JPH0528713B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION (Technical Field of the Invention) The present invention relates to a stereoselective method for synthesizing optically active (+)-pedamide, which is a fragment compound of Pederin. (Background of the invention) Paederus
Pederin, isolated from Fuscipes Curtis, has been subjected to many synthetic studies due to its unique three-dimensional structure and physiological activity. For example, as for physiological activity, Lupinus
albus) and onion (Allium cepa), it causes chromosomal mutations especially during the metaphase of cell division.
In addition, a growth inhibiting effect on Trichomonas is observed. What is even more interesting is that it shows an inhibitory effect on the growth of white rat sarcoma (sarcoma 180) (see Nankodo Publishing, ``Physiologically Active Substances of Insects'' by Shojiro Ishii, published on November 11, 1962). It is considered that the most efficient method for synthesizing pederin is to first synthesize the right and left halves of pederin and then combine them. The right half of this is called pedamide (H. Yanagiya et al.
Tetrahedron Lett., 23 , 4039 (1982)). Conventionally, the above-mentioned pedamides have been synthesized using optically active acetal ketones as starting materials, but a more efficient method for synthesizing pedamides for large-scale synthesis has been desired. (Objective of the Invention) An object of the present invention is to provide a method for stereoselectively synthesizing pedamide, which is a fragment compound of pederin having a unique steric structure and physiological activity, with high optical yield and high reaction yield. It is in. (Structure of the Invention) <Synthesis of Starting Material> The starting material (1) of the present invention can be obtained from commercially available optically active l-malic acid by, for example, the following process [H. Hayashi et al J. Am. Chem.Soc., 95 ,
8749 (1973); K.Mori et al, Tetrahedron, 35 ,
933 (1979); S.Hanessian et al, J.Org.Chem.,
48, 4427 (1983)]. <Synthesis of target compound> The obtained starting material (1) is reacted with LDA (lithium diisopropylamine) and (CH ₃ ) ₂ CHCOOEt to obtain β-hydroxy ester (2). A suitable solvent is tetrahydrofuran (THF).
The reaction temperature and reaction time were -40 to 78℃, respectively.
0.5 to 5 hours is appropriate. The obtained β-hydroxy ester (2) is treated with an acid to decompose the acetal moiety. The acid used is p-
Suitable are toluenesulfonic acid (p-TsOH), methanesulfonic acid (MsOH), and camphorsulfonic acid.
Reflux for ~4 hours. Subsequently, it is reacted with t-butyldiphenylsilyl chloride ( ^tBuPh ₂ SiCl) in the presence of imidazole. This reaction is carried out in dimethylformamide.
The reaction is carried out for 3-6 hours at room temperature. Further, acid treatment is performed to cyclize and form the lactone.
(3) is obtained. The acids used are camphorsulfonic acid (CSA),
Concentrated sulfuric acid, polyphosphoric acid, etc. are suitable. The obtained lactone (3) is reacted with ethyl vinyl ether in the presence of an acid catalyst to obtain an ethoxyethyl (EE) compound (4). As the acid catalyst, pyridinium p-toluenesulfonate (PPTS), camphorsulfonic acid, toluenesulfonic acid, etc. are suitable. Solvent: methylene chloride, dichloroethane,
Ether etc. are suitable. The appropriate reaction temperature and reaction time are 0° C. to room temperature and 0.5 to 3 hours, respectively. The obtained ethoxyethyl compound (4) was subjected to LDA and
Reaction with CH ₃ COO ^t Bu gives hemiacetal (5). The optimal solvent is THF, and the reaction temperature,
The appropriate reaction time is -78 to -40°C and 0.5 to 5 hours. The obtained hemiacetal (5) is
By reacting with orthoformic acid ester, CSA, 4α-
Alcohol and 4β-alcohol (7) are obtained. Suitable solvents include methanol-methylene chloride, methanol, and the like. The reaction temperature and reaction time are, respectively,
A suitable time is room temperature for 0.5 to 5 hours. 4α-Alcohol (6) is oxidized to ketone (8) using pyridinium chlorochromate (PCC) and molecular sieves, which is converted to k-selectride [formula] and L-selectride [formula]. 4β-alcohol (7) can be obtained by selective reduction using The obtained 4β-alcohol (7) was
React with ethanediol in the presence of Lewis acid,
β-Thioacetal-δ-lactone (9) is obtained. Obtained β-thioacetal-δ-lactone (9)
is treated with a methylating agent to obtain dimethoxy compound (10). As the methylating agent, diazomethane-ether is preferably used in the presence of silica gel. In addition,
Reaction temperature and reaction time were 0°C to room temperature, 1
~6 hours is appropriate. The obtained dimethoxy compound (10) is reduced to obtain lactol (11). As the reducing agent, diisobutyl aluminum hydride (DIBAH) and triethoxylithium aluminum hydride (LAH(OEt) ₃ ) are suitable. Suitable solvents are toluene, xylene, ether, etc., and the reaction temperature and reaction time are -78 to -78, respectively.
