Process for the preparation of oxazoline compound

The present invention relates to a process for the preparation of an oxazoline compound which is easily chemically converted to a beta-amino-alpha-hydroxy acid or a gamma-amino-beta-hydroxy acid. The method comprises producing a compound of the following formula (4) using .alpha.-amino acid. The produced compound (4) is subjected to an intramolecular cyclization to produce an oxazoline compound of the following formula (3). The oxazoline compound (3) is oxidized at a vinyl group with RuCl.sub.3 or NaIO.sub.4 to produce an oxazoline compound of the following formula (1) which is easily chemically converted to a beta-amino-alpha-hydroxy acid. Alternatively, the oxazoline compound (3) may also be treated with 9-borabiclo[3.3.1]nonane such that a hydroxy group is introduced into the end of the vinyl group of the oxazoline compound(3). The introduced end hydroxy group is oxidized with RuCl.sub.3 or NaIO.sub.4 to produce an oxazoline compound of the following formula (2) which is easily chemically converted to a gamma-amino-hydroxy acid.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
The present invention relates to a process for the preparation of an 
oxazoline compound which is easily chemically converted to 
.gamma.-amino-.alpha.-hydroxy acid (hereinafter, called 
".beta.-a-.alpha.-h") or .gamma.-amino-.beta.-hydroxy acid (hereinafter, 
called ".gamma.-a-.beta.-h") exhibiting a strong pharmacological activity. 
2. Description of the Prior Art 
.beta.-a-.alpha.-h and .gamma.-a-.beta.-h are of great interest as very 
useful compounds because of having a variety of pharmacological activity. 
Examples of these compounds include (2R, 3S)-N-benzoyl-3-phenylisoserine 
of the following formula I which is a side chain of Taxol useful as an 
anti-cancer agent, (2S,3S)-3-amino-2-hydroxy-4-phenylbutanoic acid of the 
following formula II which is a non-leucine moiety of bestatine exhibiting 
immuno-modulating, anti-cancer and anti-fungal actions, and statin of the 
following formula III which is ACE (an Angiotensin Converting Enzyme) 
inhibitor, and 4-amino-3-hydroxy-5-phenylpentanoic acid which is an 
analogue of statin represented by the following formula IV. 
##STR1## 
There were disclosed many processes for the preparation of 
.beta.-a-.alpha.-h and .gamma.-a-.beta.-h. The preparation of 
(2R,3S)-N-benzoyl-3-phenylisoserine, which is a side chain of Taxol, was 
described in Tetrahedron Letters., 1994, 35, 2845-2848, 1994, 35, 
9289-9292, J. Org. Chem., 1994, 59, 1238-1240, and J. Am. Chem. Soc., 
1995, 117, 7824-7825. Moreover, David et al., in Tetrahedron Letters, 
1994, 26, 4483-4484, has reported the preparation of an oxazoline compound 
which was easily chemically converted to 
(2R,3S)-N-benzoyl-3-phenylisoserine. 
Furthermore, the preparation of (2S,3S)-3-amino-2-hydroxy-4-phenylbutanoic 
acid, which is a non-leucine moiety of bestatine, was disclosed in 
Tetrahedron Letters, 1995, 36, 909-912; Tetrahedron Letters, 1994, 35, 
6123-6126; and Tetrahedron Letters, 1993, 34, 7557-7560. 
Additionally, the preparations of statine represented by the above formula 
III, and of 4-amino-3-hydroxy-5-phenylpentanoic acid represented by the 
above formula IV, were described in J. Org. Chem., 1997, 62, 2292-2297; J. 
Org. Chem., 1995, 60, 6248-6249; U.S. Pat. No. 4,803,292; and Tetrahedron 
Letters, 190, 31, 7359-7362. 
SUMMARY OF THE INVENTION 
The present invention provides a process for the preparation of an 
oxazoline compound capable of being easily chemically converted to 
.beta.-a-.alpha.-h or .gamma.-a-.beta.-h having a strong pharmacological 
activity. For the starting material in this process, an .alpha.-amino acid 
is used, such as alanine, valine, leucine, cystein, cyclohexylglycine, 
cyclohexylalanine, phenylglycine, p-hydroxyphenylglycine, phenylalanine, 
or p-hydroxyphenylalanine. Moreover, after the starting material is 
subjected to several reaction steps, the resulting compound is subjected 
to an intramolecular cyclization reaction while using a palladium compound 
as a catalyst to produce the oxazoline compound. 
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
The foregoing and other objects, features and advantages of the invention 
will be apparent to those skilled in the art to which the present 
invention relates from reading the following specification. 
In accordance with the present invention, an .alpha.-amino acid, such as 
alanine, valine, leucine, cystein, cyclohexylglycine, cyclohexylalanine, 
phenylglycine, p-hydroxyphenylglycine, phenylalanine, or 
p-hydroxyphenylalanine, is used as the starting material to produce a 
compound represented by the following formula (4). 
##STR2## 
Thereafter, the compound of the formula (4) is subjected to an 
intramolecular cyclization reaction while using a palladium compound as a 
catalyst to produce an oxazoline compound represented by the following 
formula (3). 
##STR3## 
The produced oxazoline compound of the formula (3) is then oxidized at a 
vinyl group with RuCl.sub.3 and NaIO.sub.4 so as to produce an oxazoline 
compound of the following formula (1) which is easily chemically converted 
ot a beta-amino-alpha-hydroxy acid. 
##STR4## 
Alternatively, the produced oxazoline compound of the formula (3) is 
treated with 9-borabicyclo[3.3.1]nonane such that a hydroxy group is 
introduced into the end of a vinyl group of the oxazoline compound (3). 
