when taken together with R 8 represents =0; R 9 represents a hydrogen atom; a C 1 -C 6 alkyl group; a C 2 -C 8 alkenyl group; a phenyl group optionally substituted with one or more substituents selected from the group consisting of halogen atoms and C 1 -C 5 alkyl groups; a furyl group or a thienyl group each optionally substituted with one or more C 3 -C 12 trialkylsilyl groups; or -CR 12 R 13 OH (wherein R 12 and R 13 independently represent hydrogen atoms, C 1 -C 3 alkyl group or phenyl group); and n represents 0 or 1, provided that when n represents 1, R 7 , when taken together with R 8 does not represent =O, and further provided that when R 1 represents a tert-butoxycarbonyl group and n represents 0, R 7 and R 8 when taken together do not represent =O or a 2,2-dimethyl-propylenedioxy group. The asymmetric carbons present in the cyclopropene derivatives represented by the above general formula (I) independently form (R), (S) or (RS) configuration. Specific examples of the compounds in accordance with the present invention are shown in tables. Table 1 shows the compounds wherein R 7 and R 8 represent -OR 10 and -OR 11 , respectively, and n is zero; Table 2 shows the compounds wherein R 7 , taken together with R 8 represents =0, and n is zero; Table 3 shows the compounds wherein n is one and R 7 and R 8 represent -OR 10 and -OR 11 , respectively. In the Tables, 1, 2 and 3, Boc represents a tert-butoxycarbonyl group; Z represents a benzyloxycarbonyl group; pMZ represents a 4-methoxybenzyloxycarbonyl group; Moc represents a methoxycarbonyl group; Fmoc represents a 9-fluorenylmethoxycarbonyl group; Tfa represents a trifluoroacetyl group; Tos represents a p-toluene sulfonyl group; Mts represents a 2,4,6-trimethylbenzene sulfonyl group; Trt represents a trityl group; and Pht represents a phthalyl group. The process for the production of the compounds of the present invention will now be explained. The cyclopropene derivatives of the present invention may be produced, for example, by the following process: Process 1: A process for producing a compound represented by the above general formula (I) wherein R 7 and R 8 represent -OR 10 and -OR 11 , respectively: (In the above general formula, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 9 , R 10 , R 11 and n are those as defined above.) Using the known process described in the reference (Tetrahedron Letters, Vol.32, pp.1339, 1991), cyclopropenone ketal derivative represented by the above general formula (II) is readily synthesized. The derivative is dissolved in an ethereal solvent such as tetrahydrofuran, diethylether, etc., followed by addition of a strong base such as n-butyl lithium, methyl lithium, lithium diisopropylamide in the presence of an additive such as tetramethylethylenediamine, hexamethylphosphoric triamide, 1,3-dimethyl-2-imidazolidone, etc. to prepare a lithiated compound thereof. Then, an aldehyde derivative represented by the above general formula (III) is added to the resulting lithiated compound to prepare the cyclopropene derivative represented by the above general formula (1-a). In the reaction, anhydrous cerium chloride suspension in a solvent such as tetrahydrofuran, diethylether, hexane and the like may further be added to the lithiated compound of the resulting compound (II) to transform the compound into the cerium salt thereof, with which the aldehyde derivative represented by the general formula (III) may be reacted. Process 2: A process for producing a