A suitable time is 0°C for 0.5 to 5 hours. The obtained lactol (11) was treated in the presence of a base.
Reaction with BrCH ₂ OCH ₃ gives methoxymethyl ether (12). Diisopropylethylamine and dimethylaniline are suitable as the base. The reaction is carried out at reflux for 12-24 hours. The obtained methoxymethyl ether (12) is dethioacetalized to obtain dimethoxyketone (13). As the dethioacetalizing agent, N-bromsuccinimide (NBS) _-AgNO3 / _CH3CN -water,
CuCl ₂ /CuO/acetone and the like are preferably used.
In the former case, the reaction conditions are preferably 0°C and 15 minutes to 1 hour, and in the latter case, refluxing is preferably carried out for 1 to 3 hours. The obtained dimethoxy ketone (13) is reduced to obtain dimethoxy alcohol (14). LiAlH ₄ , LiBH ₄ , NaBH ₄ is used as the reducing agent, and ether, THF, methanol, etc. are suitable as the solvent. The appropriate reaction temperature and reaction time are -20°C to room temperature and 0.5 to 3 hours, respectively. The obtained dimethoxy alcohol (14) is benzoylated to obtain benzoate (15). A suitable benzoylating agent is benzoyl chloride-pyridine. This reaction may be stirred at room temperature for 6 to 18 hours. The obtained benzoate (15) is heated under acidic conditions to demethoxymethyl etherify it. Suitable acidic conditions are THF-dilute HCl and dioxane-dilute HCl systems. The reaction temperature and reaction time are, respectively,
A suitable time is 30 to 60°C for 1 to 4 hours. Then, without separation, acetylation is performed to obtain the acetyl compound (16). As the acetylating agent, Ac ₂ O-pyridine,
AcCl-pyridine is preferred; at room temperature, 6 to 18
If you leave it for a while, the reaction will proceed. The obtained acetyl compound (16) was treated in the presence of Lewis acid,
React with (CH ₃ ) ₃ SiCN to obtain nitrile (17). As the Lewis acid, _BF3 -ether and _SnCl2 are suitable. Also, suitable solvents are CH ₂ Cl ₂ and ClCH ₂ CH ₂ Cl. The reaction temperature and reaction time are 0, respectively.
C. to room temperature for 2 to 5 hours. The obtained nitrile (17) is hydrolyzed to obtain the desired (+)-pedamide (t). Hydrolysis is performed using a Lewis acid, e.g. TICl ₄ −
It is sufficient to use a specific AcOH solution system. In this case, it may be stirred at room temperature for 12 to 18 hours. Hydrolysis can also be carried out using H ₂ O ₂ -K ₂ CO ₃ -ethanol, but in this case, the reaction temperature and reaction time are preferably 0 to 20°C and 5 to 18 hours, respectively. Thus, we obtain the desired (+)−pedamide(t), but
An example of the process of the present invention is shown below. The present invention will be explained below with reference to Examples.
The present invention is not limited to these in any way. In addition, the obtained compounds (2), (3), (4), (5), (6),
(7), (8), (9), (10), (11), (12), (13), (14), (15)
, (16), (17)
is a new compound. Example 1 A solution of 25.4 ml of diisopropylamine in 170 ml of anhydrous tetrahydrofuran at -20°C under a stream of argon.