The introduced end hydroxy end group is then oxidized with RuCl.sub.3 and 
NaIO.sub.4 so as to produce an oxazoline compound of the following formula 
(2) which is easily chemically converted into a gamma-amino-alpha-hydroxy 
acid. 
##STR5## 
The process of the present invention is composed of the preparation of a 
compound of the formula (4) capable of reacting with palladium using 
.alpha.-amino acid as the starting material, and the preparation of the 
oxazoline compound of the formula (1) or (2) by an intramolecular 
cyclization reaction of the compound (4) using a palladium compound as a 
catalyst. 
The preparation of a compound of the formula (4) capable of reacting with 
palladium is carried out as indicated in the following reaction scheme I: 
##STR6## 
where R is methyl, isopropyl, isobutyl, sec-butyl, thiomethyl, cyclohexyl, 
cyclohexylmethyl, phenyl, p-hydroxyphenyl, phenylmethyl, or 
p-hydroxyphenylmethyl, LAH is lithium aluminum hydride (Li(AlH.sub.4)), 
THF is tetrahydrofuran, DMSO is dimethylsulfoxide, DMAP is 
dimethylaminopyridine, DIBAL is diisobutylaluminum hydride, Bz is benzoyl, 
and X is acetate, benzoate, or carbonate, or halide such as Cl, Br, or I. 
The preparation of the oxazoline compound of the formula (4) will be 
described with reference to the reaction scheme I. 
For the preparation of the compound of the formula (4), 2.0 to 3.0 
equivalents of .alpha.-amino acid are stirred at a temperature of 60 to 
100.degree. C. for 6 to 10 hours to give amino alcohol to which 1.0 to 1.5 
equivalents of di-tert-butyl bicarbonate is then added. The resulting 
mixture is stirred at a temperature of 40 to 60.degree. C. for 6 to 10 
hours to obtain N-tert-butyloxycarbonyl amino alcohol. 
Then, the obtained N-tert-butyloxycarbonyl amino alcohol is reacted with 
1.0 to 2.0 equivalents of oxalyl chloride, 1.1 to 2.1 equivalents of 
dimethylsulfoxide, and 4.0 to 8.0 equivalents of diisopropylethylamine at 
a temperature of -78.degree. C. for one hour to obtain aldehyde. Next, the 
obtained aldehyde is reacted with 1.0 to 1.5 equivalents of lithium 
chloride, 1.0 to 1.5 equivalents of trimethylphosphonoacetate, and 1.0 to 
1.5 equivalents of diisopropylethylamine for 1 to 24 hours in the presence 
of an anhydrous acetonitrile solvent to produce .alpha.,.beta.-unsaturated 
ester. 
Following this, the produced a, -unsaturated ester is reacted with 1.0 to 
1.5 equivalents of boron trifluoride-diethyl etherate and 3.0 to 4.0 
equivalents of diisobutylaluminium at a temperature of -60 to -78.degree. 
C. for 30 minutes to 2 hours to produce allyl alcohol. 
Then, the produced allyl alcohol is reacted with a solution of 2N to 4N HCl 
in ethyl acetate at room temperature for 1 to 3 hours, followed by 
reacting with 0.95 to 1.05 equivalents of benzoyl chloride, to produce 
N-benzoyl allyl alcohol. Further, allyl alcohol in the produced N-benzoyl 
allyl alcohol is converted to a leaving group indicated by the symbol X in 
the reaction scheme I. 
As the leaving agent, acetate, benzoate, carbonate, or halide is used. The 
acetate, benzoate, or carbonate is prepared with 1.0 to 1.2 equivalents of 
acetic anhydride, benzoyl chloride, or methyl chloroformate, respectively. 
The halide is prepared with 1.0 to 2.0 equivalents of methane sulfonyl 
halide, 0.1 to 0.5 equivalents of dimethylaminopyridine, and 1.0 to 2.0 
equivalents of triethylamine. 
The preparation of the oxazoline compound of the formula (1) or (2) is 
carried out as indicated in the following reaction scheme II: 
##STR7## 
where R is methyl, isopropyl, isobutyl, sec-butyl, thiomethyl, cyclohexyl, 
cyclohexylmethyl, phenyl, p-hydroxyphenyl, phenylmethyl, or 
p-hydroxyphenylmethyl, 9-BBN is 9-borabicyclo[3.3.1]nonane, THF is 
tetrahydrofuran, Pd(Ph.sub.3).sub.4 is tetrakistriphenylphosphine 
palladium, and X is acetate, benzoate, or carbonate, or halide such as Cl, 
Br, or I. 
The preparation of the oxazoline compound of the formula (1) or (2) will be 
described with reference to the reaction scheme II. 
A base useful for the preparation of the oxazoline compound of the formula 
(3) from the compound of the formula (4) is 1.0 to 2.0 equivalents of 
sodium hydride, or 2.0 to 3.0 equivalents of calcium carbonate. If sodium 
hydride is used as the base, the compound of the formula (4) is then 
stirred in methylene chloride as a solvent at a temperature of 30 to 
40.degree. C. for 24 to 48 hours to obtain the compound of the formula 
(3). On the other hand, if calcium hydride is used as a base, the compound 
of the formula (4) is then stirred in acetonitrile as a solvent at a 
temperature of 80 to 120.degree. C. for 2 to 12 hours to obtain the 
compound of the formula (3). 