compound represented by the above general formula (I) wherein R 7 , taken together with R 8 represents =O, and n is zero: (In the above general formula, R 1 , R 2 , R 5 , R 6 , R 9 , R 10 , and R 11 are those as defined above.) The cyclopropene derivative represented by the above general formula (I-a)', produced by the process of Process 1, is dissolved in acetone, diethyl ether, tetrahydrofuran, etc., followed by treatment with an ion exchange resin such as Amberlist 15 (registered trade mark) or followed by addition of a mineral acid such as dilute sulfuric acid to effect selective deprotection of ketal, whereby the cyclopropene derivative represented by the above general formula (I-b) is produced. By the process described in Japanese Patent Application No. Hei 4-146024, the cyclopropene derivative represented by the above general formula (I) can be lead to cyclopropenone derivatives exhibiting a strong inhibitory activity against thiol protease such as calpain, papain, cathepsin B, cathepsin H, cathepsin L and the like. The present invention will now be described in examples hereinbelow. Example 1 Preparation of 2-((2S)-2-tert-butoxycarbonylamino-1-hydroxy-3-methylbutyl)-3-phenylcyclopropenone 2,2-dimethyl-1,3-propanediyl acetal (Compound No. 65 in Table 1) To a solution of 3.51 g of 2-phenylcyclopropenone 2,2-dimethyl-1,3-propanediyl acetal in 30 mℓ of tetrahydrofuran was added 3.8 g of N, N, N', N'-tetramethylethylenediamine. To the reaction solution chilled at -78 °C was added a 1.55 moℓ/ℓ solution of n-butyl lithium in 10.5 mℓ of hexane, and the mixture was stirred for 20 minnutes. Then, 30 mℓ of tetrahydrofuran suspension of anhydrous cerium chloride prepared by drying 8.0 g of cerium chloride heptahydrate at 140 °C/l mmHg for 2 hours was added to the mixture, which was stirred for 20 minutes. A solution of 1.82 g of N-tert-butoxycarbonyl-L-valinal in 20 mℓ of tetrahydrofuran was added, and the resultant mixture was stirred at -78 °C for 2 hours. A solution of 1 mℓ of water in 5 mℓ of tetrahydrofuran was added to the reaction mixture, which was allowed to warm at room temperature and filtered through celite®. The celite® was washed well with ethyl acetate, and the filtrate was dried over sodium sulfate, filtered, concentrated and chromatographed on a column of silica gel, eluting with hexane containing 20 % ethyl acetate as a developing solvent to give 2.71 g of the titled product. Yield: 72 % IR (KBr, cm -1 ): 3430, 2960, 1855, 1800, 1710, 1690 NMR (CD 3 OD, δ): 0.95-1.60 (m, 12H), 1.38 (s, 3H), 1.42 (s, 6H), 1.95-2.15 (m, 1H), 3.60-3.75 (m, 1H), 3.75-3.95 (m, 4H), 5.0-5.10 (m, 1H), 6.03 (d, J=10Hz, 0.33H), 6.23 (d, J=10Hz, 0.67H), 7.40-7.65 (m, 3H), 7.70-7.90 (m, 2H) In the same manner as in Example 1, the following compounds were produced. Example 2 Preparation of 2-(2-tert-butoxycarbonylamino-1-hydroxyethyl)cyclopropenone 2,2-dimethyl-1,3-propanediyl acetal (Compound No. 1 in Table 1) NMR (CDCℓ 3 , δ): 0.97 (s, 3H), 1.09 (s, 3H), 1.44 (s, 9H), 3.35-3.60 (m, 2H), 3.63 (s, 4H), 4.80-4.88 (m, 1H), 5.07-5.26 (m, 1H), 5.26-5.52 (m, 1H), 7.63 (s, 1H) Example 3 Preparation of 2-((2S)-2-tert-butoxycarbonylamino-1-hydroxy-3-methylbutyl)cyclopropenone 2,2-dimethyl-1,3-propanediyl acetal (Compound No. 3 in Table 1) IR (neat, cm -1 ): 3380, 1722, 1708, 1690 NMR (CDCℓ 3 , δ): 0.87-1.10 (m, 12H), 1.43 (s, 7.2H), 1.45 (s, 1.8H), 2.05-2.20 (m, 1H), 3.35-3.70 (m, 5H), 4.80-5.03 (m, 2H), 7.57 (s, 0.8H), 7.71 (s, 0.2H) Example 4 Preparation of 2-((2S)-2-tert-butoxycarbonylamino-1-hydroxy-4-methylpentyl)cyclopropenone 2,2-dimethyl-1,3-propanediyl acetal (Compound No. 6 in Table 1) IR (neat, cm -1 ): 3445, 3360, 1705 NMR (CDCℓ 3 , δ): 0.80-0.95 (m, 9H), 1.15 (s, 3H), 1.44 (s, 9H), 1.55-1.78 (m, 3H), 3.63 (s, 2H), 3.65 (s, 2H), 3.72-3.95 (m, 1H), 4.70-4.84.