A 1.6N-BuLi-hexane solution (107.4 ml) was added dropwise and stirred at 0°C for 30 minutes, then 24 ml of ethyl isobutyrate was added dropwise at -78°C, and the mixture was stirred at the same temperature for 25 minutes. Furthermore, a solution of 11.8 g of aldehyde (1) in 110 ml of anhydrous tetrahydrofuran was added dropwise, and the mixture was stirred at the same temperature for 40 minutes. After the reaction, saturated NaHCO ₃ aqueous solution was added, the mixture was returned to room temperature, extracted with ether, and the ether layer was washed with saturated brine and dried over MgSO ₄ . When the solvent is distilled off, β
15.85 g (74.4%) of -hydroxyester (2) are obtained. [Physical properties of compound (2)] NMR (CDCl ₃ ): δ 1.16, 1.18, 1.20, 1.36, 1.37, 1.41, 1.42
(eachs; Me) 1.266, 1.271 (eacht, J = 7.1Hz; 2XEt) 2.87 (α, J = 5.9Hz; OH) 3.34 (α, J = 2.9Hz; OH) IR (neat): 3500, 1725cm ^-1 Example 2 β-hydroxy ester (2) 320 mg methanol
Add 19 mg of p-TsOH to 10 ml solution and reflux for 1 hour.
42 mg of imidazole was added under ice-cooling, and the mixture was stirred at room temperature for 10 minutes. After adding benzene and concentrating under reduced pressure, dimethylformamide 5ml, imidazole 293mg, ^t
576μ of BuPh ₂ SiCl was added and stirred at room temperature for 30 minutes. After the reaction, add ether, wash with saturated saline,
Dry with _MgSO4 . After evaporating the solvent, the residue was applied to a silica gel flash column (ether:hexane=1:
1 to 3:1) to obtain 390 mg of the silyl compound. This was directly dissolved in 20 ml of benzene, 40 mg of camphorsulfonic acid (CSA) was added, and the mixture was stirred at room temperature for 12 hours. After the solvent was distilled off, benzene was added and the solvent distillation was repeated, then benzene was added and the mixture was stirred at room temperature for 10 hours. After the reaction, add saturated NaHCO ₃ aqueous solution, extract with ether,
The ether layer was washed with saturated NaHCO ₃ aqueous solution and saturated brine, and then dried with MgSO ₄ . After evaporation of the solvent, 365 mg (72%) of lactone (3) was obtained. [Physical properties of compound (3)] NMR (CDCl ₃ ): δ 1.057, 1.062 (eachs; 2×Bu ^t ) 1.315, 1.350, 1.353 (eachs; Me) 4.43, 4.74 (eachm; 2×C-2βH) IR (CHCl ₃ ): 3600, 3420, 1720 cm ^-1 Example 3 In a solution of 12.45 g of lactone (3) in 100 ml of methylene chloride
Add 5.74 ml of CH ₂ =CH-OEt and 0.6 g of pyridinium-p-toluenesulfonic acid (PPTS) and leave at room temperature 1.
Stir for hours. After the reaction, saturated aqueous NaHCO ₃ solution was added and extracted with ether. After washing the ether layer with saturated brine, MgSO ₄
It was dried. When the solvent is distilled off, the ethoxyethyl compound (4)
14.93g was obtained. This was directly subjected to the next reaction. [Physical properties of compound (4)] IR (neat): 1735 cm ^-1 Example 4 A solution of 13.4 ml of diisopropylamine in 90 ml of anhydrous tetrahydrofuran at -20°C under a stream of argon.
Add 58.2ml of 1.58NBuLi-hexane solution dropwise and heat to 0°C.
The mixture was stirred for 30 minutes. Then CH ₃ COO ^t at −78℃
12.7 ml of Bu was added dropwise and stirred at the same temperature for 45 minutes. Ethoxyethyl form (4) 14.86g of anhydrous tetrahydrofuran
60 ml of the solution was added dropwise and stirred at the same temperature for 30 minutes. After the reaction, add saturated NaHCO ₃ aqueous solution, return to room temperature, extract with ether, and saturate the ether layer.