For the preparation of the compound of the formula (2) from the compound of 
the formula (3), the compound of the formula (3) is stirred together with 
0.02 to 0.2 equivalents of ruthenium chloride, 4.5 to 8.5 equivalents of 
sodium bicarbonate, and 4.5 to 6.5 equivalents of sodium periodate at room 
temperature for 24 to 72 hours. A solvent used in the stirring is a mixed 
solvent of acetonitrile/carbon tetrachloride/water=1:1:1 to 2:2:3 (v/v), 
and used in the amount of 1 to 20 ml relative to one mmol of the compound 
of the formula (3). 
Meanwhile, the preparation of the compound of the formula (1) from the 
compound of the formula (3) is composed of a hydroboration and then an 
oxidation. For the hydroboration, after the compound of the formula (3) is 
reacted with 2 to 6 equivalents of 9-BBN at room temperature for 12 to 36 
hours, the resulting compound is treated with ethyl alcohol, 6N NaOH, or 
H.sub.2 O.sub.2 to obtain a primary alcohol. The obtained alcohol is then 
oxidized to produce the compound of the formula (1) For the oxidation, the 
obtained alcohol is stirred together with 0.02 to 0.16 equivalents of 
ruthenium chloride, 4.5 to 8.5 equivalents of sodium bicarbonate, and 4.5 
to 6.5 equivalents of sodium periodate at room temperature for 12 to 24 
hours. A solvent used in the stirring is a mixed solvent of 
acetonitrile/carbon tetrachloride/water=1:1:1 to 2:2:3 (v/v), and used in 
the amount of 1 to 20 ml relative to one mmol of the compound of the 
formula (3). 
Even though the palladium compound used as a catalyst in the present 
invention is indicated above to be tetrakistriphenylphosphine palladium, 
it is also possible to use a compound having, as a ligand, 
tributylphosphine palladium, tri-o-tolylphosphine palladium, 
tri-p-tolylphosphine palladium, or tris(dibenzylidene)dipalladium. 
Moreover, although a mixture of palladium acetate (Pd(OAc.sub.2) or 
palladium chloride (PdCl.sub.2) with triphenylphosphine (Ph.sub.3 P) may 
also used as a catalyst while resulting in an excellent reactivity, it is 
most preferable to use tetrakistriphenylphosphine palladium as a catalyst. 
The present invention will be further described with reference to the 
following examples. Note, however, that the examples are included herein 
for only explanation purpose and they are not restrictive of the present 
invention.

EXAMPLE 1 
Synthesis of N-tert-butyloxy-carbonylphenylglycinol 
4.55 g (120 mmol) of lithium aluminum hydride (Li(AlH.sub.4) was suspended 
in 210 ml of tetrahydrofuran to which 9.07 g (60 mmol) of 
(S)-(+)-phenylglycine was then slowly added. After adding 
(S)-(+)-phenylglycine, the mixture was heated to reflux at 90.degree. C. 
for 6 hours, cooled to room temperature, added with 7.3 ml of 10% aqueous 
sodium hydroxide solution and 9.1 ml of H.sub.2 O in sequence, and then 
stirred for 5 minutes. 
At the end of the stirring, a solution of 14.40 g (66 mmol) of 
di-tert-butyl bicarbonate and 200 mg (1.64 mmol) of dimethyl aminopyridine 
in 80 ml of methylene chloride was added. The mixture was heated to reflux 
at 90.degree. C. for 6 hours, cooled to room temperature, filtered through 
a sodium sulfate (Na.sub.2 SO.sub.4) pad, and then washed with methylene 
chloride four times. 
Following the washing, an organic layer was concentrated under reduced 
pressure, and then recrystallized from cyclohexane, thereby obtaining 
10.49 g (74% yield) of N-tert-butyloxy-carbonylphenylglycinol. 
.sup.1 H N(CDCl.sub.3) .delta. 1.43(s, 9H), 3.82(br s, 2H), 4.77(br s, 1H), 
5.31(br s, 1H), 7.26-7.38(m, 5H); 
.sup.13 C NMR (CDCL.sub.3) .delta. 22.1, 57.6, 67.6, 80.7, 127.3, 128.4, 
129.5, 140.1, 156.8 
EXAMPLE 2 
Synthesis of N-tert-butyloxycarbonylphenylalaninol 
4.55 g (120 mmol) of lithium aluminum hydride (Li(AlH.sub.4) was suspended 
in 210 ml of tetrahydrofuran to which 9.91 g (60 mmol) of 
(S)-(+)-phenylalanine was then carefully added. After adding 
(S)-(+)-phenylalanine, the mixture was heated to reflux at 90.degree. C. 
for 6 hours, cooled to room temperature, added with 7.3 ml of 10% aqueous 
sodium hydroxide solution and 9.1 ml of H.sub.2 O in sequence, and then 
stirred for 5 minutes. 
At the end of the stirring, a solution of 14.40 g (66 mmol) of 
di-tert-butyl bicarbonate and 200 mg (1.64 mmol) of dimethyl aminopyridine 
in 80 ml of methylene chloride was added. The mixture was heated to reflux 
at 70.degree. C. for 6 hours, cooled to room temperature, filtered through 
a sodium sulfate (Na.sub.2 SO.sub.4) pad, and then washed with methylene 
chloride four times. 
Following the washing, an organic layer was concentrated under reduced 
pressure, and then recrystallized from methylene chloride-cyclohexane, 
thereby obtaining 11.31 g (75% yield) of 
N-tert-butyloxy-carbonylphenylalaninol. 