(m, 2H), 5.02-5.15 (m, 1H), 7.68 (s, 0.9H), 7.71 (s, 0.1H) Example 5 Preparation of 2-((2S)-2-tert-butoxycarbonylamino-1-hydroxyhexyl)cyclopropenone 2,2-dimethyl-1,3-propanediyl acetal (Compound No. 14 in Table 1) IR (neat, cm -1 ): 3460, 3370, 1700 NMR (CDCℓ 3 , δ): 0.85-1.0 (m, 3H), 0.92 (s, 3H), 1.14 (s, 3H), 1.25-1.55 (m, 6H), 1.44 (s, 9H), 3.05-3.15 (m, 0.7H), 3.25-3.35 (m, 0.3H), 3.61 (s, 2H), 3.63 (s, 2H), 3.65-3.85 (m, 0.7H), 3.85-4.05 (m, 0.3H), 4.70-4.85 (m, 1H), 4.85-4.95 (m, 0.3H), 5.0-5.15 (m, 0.7H), 7.65 (s, 0.7H), 7.72 (s, 0.3H) Example 6 Preparation of 2-((2S)-2-benzyloxycarbonylamino-1-hydroxyhexyl)cyclopropenone 2,2-dimethyl-1,3-propanediyl acetal (Compound No. 16 in Table 1) IR (neat, cm -1 ): 3360, 1723 NMR (CDCℓ 3 , δ): 0.75-0.98 (m, 6H), 1.08 (s, 1.5H), 1.12 (s, 1.5H), 1.18-1.60 (m, 6H), 3.04 (s, 0.5H), 3.32 (d, J=7.8Hz, 0.5H), 3.55-3.70 (m, 4H), 3.80 (m, 0.5H), 4.01 (m, 0.5H), 4.76 (d, J=7.8Hz, 0.5H), 4.83 (m, 0.5H), 5.11 (s, 2H), 5.13 (m, 0.5H), 5.63 (d, J=8.1Hz, 0.5H), 7.65 (s, 0.5H), 7.73 (s, 0.5H) Example 7 Preparation of 2-((2S)-2-tert-butoxycarbonylamino-1-hydroxyhexyl)-3-methylcyclopropenone 2,2-dimethyl-1,3-propanediyl acetal (Compound No. 32 in Table 1) NMR (CDCℓ 3 , δ): 0.84-0.96 (m, 3H), 0.95 (s, 3H), 1.08 (s, 3H), 1.28-1.55 (m, 6H), 1.43 (s, 9H), 2.17 (s, 3H), 3.53-3.80 (m, 5H), 4.63-4.74 (m, 1H), 4.88-5.07 (m, 1H) Example 8 Preparation of 2-((2S)-2-tert-butoxycarbonylamino-1-hydroxy-4-methylpentyl)-3-ethylcyclopropenone 2,2-dimethyl-1,3-propanediyl acetal (Compound No. 34 in Table 1) IR (neat, cm -1 ): 3360, 1853, 1696, 1623 NMR (CDCℓ 3 , δ): 0.88-1.01 (m, 12H), 1.32 (t, J=7.7Hz, 3H), 1.37-1.55 (m, 2H), 1.41 (s, 9H), 1.60-1.78 (m, 1H), 2.69 (q, J=7.7Hz, 2H), 3.55-3.70 (m, 4H), 3.79-4.02 (m, 1H), 4.67-4.78 (m, 1H), 4.80-5.03 (m, 1H), 5.16 -5.22 (m, 1H) Example 9 Preparation of 2-((2S)-2-tert-butoxycarbonylamino-1-hydroxyhexyl)-3-isopentylcyclopropenone 2,2-dimethyl-1,3-propanediyl acetal (Compound No. 41 in Table 1) IR (neat, cm -1 ): 3360, 1816, 1715, 1698 NMR (CDCℓ 3 , δ): 0.78-0.98 (m, 12H), 1.11 (s, 3H), 1.18-1.77 (m, 9H), 1.43 (s, 9H), 2.53 (d, J=7.6Hz, 2H), 3.56-3.80 (m, 5H), 4.65-4.80 (m, 1H), 4.98-5.12 (m, 1H) Example 10 Preparation of 2-((1S, 2S)-2-tert-butoxycarbonylamino-1-hydroxyhexyl)-3-((Z)-l-hexenyl)cyclopropenone 2,2-dimethyl-1,3-propanediyl acetal (Compound No. 53 in Table 1) IR (neat, cm -1 ): 3440, 1785, 1703 NMR (CDCℓ 3 , δ): 0.80-0.97 (m, 9H), 1.19 (s, 3H), 1.21-1.80 (m, 10H), 1.43 (s, 9H), 2.35-2.50 (m, 2H), 2.82 (s, 1H), 3.57-3.82 (m, 5H), 4.66-4.85 (m, 2H), 5.82-6.06 (m, 2H) Example 11 Preparation of 2-[(2S)-2-(N-tert-butoxycarbonyl)methylamino-l-hydroxy-3-methylbutyl]-3-phenylcyclopropenone 2,2-dimethyl-1,3-propanediyl acetal (Compound No. 74 in Table 1) IR (KBr, cm -1 ): 3430, 1798, 1688, 1672 NMR (CD 3 OD, δ): 0.80-1.35 (m, 12H), 1.45 (s, 9H), 2.30 (m, 1H), 2.69 (s, 1.5H), 2.72 (s, 1.5H), 3.65-3.90 (m, 4H), 4.09 (m, 1H), 5.02 (m, 1H), 7.30-7.52 (m, 3H), 7.70-7.82 (m, 2H) Example 12 Preparation of 2-((2S)-2-tert-butoxycarbonylamino-1-hydroxyhexyl)-3-phenylcyclopropenone 2,2-dimethyl-1,3-propanediyl acetal (Compound No. 76 in Table 1) IR (KBr, cm -1 ): 3310, 1800, 1720, 1792 