After washing with NaHCO ₃ aqueous solution and saturated saline, MgSO ₄
It was dried. When the solvent is distilled off, hemiacetal (5)
18.66g was obtained. This was directly subjected to the next reaction. [Physical properties of compound (5)] IR (neat): 3430, 1735, 1705 cm ^-1 Example 5 22.3 ml of methyl orthoformate was added to a solution of 18.57 g of hemiacetal (5) in 150 ml of methylene chloride-methanol (1:1). , 1.2 g of camphor sulfonic acid was added, and the mixture was stirred at room temperature for 1.5 hours. After the reaction, saturated aqueous NaHCO ₃ solution was added and extracted with ether. The ether layer was washed with saturated brine and dried over MgSO ₄ . After distilling off the solvent, silica gel flash column chromatography (hexane:ether = 4:1 to 3:2) yielded 6.12 g (37.8%, lactone) of 4β-alcohol (7).
(3)) and 6.04 g (37.2%, from lactone (3)) of 4α-alcohol (6) were obtained. [Physical properties of compound (6)] NMR (CDCl ₃ ): δ 1.05 (s; ^t Bu) 1.10, 1.16 (eachs; 2×Me) 1.46 (s; CO ₂ ^t Bu) 3.40 (s; OMe) 3.45 (dt, J = 10.0, 2.9 Hz; C-4α H) IR (neat): 3520, 1725 cm ^-1 [α] ¹⁸ _D -9.2° (C = 1.94, CHCl ₃ ) [Physical properties of compound (7) ] NMR (CDCl ₃ ): δ 1.02, 1.04 (eachs; 2×Me) 1.05 (s; ^t Bu) 1.45 (s; CO ₂ ^t Bu) 3.29 (s; OMe) 3.98 (dd, J=11.8, 4.8Hz ; C-4β H) IR (neat): 3450, 1725 cm ^-1 [α] ¹⁹ _D +5.4° (C = 2.12, CHCl ₃ ) Example 6 Pyridinium chlorochromate (PCC) 740
mg, 3A-Molecular sieves powder 860mg in methylene chloride 20ml suspension 4α-alcohol (6) 620
A solution of 10 mg of methylene chloride in 10 ml was added dropwise, and the mixture was stirred at room temperature for 1 hour. After the reaction, ether was added and subjected to Florisil column chromatography (ether) to obtain 622 mg (100 mg) of ketone (8).
%)was gotten. [Physical properties of compound (8)] NMR (CDCl ₃ ): δ 1.06 (s; ^t Bu) 1.11, 1.30 (eachs; 2×Me) 1.45 (s; COO ^t Bu) 3.30 (s; OMe) IR ( neat): 1720cm ^-1 [α] ²⁰ _D -10.7゜ (C = 1.46, CHCl ₃ ) Example 7 L-selectride (1M-THF solution) in a solution of 90 mg of ketone (8) in 4 ml of anhydrous tetrahydrofuran at -78°C 0.83 ml was added dropwise and stirred at the same temperature for 4 hours. After the reaction, water was added and the mixture was returned to room temperature, extracted with ether, and the ether layer was washed with saturated brine and dried over MgSO ₄ . After evaporating the solvent, it was subjected to silica gel flash column chromatography (hexane:ether = 3:1).
81 mg (89.7%) of 4β-alcohol (7) was obtained. NMR and IR were consistent with the standard 4β-alcohol (7). Example 8 Add 4 ml of 1,2-ethanedithiol to 260 mg of 4β-alcohol (7) and BF ₃ − at -30° under an argon stream.
0.26 ml of Et ₂ O was added dropwise and stirred at -30 to -25°C for 3 hours. After the reaction, the solvent was distilled off under reduced pressure, and the residue was subjected to silica gel preparative thin layer chromatography (ethyl acetate) to obtain the lactone.