.sup.1 H NMR (CDCl.sub.3) .delta. 1.39(s, 9H), 2.85(d, J=7.2 Hz, 2H), 
3.56(dd, J=10.8 Hz, J=5.4 Hz, 1H), 3.67 (dd, J=10.8 Hz, J=3.6 Hz, 1H), 
3.88(m, 1H), 4.86(br s, 1H), 7.22-7.34(m, 5H); 
.sup.13 C NMR (CDCL.sub.3) .delta. 28.3, 37.5, 53.7, 64.2, 79.7, 126.5, 
128.5, 129.3, 137.8, 156.1 
EXAMPLE 3 
Synthesis of N-tert-butylcarbonylleucinol 
4.55 g (120 mmol) of lithium aluminum hydride (Li(AlH.sub.4) was suspended 
in 210 ml of tetrahydrofuran to which 7.87 g (60 mmol) of (S)-(+)-leucine 
was then carefully added. After adding (S)-(+)-leucine, the mixture was 
heated to reflux at 90.degree. C. for 6 hours, cooled to room temperature, 
added with 7.3 ml of 10% aqueous sodium hydride solution and 9.1 ml of 
H.sub.2 O in sequence, and then stirred for 5 minutes. 
At the end of the stirring, a solution of 14.40 g (66 mmol) of 
di-tert-butyl bicarbonate and 200 mg (1.64 mmol) of dimethyl aminopyridine 
in 80 ml of methylene chloride was added. The mixture was heated to reflux 
at 70.degree. C. for 6 hours, cooled to room temperature, filtered through 
a sodium sulfate (Na.sub.2 SO.sub.4) pad, and then washed with methylene 
chloride four times. 
Following the washing, an organic layer was concentrated under reduced 
pressure, and then purified by column chromatography (hexane:ethyl 
acetate=3:1), thereby obtaining 8.74 g (67% yield) of 
N-tert-butyloxy-carbonylphenylglycinol. 
.sup.1 H NMR (CDCl.sub.3) .delta. 0.39(dd, 6H), 1.31(m, 2H), 1.45(s, 9H), 
1.664(m, 1H), 2.56(br s, 1H), 3.50(dd, J=10.5 Hz, J=6.0 Hz, 1H), .delta. 
3.66(d, J=10.5 Hz, 1H), 3.72(m, 1H), 4.58(br s, 1H); 
.sup.13 C NMR (CDCL.sub.3) .delta. 22.9, 23.7, 25.5, 29.1, 41.3, 51.7, 
67.2, 80.3, 157.2 
EXAMPLE 4 
Synthesis of 2-N-(tert-butyloxycarbonyl)-amino-3-cyclohexyl-1-propanol 
2 g (10.3 mmol) of (S)-2-amino-3-cyclohexyl-1-propanol, 2.26 g (10.3 mmol) 
of sodium hydrogen carbonate (NaHCO.sub.3), and 2.6 g (31 mmol) of 
di-tert-butyl bicarbonate were suspended in 50 ml of methanol. The mixture 
was stirred at room temperature for 8 hours. 
At the end of the reaction, the product was filtered, concentrated under 
reduced pressure to remove methanol, a solvent. Next, the concentrate was 
diluted with 30 ml of diethyl ether, and then further filtered. Following 
the 20 filtration, an organic layer was concentrated under reduced 
pressure, and then purified by column chromatography (hexane:ethyl 
acetate=1:1), thereby obtaining 2.42 g (91% yield) of 
2-N-(tert-butyloxycarbonyl)-amino-3-cyclohexyl-1-propanol. 
.sup.1 H NMR (CDCl.sub.3) .delta. 0.84-0.96(m, 2H), 1.12-1.28(m, 8H), 
1.64(s, 9H), 1.75(m, 2H), 1.78(d, 1H), 3.49(dd, J=10.5 Hz, J=6.5 Hz, 1H), 
3.66(d, J=10.5 Hz, 1H), 3.74(m, 1H), 4.57(br s, 1H); 
.sup.13 C NMR (CDCL.sub.3) .delta. 26.8, 27.0, 27.2, 29.0, 33.6, 34.4, 
34.9, 39.8, 51.0, 67.4, 80.3, 157.3 
EXAMPLE 5 
Synthesis of methyl 4-(N-tert-butyloxycarbonyl)-amino-4-phenyl-2-butenoate 
1.05 ml (12.0 mmol) of oxalyl chloride was added to 20 ml of methylene 
chloride. The mixture is cooled to a temperature of -78.degree. C., and 
then added with 0.91 ml (12.8 mmol) of dimethylsulfoxide. Next, after the 
resulting mixture was stirred at -78.degree. C. for 5 minutes, the 
reaction temperature was elevated to -60.degree. C., and a suspension of 
1.88 g (7.8 mmol) of N-tert-butyloxycarbonyphenylglycinol in 25 ml of 
methylene chloride-dimethylsulfoxide (24:1) was then added. 
After the reaction temperature was elevated to -35.degree. C., the mixture 
was stirred for 10 minutes, added dropwise with 8.36 ml (48.0 mmol) of 
diisopropylethylamine for 5 minutes, and then further stirred for 10 
minutes. After the reaction temperature was elevated to room temperature, 
40 ml of H.sub.2 O was added. Next, an organic layer was isolated, washed 
with 20 ml of 1N HCl, and then with 20 ml of brine, dried with magnesium 
sulfate (MgSO.sub.4), filtered, concentrated under reduced pressure, and 
then used in the subsequent reaction without purification. 
397 mg (9.4 mmol) of lithium chloride was suspended in 100 ml of anhydrous 
acetonitrile. To this suspension, 1.5 ml (9.4 mmol) of 
trimethylphosphonoacetate, 1.36 ml (7.8 mmol) of diisopropylethylamine, 
and aldehyde prepared as described above, were sequentially added, and 
then stirred for 24 hours. 