NMR (CDCℓ 3 , δ): 0.80-0.98 (m, 3H), 0.99 (s, 3H), 1.21 (s, 3H), 1.15-1.90 (m, 6H), 1.39 (s, 2.7H), 1.43 (s, 6.3H), 3.58 (m, 0.7H), 3.68-4.95 (m, 4.6H), 4.95-4.10 (m, 0.7H), 4.88-5.07 (m, 1.3H), 5.24 (d, J=7.4Hz, 0.7H), 7.28-7.45 (m, 3H), 7.69 (d, J=6.5Hz, 2H) Example 13 Preparation of 2-(2-tert-butoxycarbonylamino-1-hydroxy-2-methylpropyl)-3-phenylcyclopropenone 2,2-dimethyl-1,3-propanediyl acetal (Compound No. 82 in Table 1) IR (KBr, cm -1 ): 3290, 1800, 1673 NMR (CDCℓ 3 , δ): 0.94 (s, 3H), 1.25 (s, 3H), 1.27 (s, 9H), 1.41 (s, 3H), 1.64 (s, 3H), 3.70-3.90 (m, 4H), 4.77 (d, J=8.6Hz, 1H), 4.93 (s, 1H), 5.57 (s, 1H), 7.28-7.46 (m, 3H), 7.75 (dd, J=8.2Hz, 1.4Hz, 2H) Example 14 Preparation of 2-((2S)-2-tert-butoxycarbonylamino-1-hydroxy-3-methylbutyl)-3-(4-fluorophenyl) cyclopropenone 2,2-dimethyl-1,3-propanediyl acetal (Compound No. 90 in Table 1) IR (KBr, cm -1 ): 3340, 1802, 1710, 1695, 1602 NMR (CD 3 OD, δ): 0.90-1.25 (m, 12H), 1.38 (s, 6.3H), 1.42 (s, 2.7H), 2.08 (m, 1H), 3.63 (m, 1H), 3.70-3.93 (m, 4H), 5.08 (d, J=4.5Hz, 0.3H), 5.02 (d, J=4.5Hz, 0.7H), 6.05 (d, J=10Hz, 0.3H), 6.19 (d, J=10Hz, 0.7H), 7.18-7.30 (m, 2H), 7.70-7.88 (m, 2H) Example 15 Preparation of 2-((2S)-2-tert-butoxycarbonylamino-1-hydroxyhexyl)-3-(2-tolyl)cyclopropenone 2,2-dimethyl-1,3propanediyl acetal (Compound No. 105 in Table 1) NMR (CDCℓ 3 , δ): 0.83-1.03 (m, 3H), 0.96 (s, 3H), 1.25 (s, 3H), 1.25-1.51 (m, 4H), 1.40 (s, 1.8H), 1.43 (s, 7.2H), 1.60-1.95 (m, 2H), 2.45 (s, 0.6H), 2.52 (s, 2.4H), 3.65-3.90 (m, 1H), 3.73 (s, 4H), 4.80-5.20 (m, 2H), 7.05-7.30 (m, 3H), 7.55-7.65 (m, 1H) Example 16 Preparation of 2-((2S)-2-tert-butoxycarbonylamino-1-hydroxyhexyl)-3-(5-trimethylsilyl-2-furyl)cyclopropenone 2,2dimethyl-1,3-propanediyl acetal (Compound No. 130 in Table 1) NMR (CDCℓ 3 , δ): 0.28 (s, 9H), 0.85-0.95 (m, 6H), 1.22 (s, 3H), 1.21-1.85 (m, 15H), 3.65-4.05 (m, 5H), 4.805.20 (m, 3H), 6.70 (d, J=3.9Hz, 1H), 6.78 (d, J=3.9Hz, 1H). Example 17 Preparation of 2-((2S)-2-tert-butoxycarbonylamino-1-hydroxyhexyl)-3-(5-trimethylsilyl-2-thienyl)cyclopropenone 2,2dimethyl-1,3-propanediyl acetal (Compound No. 139 in Table 1) NMR (CDCℓ 3 , δ): 0.34 (s, 3H), 0.84-0.97 (m, 6H), 1.24 (s, 3H), 1.27-1.50 (m, 13H), 1.55-1.92 (m, 2H), 3.64-4.04 (m, 5H), 4.83-5.30 (m, 2H), 7.21 (d, J=3.4Hz, 1H), 7.38 (d, J=3.4Hz, 1H) Example 18 Preparation of 2-((2S)-2-tert-butoxycarbonylamino-1-hydroxy-3-methylbutyl)-3-(1-hydroxy-1-methylethyl)cyclopropenone 2,2-dimethyl-1,3-propanediyl acetal (Compound No. 147 in Table 1) NMR (CDCℓ 3 , δ): 0.92-1.07 (m,12H), 1.41-1.53 (m, 15H), 1.80-2.05 (m, 1H), 3.56-3.78 (m, 5H), 4.84-4.90 (m, 1H), 5.10 (d, J=11Hz, 0.3H), 5.26 (d, J=11Hz, 0.7H), 6.0 (s, 2H) Example 19 Preparation of 2-((2S)-2-tert-butoxycarbonylamino-1-hydroxy-3-methylbutyl)-3-[(hydroxy)(phenyl)methyl]cyclopropenone 2,2-dimethyl-1,3-propanediyl acetal (Compound No. 156 in Table 1) NMR (CDCℓ 3 , δ): 0.86-1.12 (m, 12H), 1.36-1.48 (m, 9H), 1.77-2.05 (m, 1H), 3.40-3.78 (m, 5H), 4.82-4.92 (m, 1H), 5.24-5.42 (m, 1H), 5.67-5.74 (m, 2H), 5.98 (s, 1H), 7.25-7.50 (m, 5H) Example 20 Preparation of 2-((2S)-2-methoxycarbonylamino-3-methyl-1-hydroxybutyl)-3-phenylcyclopropenone 2,2-dimethyl-1,3-diyl acetal (Compound No. 161 in Table 1) IR (KBr, cm -1 ): 3436, 3378, 1858, 1792, 1703, 1626 NMR (CD 3 OD, δ): 0.88-1.35 (m, 12H), 1.90-2.15 (m, 1H), 3.55-3.90 (m, 8H), 4.95 (d, J=5.2Hz, 0.2H), 4.98 (d, J=5.0Hz, 0.8H), 7.32-7.55 (m, 3H), 7.60-7.83 (m, 2H) Example 21 Preparation of 