(9) 116 mg (82.8%) was obtained. [Physical properties of compound (9)] NMR (CDCl ₃ ): δ 119, 1.26 (each s; Me x 2) 4.05 (m; C-2 H) 4.54 (dd, J = 10.0, 2.4 Hz; C = 4βH) IR (CHCl ₃ ): 3570, 3450, 1735 cm ⁻¹ Example 9 A 400 ml solution of diazomethane-ether was prepared from 25.2 g of N-methyl-N-nitrosourea. To a solution of 1.02 g of lactone (9) in 100 ml of ether was added 4 g of silica gel (Wakogel C-200) in 80 ml of a diazomethane-ether solution, and the mixture was stirred at 0°C for 30 minutes. Furthermore, silica gel and diazomethane were added, and this operation was repeated a total of 4 times. Finally, 40 ml of diazomethane was added, stirred for 30 minutes at 0°C, washed with filtrate and ether, distilled off the solvent, and subjected to silica gel flash column chromatography (hexane:ether = 1:3, ether) to yield 870 mg (77.8%) of the dimethoxy compound (10). ) and monomethyl form
91.9 mg (8.6%) was obtained. The monomethyl compound was methylated again to obtain 58.6 mg (5.3%) of dimethoxy compound (10). The total amount was 928.6 mg (83.1%). [Physical properties of compound (10)] NMR (CDCl ₃ ): δ 1.18, 1.25 (each s; 2 × Me) 3.40, 3.41 (each s; 2 × OMe) 3.64 (m; C-2 H) 4.39 ( dd, J = 10.5, 1.5Hz; C-4βH) IR (neat): 1735cm ^-1 α19D + 96.1° (C = 1.40, CHCl ₃ ) Example 10 Lactone (10) 1.513g at -78℃ under argon stream 5.4 ml of diisobutylaluminum hydride (1.76M in hexane) in 70 ml of anhydrous toluene solution.
was added dropwise and stirred at the same temperature for 45 minutes. After the reaction, 3.5 ml of isopropanol was added dropwise, the temperature was returned to room temperature, 2 ml of water was added, and after stirring at room temperature for 20 minutes, MgSO ₄ and silica gel were added, filtered, washed with ether, and the solvent was distilled off to obtain 1.431 g (94.0%) of lactol (11). [Physical properties of compound (11)] NMR (CDCl ₃ ): δ 1.09, 1.17 (each s; 2×Me) 3.399, 3.403 (each s; 2×OMe) IR (neat): 3400 cm ^-1 Example 11 To a solution of 38 mg of lactol (11) in 3 ml of methylene chloride were added 0.3 ml of diisopropylethylamine and 0.1 ml of BrCH ₂ OMe, and the mixture was refluxed for 4.5 hours. After the reaction, a saturated aqueous NaHCO ₃ solution was added and extracted with ether. The ether layer was washed with a saturated aqueous NaHCO ₃ solution and saturated brine, and then dried over MgSO ₄ . When the solvent was distilled off using benzene azeotropy, 40.7 mg (94.2 mg) of acetal (12) was obtained.
%)was gotten. [Physical properties of compound (12)] NMR (CDCl ₃ ): δ 1.09, 1.17 (each s; 2×Me) 3.386, 3.398, 3.403 (eachs; 3×OMe) 4.61, 4.96 (eachd, J=6.6Hz ; OCH ₂ O) 4.81 (dd, J = 9.8, 2.2 Hz; C-8βH) IR (neat): 1035, 1100, 1145 cm ^-1 Example 12 AgNO ₃ 4.04 in NaCO ₃ aqueous solution (1.26 g/6 ml)
24 ml of acetonitrile solution was added thereto and stirred at room temperature for 15 minutes, and then 3.84 g of N-bromo-succinimide (NBS) was added at 0°C and stirred for 5 minutes. A solution of 1.315 g of acetal (12) in 12 ml of acetonitrile at 0°C,
Next, 3 ml of water was added and stirred at 0°C for 30 minutes. After the reaction, 15 ml of saturated aqueous Na ₂ SO ₃ solution and 50 ml of hexane-methylene chloride (1:1) were added, filtered through Celite, washed with ether, and the liquid and washings were combined.