At the end of the stirring, the resulting material was added with 100 ml of 
H.sub.2 O, extracted with 50 ml of ethyl acetate twice, washed with 50 ml 
of 1H HCl twice, and then with 50 ml of brine twice, dried with 
MgSO.sub.4, filtered, and then concentrated under reduced pressure. The 
concentrate was recrystallized from diethyl ether-petroleum ether, thereby 
obtaining 1.83 g (83%) of methyl 
4-(N-tert-butyloxycarbonyl)-amino-4-phenyl-2-butenoate. 
.sup.1 H NMR (CDCl.sub.3) .delta. 1.44(s, 9H), 3.75(s, 3H), 4.97(br s, 1H), 
5.44(br s, 1H), 5.99(dd, J=15.5 Hz, J=1.5 Hz, 1H), 7.07(dd, J=15.5 Hz, 
J=5.0 Hz, 1H), 7.25-7.37(m, 5H); 
.sup.13 C NMR (CDCL.sub.3) .delta. 29.0, 52.4, 56.2, 80.9, 121.8, 127.9, 
128.9, 129.7, 139.9, 148.1, 155.5, 167.3 
EXAMPLE 6 
Synthesis of methyl 4-(N-tert-butyloxycarbonyl)amino-5-phenyl-2-pentenoate 
1.05 ml (12.0 mmol) of oxalyl chloride was added to 20 ml of methylene 
chloride. The mixture is cooled to a temperature of -78.degree. C., and 
then added with 0.91 ml (12.8 mmol) of dimethylsulfoxide. Next, after the 
resulting mixture was stirred at -78.degree. C. for 5 minutes, the 
reaction temperature was elevated to -60.degree. C., and a suspension of 
1.96 g (7.8 mmol) of N-tert-butyloxycarbonyphenylalaniol in 25 ml of 
methylene chloride-dimethylsulfoxide (24:1) was then added. 
After the reaction temperature was elevated to -35.degree. C., the mixture 
was stirred for 10 minutes, added dropwise with 8.36 ml (48.0 mmol) of 
diisopropylethylamine for 5 minutes, and then further stirred for 10 
minutes. After the reaction temperature was elevated to room temperature, 
40 ml of H.sub.2 O was added. Next, an organic layer was isolated, washed 
with 20 ml of 1N HCl, and then with 20 ml of brine, dried with magnesium 
sulfate (MgSO.sub.4), filtered, concentrated under reduced pressure, and 
then used in the subsequent reaction without purification. 
397 mg (9.4 mmol) of lithium chloride was suspended in 100 ml of anhydrous 
acetonitrile. To this suspension, 1.5 ml (9.4 mmol) of 
trimethylphosphonoacetate, 1.36 ml (7.8 mmol) of diisopropylethylamine, 
and aldehyde prepared as described above, were sequentially added, and 
then stirred for 24 hours. 
At the end of the stirring, the resulting material was added with 100 ml of 
H.sub.2 O, extracted with 50 ml of ethyl acetate twice, washed with 50 ml 
of 1H HCl twice, and then with 50 ml of brine twice, dried with 
MgSO.sub.4, filtered, and then concentrated under reduced pressure. The 
concentrate was recrystallized from diethyl ether-petroleum ether, thereby 
obtaining 2.07 g (87% yield) of methyl 
4-(N-tert-butyloxycarbonyl)amino-5-phenyl-2-pentenoate. 
.sup.1 H NMR (CDCl.sub.3) .delta. 1.40(s, 9H), 2.89(d, J=6.3 Hz, 2H), 
3.72(s, 3H), 4.56(m, 2H), 5.86(dd, J=15.6 Hz, J=1.5 Hz, 1H), 6.91(dd, 
J=15.6 Hz, J=5.1 Hz, 1H), 7.16-7.33(m, 5H); 
.sup.13 C NMR (CDCL.sub.3) .delta. 28.3, 40.8, 51.6, 53.7, 80.0, 120.7, 
126.9, 128.6, 129.4, 136.3, 147.9, 154.9, 166.6 
EXAMPLE 7 
Synthesis of methyl 4-(N-tert-butyloxycarbonyl)-amino-6-methyl-2-heptenoate 
1.05 ml (12.0 mmol) of oxalyl chloride was added to 20 ml of methylene 
chloride. The mixture is cooled to a temperature of -78.degree. C., and 
then added with 0.91 ml (12.8 mmol) of dimethylsulfoxide. Next, after the 
resulting mixture was stirred at -78.degree. C. for 5 minutes, the 
reaction temperature was elevated to -60.degree. C., and a suspension of 
1.70 g (7.8 mmol) of N-tert-butyloxycarbony-leucinol in 25 ml of methylene 
chloride-dimethylsulfoxide (24:1) was then added. 
After the reaction temperature was elevated to -35.degree. C., the mixture 
was stirred for 10 minutes, added dropwise with 8.36 ml (48.0 mmol) of 
diisopropylethylamine for 5 minutes, and then further stirred for 10 
minutes. After the reaction temperature was elevated to room temperature, 
40 ml of H.sub.2 O was added. Next, an organic layer was isolated, washed 
with 20 ml of 1N HCl, and then with 20 ml of brine, dried with magnesium 
sulfate (MgSO.sub.4), filtered, concentrated under reduced pressure, and 
then used in the subsequent reaction without purification. 
397 mg (9.4 mmol) of lithium chloride was suspended in 100 ml of anhydrous 
acetonitrile. To this suspension, 1.5 ml (9.4 mmol) of 
trimethlylphosphonoacetate, 1.36 ml (7.8 mmol) of diisopropylethylamine, 
and aldehyde prepared as described above, were sequentially added, and 
then stirred for 24 hours. 