2-[(2S)-2-((2S)-2-benzyloxycarbonylamino-3-methylvalerylamino)-1-hydroxyhexyl)-3-(4-fluorophenyl)cyclopropenone 2,2-dimethyl-1,3-propanediyl acetal (Compound No. 490 in Table 3) IR (KBr, cm -1 ): 3320, 1802, 1710, 1660, 1602 NMR (CD 3 OD, δ): 0.70-1.18 (m, 15H), 1.18-1.95 (m, 9H), 3.66-3.90 (m, 4H), 4.02-4.30 (m, 2H), 4.95 (m, 1H), 5.02 (s, 2H), 7.10-7.40 (m, 7H), 7.40-7.60 (m, 1H), 7.70-7.83 (m, 2H) Reference Example 22 Preparation of 2-((2S)-2-tert-butoxycarbonylamino-1-hydroxyhexyl) cyclopropenone To a solution of 8.80 g of 2-((2S)-2-tert-Butoxycarbonylamino-l-hydroxyhexyl) cyclopropenone 2,2-dimethyl-1,3-propanediyl acetal obtained in Example 5 in 100 mℓ of diethyl ether and 20 mℓ of tetrahydrofuran were added 0.2 mℓ of 2 N sulfuric acid and 1 mℓ of water, and the mixture was stirred for 30 minutes. After subsequent addition of 300 mℓ of ether, the resulting product was washed sequentially in 50 mℓ of an aqueous 0.01 N sodium hydroxide solution and an aqueous saturated brine. After drying over magnesium sulfate, the product was filtered and concentrated, followed by purification by silica gel column chromatography (eluent; hexane : ethyl acetate = 1 :2) to produce the objective product (3.15 g). Yield: 47 % IR (neat, cm -1 ): 3440, 1835, 1700 NMR (CDCℓ 3 , δ): 0.85-1.9 (m, 3H), 1.25-1.85 (m, 6H), 1.42 (s, 9H), 2.60-2.90 (m, 1H), 3.75-3.95 (m, 1H), 4.75-4.85 (m, 0.8H), 4.85-4.95 (m, 0.2H), 5.19 (d, J=9Hz, 1H), 8.59 (s, 0.8H), 8.65 (s, 0.2H) In the same manner as in Reference Example 22, the following compounds were produced. Example 23 Preparation of 2-((2S)-2-benzyloxycarbonylamino-1-hydroxyhexyl) cyclopropenone (Compound No. 190 in Table 2) IR (neat, cm -1 ): 3440, 3350, 1840, 1715 NMR (CDCℓ 3 , δ): 0.82-0.98 (m, 3H), 1.26-1.80 (m, 6H), 3.85-4.05 (m, 1H), 4.76-4.84 (m, 1H), 4.86-4.93 (m, 0.4H), 5.02-5.16 (m, 2.6H), 5.27 (d, J=7.8Hz, 0.4H), 5.47 (d, J=7.7Hz, 0.6H), 8.44 (s, 0.4H), 8.49 (s, 0.6H) Example 24 Preparation of 2-((2S)-2-tert-Butoxycarbonylamino-1-hydroxy-3-methylbutyl)-3-[(hydroxy)(phenyl)methyl]cyclopropenone (Compound No. 443 in Table 3) IR (neat, cm -1 ): 3440, 3330, 1845, 1716, 1683, 1630 NMR (CDCℓ 3 , δ): 0.96-1.11 (m, 6H), 1.18 (s, 1.9H), 1.37 (s, 1.0H), 1.39 (s, 3.6H), 1.43 (s, 2.5H), 1.90-2.15 (m, 1H), 3.68-3.78 (m, 0.3H), 3.78-3.89 (m, 0.7H), 4.89-5.40 (m, 1H), 5.16 (d, J=11Hz, 0.7H), 5.40 (d, J=11Hz, 0.3H), 5.30-5.41 (m, 1H), 5.62 (d, J=9.2Hz, 0.3H), 5.80 (d, J=9.2Hz, 0.7H), 5.86 (s, 1H), 7.50-7.86 (m, 3H), 7.86-8.11 (m, 2H) Example 25 Preparation of 2-((2S)-2-amino-1-hydroxyhexyl) cyclopropenone p-toluene sulfonate (Compound No. 179 in Table 2) To 5 mℓ of a dichloroethane solution of 150 mg of 2-((2S)-2-tert-butoxycarbonylamino-1-hydroxyhexyl) cyclopropenone obtained in Reference Example 22 was added 106 mg of p-toluene sulfonate monohydrate. After stirring at room temperature for 5 hours, the solvent was distilled off under reduced pressure to give 250 mg of the titled product. NMR (CD 3 OD, δ): 0.93-1.10 (m, 3H), 1.30-1.65 (m, 4H), 1.65-2.05 (m, 2H), 2.41 (s, 3H), 3.40-3.60 (m, 0.7H), 3.60-3.75 (m, 0.3H), 4.89 (d, J=4Hz, 0.7H), 5.15 (d, J=4Hz, 0.3H), 7.28 (d, J=8Hz, 2H), 7.74 (d, J=8Hz, 2H), 9.12 (s, 0.7H), 9.18 (s, 0.3H) Example 26 Preparation of 2-((2S)-2-amino-1-hydroxy-3-methylbutyl)-3-phenylcyclopropenone hydrochloride (Compound No. 272 in Table 2) To 8 mℓ of a dioxane solution of 3.12 g of 2-((2S)-2-tert-butoxycarbonylamino-1-hydroxy-3-methylbutyl)-3-phenylcyclopropenone 2,2-dimethyl-1,3-propanediyl acetal obtained in Example 1 was added 24 mℓ of