After washing with saturated aqueous NaHCO ₃ solution, it was dried with MgSO ₄ . After evaporation of the solvent, 906 mg (87%) of ketone (13) was obtained. [Physical properties of compound (13)] NMR (CDCl ₃ ): δ 1.01, 1.14 (each s; 2×Me) 3.37, 3.39, 3.40 (each s; 3×OMe) 4.64, 5.03 (eachd, J=6.6 Hz; OCH ₂ O) 4.85 (dd, J = 9.8, 2.9Hz; C-8βH) IR (neat): 1710 cm ^-1 Example 13 A solution of 884 mg of ketone (13) in 50 ml of anhydrous ether at 0°C
Then, 347 mg of LiAlH ₄ was added and stirred for 30 minutes. water after reaction
Add 0.35ml, 15% NaOH0.35ml, _H2O1.05ml ,
The mixture was stirred at room temperature for 20 minutes. After adding MgSO ₄ and distilling off the solvent, 873 mg (98.1%) of alcohol (14) was obtained. [Physical properties of compound (14)] NMR (CDCl ₃ ): δ 0.89, 0.93 (each s; 2×Me) 3.375, 3.384, 3.396 (each s; 3×OMe) 4.60, 4.98 (each d, J= 6.6Hz; OCH ₂ O) 4.66 (dd, J = 10.0, 2.4Hz; C-8βH) IR (neat): 3450cm ^-1 Example 14 Add 427 μ of benzoyl chloride to a 2 ml solution of pyridine containing 215 mg of alcohol (14) at room temperature 14 Stir for hours. After the reaction, ether was added, and the mixture was washed with water, saturated NaHCO ₃ aqueous solution, 2% HCl, saturated NaHCO ₃ aqueous solution, and saturated brine, and then dried over MgSO ₄ . After distilling off the solvent, silica gel flash column chromatography (hexane:ether = 1:2 to 1:3) yields benzoate.
(15) 291.8 mg (100%) was obtained. [Physical properties of compound (15)] NMR (CDCl ₃ ): δ 0.90, 1.13 (each s; 2×Me) 3.388, 3.394, 3.398 (each s; 3×OMe) 4.61, 5.00 (each d, J= 6.6Hz; OCH ₂ O) 4.80 (dd, J=10.0, 2.4Hz; C-8βH) 4.93 (dd, J=12.0, 4.6Hz; C-6βH) IR (neah); 1720cm ^-1 [α] ²⁰ _D −57.2° (C=1.74, CHCl ₃ ) Example 15 Benzoate (15) 114 mg of tetrahydrofuran 10
ml solution was added with 1.5 ml of 6N-HCl and heated at 50°C for 2 hours. After extraction with ether and ethyl acetate, washing with saturated brine, saturated NaHCO ₃ aqueous solution, and saturated brine
Dry with _MgSO4 . After evaporating the solvent, 1 ml of pyridine and 1 ml of acetic anhydride were added to the residue, and the mixture was left at room temperature for 12 hours.
After distilling off the solvent using benzene azeotrope, silica gel flash column chromatography (hexane:ether = 2:3~
1:3), 98 mg of acetate (16) was obtained. It is a mixture of α-OAc form and β-OAc form = 2:1. [Physical properties of compound (16)] NMR (CDCl ₃ ): δ 0.92, 1.14 (each s; 2×Me) 0.95, 1.11 (each s; 2×Me) 2.11, 2.15 (each s; 2×OMe) 3.38, 3.39 (each s; 2 x OMe) 3.37, 3.38 (each s; 2 x OMe) IR (neat): 1755, 1720 cm ^-1 Example 16 Me ₃ 600μ of SiCN and 1.4μ of BF ₃ ·Et ₂ O were added dropwise and stirred for 3 hours. After the reaction, a saturated aqueous NaHCO ₃ solution was added and extracted with ether. The ether layer was washed with a saturated aqueous NaHCO ₃ solution and dried over MgSO ₄ . After evaporation of the solvent, 236 mg (94%) of nitrile (17) was obtained by silica gel flash column chromatography (hexane: ethyl acetate = 2:1).