At the end of the stirring, the resulting material was added with 100 ml of 
H.sub.2 O, extracted with 50 ml of ethyl acetate twice, washed with 50 ml 
of 1H HCl twice, and then with 50 ml of brine twice, dried with 
MgSO.sub.4, filtered, and then concentrated under reduced pressure. The 
concentrate was purified by column chromatography (hexane:ethyl 
acetate=8:1), thereby obtaining 1.52 g (72% yield) of methyl 
4-(N-tert-butyloxycarbonyl)-amino-6-methyl-2-heptenoate. 
.sup.1 H NMR (CDCl.sub.3) .delta. 0.94(dd, 6H), 1.38(m, 2H), 1.45(s, 9H), 
1.69(m, 1H), 3.73(s, 3H), 4.33(m, 1H), 4.45(br s, 1H), 5.92(dd, J=15.8 Hz, 
J=1.5 Hz, 1H), 6.84(dd, J=15.5 Hz, J=5.5 Hz, 1H); 
.sup.13 C NMR (CDCL.sub.3) .delta. 22.2, 22.7, 24.7, 28.3, 43.8, 49.8, 
51.6, 80.3, 120.0, 149.2, 155.1, 166.8 
EXAMPLE 8 
Synthesis of methyl 
4-(N-tert-butyloxycarbonyl)-amino-5-cyclohexyl-2-pentenoate 
1.07 ml (12.0 mmol) of oxalyl chloride was added to 20 ml of methylene 
chloride. The mixture is cooled to a temperature of -78.degree. C., and 
then added with 4.17 ml (23.5 mmol) of dimethylsulfoxide. Next, after the 
resulting mixture was stirred at -78.degree. C. for 5 minutes, the 
reaction temperature was elevated to -60.degree. C., and a suspension of 
2.42 g (9.4 mmol) of 
N-tert-butyloxycarbony-2-amino-3-cyclohexyl-1-propanol in 25 ml of 
methylene chloride-dimethylsulfoxide (24:1) was then added dropwise in a 
state where the suspension was dissolved in 10 ml of methylene chloride. 
After the reaction temperature was elevated to -35.degree. C., the mixture 
was stirred for 10 minutes, added with 6.56 ml (47.0 mmol) of 
diisopropylethylamine for 5 minutes dropwise, and then further stirred for 
10 minutes. After the reaction temperature was elevated to room 
temperature, 16 ml of H.sub.2 O was added. Next, an organic layer was 
isolated, washed with 20 ml of 1N HCl, and then with 20 ml of brine, dried 
with magnesium sulfate (MgSO.sub.4), filtered, concentrated under reduced 
pressure, and then used in the subsequent reaction without purification. 
478 mg (11.2 mmol) of lithium chloride and 1.83 ml (11.2 mmol) of 
trimethylphosphonoacetate was suspended in 50 ml of anhydrous 
acetonitrile. To this suspension, 1.41 ml (9.4 mmol) of 
1,8-diazabicyclo[5,4,0]undec-7-ene and aldehyde prepared as described 
above and dissolved in 20 ml of acetonitrile, were sequentially added, and 
then stirred for 24 hours. 
At the end of the stirring, the resulting material was added with 20 ml of 
H.sub.2 O, extracted with 50 ml of ethyl acetate twice, washed with 20 ml 
of 1H HCl twice, and then with 50 ml of brine twice, dried with 
MgSO.sub.4, filtered, and then concentrated under reduced pressure. The 
concentrate was purified by column chromatography (hexane:ethyl 
acetate=8:1), thereby obtaining 2.04 g (70% yield) of methyl 
4-(N-tert-butyloxycarbonyl)-amino-5-cyclohexyl-2-pentenoate. 
.sup.1 H NMR (CDCl.sub.3) .delta. 0.90-0.96(m, 2H), 1.15-1.28(m, 8H), 
1.64(s, 9H), 1.71(m, 1H), 1.78(d, 1H), 3.74(s, 3H), 4.37(br s, 1H), 
4.43(br s, 1H), 5.92(dd, J=15.5 Hz, J=1.5 Hz, 1H), 6.84(dd, J=15.5 Hz, 
J=5.0 Hz, 1H); 
.sup.13 C NMR (CDCL.sub.3) .delta. 26.0, 26.1, 26.4, 28.3, 32.4, 32.9, 
33.4, 42.4, 51.5, 51.8, 77.4, 119.9, 149.3, 152.1, 166.8 
EXAMPLE 9 
Synthesis of 4-(N-tert-butyloxycarbonyl)amino-4-phenyl-2-butene-1-ol 
29.1 g (100 mmol) of methyl 
4-(N-tert-butyloxycarbonyl)amino-4-phenyl-2-butenoate was added to 200 ml 
of methylene chloride. The mixture is cooled to a temperature of 
-78.degree. C., and then added with 13.5 ml (100 mmol) of boron 
trifluoride-diethyl etherate dropwise. Next, the resulting mixture was 
stirred at -78.degree. C. for 30 minutes, then added with a solution of 
200 ml (300 mmol) of diisobutylaluminum hydride in 1.5 mol of toluene. 
After stirring for 1 hour, the stirred mixture was added with a solution 
of 5M acetic acid in 230 ml of methylene chloride dropwise. Then, the 
reaction temperature was elevated to room temperature, and 500 ml of an 
aqueous solution of 3M tartaric acid was added. Following this, an organic 
layer was isolated, a water layer was washed with 200 ml of methylene 
chloride, and then combined with the organic layer. Then, the resulting 
organic layer was washed with 500 ml of a saturated aqueous solution of 
sodium bicarbonate, and then with 500 ml of brine, dried with magnesium 
sulfate (MgSO.sub.4), filtered, and concentrated under reduced pressure. 