a dioxane solution containing 4 N HCℓ, and the mixture was stirred for 20 minutes. The resulting crystal was filtered and washed with dioxane, to give 1.87 g of the titled product. Yield: 94 % IR (KBr, cm -1 ): 3200, 2975, 1855, 1618, 1510, 1450, 1055, 770, 690 NMR (CD 3 OD, δ): 1.21 (t, J=7Hz, 4.5H), 1.24 (t, J=7Hz, 1.5H), 2.0-2.2 (m, 0.25H), 2.2-2.4 (m, 0.75H), 3.38 (t, J=6Hz, 0.25H), 3.45 (t, J=6Hz, 0.75H), 5.21 (d, J=6Hz, 0.75H), 5.45 (d, J=6Hz, 0.25H), 7.60-7.80 (m, 3H), 8.10-8.20 (m, 2H) In the same manner as in Examples 37 and 38, the following compounds were produced. Example 27 Preparation of 2-((1S, 2S)-2-amino-1-hydroxy-4-methylpentyl)cyclopropenone p-toluene sulfonate (Compound No. 173 in Table 2) NMR (CD 3 OD, δ): 1.02 (d, J=6.2Hz, 3H), 1.06 (d, J=6.3Hz, 3H), 1.60-1.95 (m, 3H), 2.42 (s, 3H), 3.58 (m, 1H), 4.88 (d, J=4.9Hz, 1H), 7.31 (d, J=8.2Hz, 2H), 7.75 (d, J=8.2Hz, 2H), 9.11 (s, 1H) Example 28 Preparation of 2-((2S)-2-amino-1-hydroxy-3-phenylpropyl)cyclopropenone p-toluene sulfonate (Compound No. 200 in Table 2) NMR (CD 3 OD, δ): 2.41 (s, 3H), 3.03-3.30 (m, 2H), 3.80-4.10 (m, 1H), 4.75-5.00 (m, 1H), 7.15-7.45 (m, 7H), 7.75 (d, J=8.1Hz, 2H), 8.88 (s, 0.3H), 9.04 (s, 0.7H) Example 41 Preparation of 2-((2S)-2-amino-1-hydroxy-4-methylpentyl)-3-ethylcyclopropenone p-toluene sulfonate (Compound No. 220 in Table 2) NMR (CD 3 OD, δ): 0.95-1.15 (m, 6H), 1.55-1.95 (m, 3H), 2.41 (s, 3H), 2.68-2.88 (m, 2H), 3.40-3.60 (m, 1H), 4.75-4.85 (m, 1H), 7.27 (d, J=8.0Hz, 2H), 7.75 (d, J=8.0Hz, 2H) Example 29 Preparation of 2-((1S, 2S)-2-amino-l-hydroxyhexyl-3-((E)-1-hexenyl) cyclopropenone p-toluene sulfonate (Compound No. 252 in Table 2) IR (KBr, cm -1 ): 3422, 1845, 1630, 1601 NMR (CD 3 OD, δ): 0.80-1.05 (m, 6H), 1.20-1.95 (m, 10H), 2.36 (s, 3H), 2.32-2.40 (m, 2H), 3.25-3.45 (m, 1H), 4.82 (d, J=7.3Hz, 1H), 6.38 (d, J=16Hz, 1H), 7.02 (dd, J=16Hz, 7.0Hz, 1H), 7.24 (d, J=8.0Hz, 2H), 7.70 (d, J=8.0Hz, 2H) Example 30 Preparation of 2-((1S, 2S)-2-amino-1-hydroxyhexyl)-3-((Z)-1-hexenyl) cyclopropenone p-toluene sulfonate (Compound No. 258 in Table 2) IR (neat, cm -1 ): 3260, 1845, 1633 NMR (CDCℓ 3 , δ): 0.73 (t, J=7.1Hz, 3H), 0.89 (t, J=6.7Hz, 3H), 1.08-1.95 (m, 10H), 2.35 (s, 3H), 2.40-2.65 (m, 2H), 3.33 (m, 1H), 3.92 (s, 3H), 4.88 (m, 1H), 6.21 (d, J=10Hz, 1H), 6.40 (dd, J=10Hz, 6.8Hz, 1H), 7.14 (d, J=6.7Hz, 2H), 7.71 (d, J=6.7Hz, 2H), 7.81 (m, 1H) Example 31 Preparation of 2-((2S)-1-hydroxy-3-methyl-2-methylaminobutyl)-3-phenylcyclopropenone hydrochloride (Compound No. 282 in Table 2) IR (KBr, cm -1 ): 3422, 1858, 1626 NMR (CD 3 OD, δ): 0.78-0.95 (m, 6H), 2.05-2.40 (m, 1H), 2.79 (s, 3H), 3.47 (m, 1H), 5.28 (d, J=4.5Hz, 0.5H), 5.43 (d, J=4.4Hz, 0.5H), 7.55-7.75 (m, 3H), 7.95-8.13 (m, 2H) Example 32 Preparation of 2-(2-amino-1-hydroxy-2-methylpropyl)-3-phenylcyclopropenone hydrochloride (Compound No. 298 in Table 2) IR (KBr, cm -1 ): 3300, 3250, 1858, 1620 NMR (CD 3 OD, δ): 1.42 (s, 3H), 1.57 (s, 3H), 4.98 (s, 1H), 7.55-7.78 (m, 3H), 8.07 (d, J=7.3Hz, 2H) Example 33 Preparation of 2-((2S)-2-amino-1-hydroxy-3-methylbutyl)-3-(1-hydroxy-1-methylethyl) cyclopropenone hydrochloride (Compound No. 428 in Table 2) IR (KBr, cm -1 ): 3420, 1846, 1615 NMR (CD 3 OD, δ): 1.09 (d, J=6.9Hz, 2.1H), 1.13 (d, J=6.9Hz, 2.1H), 1.14 (s, 1.8H), 1.56 (s, 4.2H), 1.58 (s, 1.8H), 1.99 (m, 0.3H), 2.15 (m, 0.7H), 3.25 (m, 0.3H), 3.39 (m, 0.7H), 5.01 (d, J=5.5Hz, 0.7H), 5.19 (d, J=4.5Hz, 0.3H) Example 34 Preparation of 2-((2S)-2-amino-1-hydroxy-3-methylbutyl)-3-(4-fluorophenyl) cyclopropenone (Compound No. 314 in Table 2) IR (KBr, cm -1 ): 3280, 1858, 1620, 1600 NMR (CD 3 OD, δ): 1.05-1.33 (m, 6H), 2.07 (m, 0.2H), 2.29 (m, 0.8H), 3.38 (m, 0.2H), 3.44 (m, 0.8H), 5.20 (d, J=6.1Hz, 0.8H), 5.41 (d, J=4.7Hz, 0.2H), 7.38-7.52 (m, 2H), 8.15-8.32 (m, 2H) Example 35 Preparation of 2-((2S)-2-amino-1-hydroxy-3-methylbutyl)-3-[(hydroxy)(phenyl)methyl]cyclopropenone hydrochloride (Compound No. 444 in Table 2) IR (KBr, cm -1 ): 3430, 1846, 1626 NMR (CD 3 OD, δ): 1.0-1.20 (m, 6H), 1.90-2.22 (m, 1H), 3.20-3.45 (m, 1H), 5.0-5.25 (m, 1H), 5.97 (s, 0.75H), 6.0 (s, 0.25H), 7.28-7.45 (m, 3H), 7.45-7.60 (m, 2H) Example 36 Preparation of 2-((2S)-2-methoxycarbonylamino-3-methyl-1-hydroxybutyl)-3-phenylcyclopropenone (Compound No. 278 in Table 2) IR (neat, cm -1 ): 3333, 1856, 1705, 1622 NMR (CDCℓ 3 , δ): 0.95-1.15 (m, 6H), 1.95-2.40 (m, 1H), 3.56 (s, 2.4H), 3.63 (s, 0.6H), 3.72 (m, 0.2H), 3.80 (m, 0.8H), 5.09 (d, J=4.5Hz, 1H), 5.72 (d, J=6.7Hz, 1H), 7.45-7.60 (m, 3H), 7.93-8.08 (m, 2H)

Claims: Cyclopropene derivatives represented by the general formula (I): [In the above general formula (I), R 1 represents a hydrogen atom or a protective group of the amino group; R 2 represents a hydrogen atom, a protective group of the amino group or C 1 -C 5 alkyl group; or when R 1 and R 2 are taken together. they represent a phthaloyl group; R 4 and R 6 independently represent hydrogen atoms or C 1 -C 5 alkyl groups; R 3 and R 5 independently represent hydrogen atoms or C 1 -C 15 alkyl groups optionally substituted with a C 3 -C 10 cycloalkyl group or a C 6 -C 10 aryl group; or when R 5 and R 6 are taken together, they represent a C 2 -C 6 alkylene group; R 7 and R 8 represent -OR 10 and -OR 11 , respectively (wherein R 10 and R 11 independently represent C 1 -C 5 alkyl groups optionally substituted with a phenyl group; or when R 10 and R 11 are taken together, they represent a C 2 -C 6 alkylene group optionally substituted with one or more C 1 -C 5 alkyl groups); or when R 7 and R 8 are taken together, they represent =O; R 9 represents a hydrogen atom, a C 1 -C 15 alkyl group, a C 3 -C 10 cycloalkyl group, a C 2 -C 15 alkenyl group, a C 6 -C 10 aryl group optionally substituted with a substituent, a heterocyclic group optionally substituted with a substituent, or -CR 12 R 13 OH (wherein R 12 and R 13 independently represent hydrogen atoms, C 1 -C 15 alkyl groups or C 6 -C 10 aryl groups; or R 12 and R 13 taken together form a C 3 -C 10 cycloalkyl group); and n represents 0 or 1, provided that when n represents 1, R 7 , when taken together with R 8 does not represent =O and further provided that when R 1 represents a tert-butoxycarbonyl group and n represents 0. R 7 and R 8 when taken together do not represent =O or a 2.2-dimethyl-propylenedioxy group] and the salts thereof. The compounds according to claim 1, wherein R 9 represents a hydrogen atom; a C 1 -C 15 alkyl group; a C 3 -C 10 cycloalkyl group; a C 2 -C 15 alkenyl group; a C 6 -C 10 aryl group optionally substituted with one or more substituents selected from the group consisting of halogen atoms. C 1 -C 5 alkyl groups, hydroxyl groups and C 1 -C 5 alkoxy groups; a heterocyclic group having one to four hetero atoms selected from the group consisting of oxygen atoms, sulfur atoms and nitrogen atoms with the total number of the atoms constituting the ring being in the range of from 5 to 10, and optionally substituted with one or more substituents selected from the group consisting of C 3 -C 12 trioalkylsilyl groups, halogen atoms, C 1 -C 5 alkyl groups, hydroxyl groups and C 1 -C 5 alkoxy groups; or -CR 12 R 13 OH (wherein R 12 and R 13 independently represent hydrogen atoms, C 1 -C 15 alkyl groups or C 6 -C 10 aryl groups or when R 12 and R 13 are taken together form a C 3 -C 10 cycloalkyl group). The compounds according to claim 1, wherein R 1 represents a hydrogen atom, a tert-butoxycarbonyl group, a benzyloxycarbonyl group, a methoxycarbonyl group, a 9-fluorenylmethoxycarbonyl group, a p-toluene sulfonyl group, or a trityl group; R 2 , R 4 and R 6 independently represent hydrogen atoms or C 1 -C 3 alkyl groups; or when R 1 and R 2 are taken together, they represent a phthaloyl group; R 3 and R 5 independently represent hydrogen atoms or C 1 -C 5 alkyl groups optionally substituted with a C 3 -C 8 cycloalkyl group, a phenyl group or a naphthyl group; or R 5 , when taken together with R 6 represents a C 2 -C 5 alkylene group; R 7 and R 8 represent -OR 10 and -OR 11 , , respectively (wherein R 10 and R 11 independently represent C 1 -C 3 alkyl groups optionally substituted with a phenyl group; or R 10 when taken together with R 11 represents a C 2 -C 4 alkylene group optionally substituted with one or more C 1 -C 3 alkyl groups; or R 7 , when taken together with R 8 represents =0; R 9 represents a hydrogen atom; a C 1 -C 6 alkyl group; a C 3 -C 8 cycloalkyl group; a C 2 -C 8 alkenyl group; a phenyl group or a napthyl group each optionally substituted with one or more substituents selected from the group consisting of halogen atoms, C 1 -C 5 alkyl groups and C 1 -C 5 alkoxy groups; heterocyclic groups having one to four hetero atoms selected from the group consisting of oxygen atoms, sulfur atoms and nitrogen atoms with the total number of the atoms constituting the ring being in the range of from 5 to 10, and optionally substituted with one or more substituents selected from the group consisting of halogen atoms, C 1 -C 5 alkyl groups, C 1 -C 5 alkoxy groups, and C 3 -C 12 trialkylsilyl groups; or -C 12 R 13 OH (wherein R 12 and R 13 independently represent hydrogen atoms, C 1 -C 3 alkyl groups or phenyl groups). The compounds according to claim 1, wherein R 1 represents a hydrogen atom, a tert-butoxycarbonyl group, a benzyloxycarbonyl group or a methoxycarbonyl group; R 2 , R 4 and R 6 independently represent hydrogen atoms or C 1 -C 3 alkyl groups; R 3 and R 5 independently represent hydrogen atoms or C 1 -C 5 alkyl groups optionally substituted with a phenyl group; R 7 and R 8 represent -OR 10 and -OR 11 , respectively (wherein R 10 , when taken togetherwith R 11 represents a C 2 -C 4 alkylene group optionally substituted with one or more C 1 -C 3 alkyl groups; or R 7 , when taken together with R 8 represents =0; R 9 represents a hydrogen atom; a C 1 -C 6 alkyl group: a C 2 -C 8 alkenyl group; a phenyl group optionally substituted with one or more substituents selected from the group consisting of halogen atoms and C 1 -C 5 alkyl groups; a furyl group or a thienyl group each optionally substituted with one or more C 3 -C 12 trialkylsilyl groups; or -CR 12 R 13 OH (wherein R 12 and R 13 independently represent hydrogen atoms, C 1 -C 3 alkyl groups or phenyl groups).

Inventors: ANDO RYOICHI, MORINAKA YASUHIRO, NAKAMURA EIICHI, ANDO, RYOICHI, MORINAKA, YASUHIRO, NAKAMURA, EIICHI
Applicants: MITSUBISHI CHEM CORP, MITSUBISHI CHEMICAL CORPORATION
Application year: 1993
Main classification: C07D317
IPC codes: C07D319, C07F7