was gotten. It is a mixture of β-CN:α-CN=10:1. [Physical properties of compound (17)] NMR (CDCl ₃ ): δ 0.98, 1.11 (each s; 2×Me) 0.92, 1.14 (each s; 2×Me) 3.408, 3.413 (each s; 2×OMe) 3.393, 3.402 (each s; 2×OMe) 4.96 (dd, J=6.1, 1.7Hz; C-8αH) 4.38 (dd, J=12.2, 2.9Hz; C-8βH) IR (neat): 1720cm ^-1 implementation Example 17 TiCl ₄ 0.33 in a solution of 178.3 mg of nitrile (17) in 3.6 ml of acetic acid
0.16 ml of water was added and stirred at room temperature for 15 hours. The reaction solution was poured into a saturated NaHCO ₃ aqueous solution, ethyl acetate was added thereto, the mixture was filtered through Celite, and the ethyl acetate layer was washed with saturated brine and dried over MgSO ₄ . After evaporation of the solvent, preparative thin layer chromatography on silica gel (developed three times with ethyl acetate) yielded (+)-pedamide (18).
162.1 mg (86.6%) and epipedamide (19) 18.8 mg (10
%)was gotten. [Physical properties of (+)-pedamide (18)] NMR (CDCl ₃ ): δ 0.93, 1.08 (each s; 2×Me) 3.39, 3.42 (each s; 2×OMe) 4.48 (dd, J=6.6 , 2.7Hz; C-8αH) 4.98 (dd, J=10.7, 4.6Hz; C-6βH) IR (Nujol): 3445, 3340, 1720, 1685cm ^-1 [α] ²² _D +20.5゜ (C=3.22 , CHCl ₃ ) mp145−6° (from Et ₂ O-hexane) Elemental analysis values: Calculated value C, 63.31, H, 7.70, N, 3.69 Actual value C, 63.16, H. 7.67, B, 3.75 [Epipedamide (19 )] NMR (CDCl ₃ ): δ 0.92, 1.10 (each s; 2×Me) 3.39, 3.41 (each s; 2×OMe) 4.02 (dd, J=12.2, 2.7Hz; C-8βH) 5.01 (dd, J=11.7, 4.9Hz; C-6βH)

Claims (1)

[Claims] 1 Structural formula: Using a compound represented by as a starting material, the compound is treated in the presence of lithium diisopropylamine,
Reacting with (CH ₃ ) ₂ CHCOOC ₂ H ₅ gives the structural formula: (Me represents a methyl group and Et represents an ethyl group.) A compound represented by the formula is obtained, treated with an acid, reacted with t-butyldiphenylsilyl chloride, and then cyclized to give the structural formula: (φ represents a phenyl group, ^tBu represents a t-butyl group, and Me is the same as above.) A compound represented by the following formula was obtained, and this compound was reacted with ethyl vinyl ether in the presence of an acid catalyst to obtain the structural formula: : (EE indicates ethoxyethyl group, φ, Me, ^t
Bu is the same as above. ) was obtained, and the compound was treated with CH ₃ COO (t-C ₄ H ₉ ) in the presence of lithium diisopropylamine.
Structural formula: (φ, Me, ^t Bu, EE are the same as above.) A compound represented by the following was obtained, and this compound was reacted with methyl orthoformate in the presence of camphorsulfonic acid to form the structural formula: (φ, Me, and ^t Bu are the same as above.) A compound represented by the following was obtained, and this compound was reacted with ethanedithiol in the presence of a Lewis acid to form the structural formula: (Me is the same as above) A compound represented by is obtained, and the compound is methylated to have the structural formula: (Me is the same as above) A compound represented by is obtained, and the compound is reduced to give the structural formula: (Me is the same as above.) _A compound _represented by the formula: (Me is the same as above) A compound represented by is obtained, and the compound is dethioacetalized to give the structural formula: (Me is the same as above) A compound represented by is obtained, and the compound is reduced,
Structural formula: (Me is the same as above) A compound represented by is obtained, and the compound is benzoylated to have the structural formula: (Me and φ are the same as above.) After demethoxymethylating the compound and acetylating it, the structural formula: (Me and φ are the same as above, and Ac represents an acetyl group.) A compound represented by the formula is obtained, and the compound is nitrified to have the structural formula: (Me and φ are the same as above.) A compound represented by the formula is obtained, and the compound is hydrolyzed to have the structural formula: (Me and φ are the same as above) A method for synthesizing an optically active (+)-pedamide, which is characterized by obtaining a compound represented by the following.