The concentrate was recrystallized from ether-petroleum ether, thereby 
obtaining 23.4 g (89% yield) of 
4-(N-tert-butyloxycarbonyl)-amino-4-phenyl-2-butene-1-ol. 
.sup.1 H NMR (CDCl.sub.3) .delta. 1.44(s, 9H), 4.19(dd, J=5.0 H, J=1.0 Hz, 
2H), 4.90(br s, 1H), 5.30(br s, 1H), 5.81(dt, J=15.5 Hz, J=5.0 Hz, 1H), 
5.88(dd, J=15.5 Hz, J=5.5 Hz, 1H), 7.23-7.36(m, 5H); 
.sup.13 C NMR (CDCL.sub.3) .delta. 29.1, 56.5, 63.6, 80.5, 127.6, 128.3, 
129.4, 131.1, 132.0, 142.0, 155.7 
EXAMPLE 10 
Synthesis of 4-(N-tert-butyloxycarbonyl)amino-5-phenyl-2-pentene-1-ol 
30.5 g (100 mmol) of methyl 
4-(N-tert-butyloxycarbonyl)amino-5-phenyl-2-pentenoate was added to 200 ml 
of methylene chloride. The mixture is cooled to a temperature of 
-78.degree. C., and then added with 13.5 ml (100 mmol) of boron 
trifluoride-diethyl etherate dropwise. Next, the resulting mixture was 
stirred at -78.degree. C. for 30 minutes, then added with a solution of 
200 ml (300 mmol) of diisobutylaluminum hydride in 1.5 mol of toluene. 
After stirring for 1 hour, the stirred mixture was added with a solution 
of 5M acetic acid in 230 ml of methylene chloride dropwise. Then, the 
reaction temperature was elevated to room temperature, and 500 ml of an 
aqueous solution of 3M tartaric acid was added. Following this, an organic 
layer was isolated, a water layer was washed with 200 ml of methylene 
chloride, and then combined with the organic layer. Then, the resulting 
organic layer was washed with 500 ml of a saturated aqueous solution of 
sodium bicarbonate, and then with 500 ml of brine, dried with magnesium 
sulfate (MgSO.sub.4), filtered, and concentrated under reduced pressure. 
The concentrate was recrystallized from ether-petroleum ether, thereby 
obtaining 25.5 g (92% yield) of 
4-(N-tert-butyloxycarbonyl)-amino-5-phenyl-2-pentene-1-ol. 
.sup.1 H NMR (CDCl.sub.3) .delta. 1.39(s, 9H), 2.83(d, J=6.9 Hz, 2H), 
4.09(br s, 1H), 4.41(br s, 1H), 4.54(br s, 1H),5.69(m, 2H), 7.16-7.32(m, 
5H); 
.sup.13 C NMR (CDCL.sub.3) .delta. 28.3, 41.6, 56.0, 62.7, 79.5, 126.4, 
128.3, 129.5 129.7, 131.4, 137.3, 155.2 
EXAMPLE 11 
Synthesis of 4-(N-tert-butyloxycarbonyl)amino-6-methyl-2-heptene-1-ol 
27.1 g (100 mmol) of methyl 
4-(N-tert-butyloxycarbonyl)amino-6-methyl-2-heptenoate was added to 200 ml 
of methylene chloride. The mixture is cooled to a temperature of 
-78.degree. C., and then added with 13.5 ml (100 mmol) of boron 
trifluoride-diethyl etherate dropwise. Next, the resulting mixture was 
stirred at -78.degree. C. for 30 minutes, then added with a solution of 
200 ml (300 mmol) of diisobutylaluminum hydride in 1.5 mol of toluene 
dropwise. After stirring for 1 hour, the stirred mixture was added with a 
solution of 5M acetic acid in 230 ml of methylene chloride dropwise. Then, 
the solution was elevated to room temperature, and 500 ml of an aqueous 
solution of 3M tartaric acid was added. Following this, an organic layer 
was isolated, a water layer was washed with 200 ml of methylene chloride, 
and then combined with the organic layer. Then, the resulting organic 
layer was washed with 500 ml of a saturated aqueous solution of sodium 
bicarbonate, and then with 500 ml of brine, dried with magnesium sulfate 
(MgSO.sub.4), filtered, and concentrated under reduced pressure. The 
concentrate was purified by column chromatography (hexane:ethyl 
acetate=2:1), thereby obtaining 20.4 g (84% yield) of 
4-(N-tert-butyloxycarbonyl)amino-6-methyl-2-heptene-1-ol. 
.sup.1 H NMR (CDCl.sub.3) .delta. 0.89(dd, 6H), 1.30(m, 2H), 1.41(s, 9H), 
1.61(m, 1H), 4.11(t, 3H), 4.38(br s, 1H), 5.55-5.60(m, 1H), 5.71-5.77(m, 
1H); 
.sup.13 C NMR (CDCL.sub.3) .delta. 22.4, 22.7, 24.7 28.4, 44.7, 50.1, 63.1, 
79.7 129.0, 133.0, 155.3 
EXAMPLE 12 
Synthesis of 4-(N-tert-butyloxycarbonyl)amino-5-cyclohexyl-2-pentene-1-ol 
2.04 g (6.5 mmol) of methyl 
4-(N-tert-butyloxycarbonyl)amino-5-cyclohexyl-2-pentenoate was added to 
200 ml of methylene chloride. The mixture is cooled to a temperature of 
-78.degree. C., and then added with 0.88 ml (7.1 mmol) of boron 
trifluoride-diethyl etherate dropwise. Next, the resulting mixture was 
stirred at -78.degree. C. for 30 minutes, then added with a solution of 
13.0 ml (19.5 mmol) of diisobutylaluminum hydride in 1.5 mol of toluene. 
After stirring for 1 hour, the stirred mixture was added with a solution 
of 5M acetic acid in 14 ml of methylene chloride dropwise. Then, the 
reaction temperature was elevated to room temperature, and 55 ml of an 
aqueous solution of 3M tartaric acid was added. Following this, an organic 
layer was isolated, a water layer was washed with 60 ml of methylene 
chloride, and then combined with the organic layer. Then, the resulting 
organic layer was washed with 50 ml of a saturated aqueous solution of 
sodium bicarbonate, and then with 50 ml of brine, dried with magnesium 
sulfate (MgSO.sub.4), filtered, and concentrated under reduced pressure. 
The concentrate was purified by column chromatography (hexane:ethyl 
acetate=2:1), thereby obtaining 1.59 g (86% yield) of 
4-(N-tert-butyloxycarbonyl)amino-5-cyclohexyl-2-pentene-1-ol. 
.sup.1 H NMR (CDCl.sub.3) .delta. 0.87(m, 2H), 1.14-1.31(m, 8H), 1.41(s, 
9H), 1.63(m, 2H), 1.71(d, 1H), 4.11(br s, 1H), 4.14(br s, 1H), 4.18(br s, 
1H), 5.59-5.61(m, 1H), 5.70-5.76(m, 1H); 
.sup.13 C NMR (CDCL.sub.3) .delta. 26.1, 26.2, 26.4, 28.4, 33.0, 33.4, 
34.1, 43.3, 49.2, 63.1, 77.4, 128.8, 133.1, 153.0 
EXAMPLE 13 
Synthesis of 4-(N-benzoyl)amino-4-phenyl-1-acetoxy-2-butene 
2.6 g (10 mmol) of 4-(N-tert-butyloxycarbonyl)amino-4-phenyl-2-butene-1-ol 
was added to a solution of 10 ml of 3N-HCl in ethyl acetate, and the 
mixture was stirred for 30 minutes. After adding 20 ml of H.sub.2 O, the 
mixture was extracted with 30 ml of ethyl acetate. Then, a water layer was 
basified with potassium carbonate, extracted with 20 ml of methylene 
chloride twice, dried with MgSO.sub.4, filtered, and concentrated under 
reduced pressure, thereby obtaining 1.17 g (72% yield) of 
4-amino-4-phenyl-2-butene-1-ol. Next, the product was added with 20 ml of 
methylene chloride, cooled to 0.degree. C., and then added with 0.83 ml 
(7.17 mmol) of benzoyl chloride and 1.0 ml (7.17 mmol) of triethyl amine. 
After stirring for 1 hour, the mixture was added with 0.68 ml (7.17 mmol) 
of acetic anhydride and 0.58 ml (7.58 ml) of pyridine, and then further 
stirred for 24 hours. After the stirred solution was added with 20 ml of 
H.sub.2 O, an organic layer was isolated, washed with 20 ml of 1N-HCl, 20 
ml of a saturated aqueous solution of sodium carbonate, and then with 20 
ml of brine, filtered, and then concentrated under reduced pressure. The 
concentrate was recrystallized from methylene chloride-hexane, thereby 
obtaining 2.17 g (98%) of 4-(N-benzoyl)amino-4-phenyl-1-acetoxy-2-butene. 
.sup.1 H NMR (CDCl.sub.3) .delta. 2.08(s, 3H), 4.63(dt, J=4.5 Hz, J=1.5 Hz, 
2H), 5.82 (dt, J=15.5 Hz, J=6.0 Hz, 2H)5.89(dd, J=8.0 Hz, J=5.5 Hz, 1H), 
6.06(dd, J=15.5 Hz, J=5.5 Hz, 1H) 6.37(d, J=8.0 Hz, 1H), 7.31-7.54(m, 8H), 
7.79-7.81(m, 2H); 
.sup.13 C NMR (CDCL.sub.3) .delta. 21.6, 55.2, 64.8, 126.8, 127.7, 127.9, 
128.6, 129.3, 129.6, 132.4, 134.1, 134.9, 141.0, 167.1, 171.4 
EXAMPLE 14 
Synthesis of 4-(N-benzoyl)amino-5-phenyl-1-acetoxy-2-pentene 
2.77 g (10 mmol) of 
4-(N-tert-butyloxycarbonyl)amino-5-phenyl-2-pentene-1-ol was added to a 
solution of 10 ml of 3N-HCl in ethyl acetate, and the mixture was stirred 
for 30 minutes. After adding 20 ml of H.sub.2 O, the mixture was extracted 
with 30 ml of ethyl acetate. Then, a water layer was basified with 
potassium carbonate, extracted with 20 ml of methylene chloride twice, 
dried with MgSO.sub.4, filtered, and concentrated under reduced pressure, 
thereby obtaining 1.35 g (76% yield) of 4-amino-5-phenyl-2-pentene-1-ol. 
Next, the product was added with 20 ml of methylene chloride, cooled to 
0.degree. C., and then added with 0.88 ml (7.62 mmol) of benzoyl chloride 
and 1.06 ml (7.62 mmol) of triethyl amine. After stirring for 1 hour, the 
mixture was added with 0.72 ml (7.62 mmol) of acetic anhydride and 0.62 ml 
(7.62 ml) of pyridine, and then further stirred for 24 hours. After the 
stirred solution was added with 20 ml of H.sub.2 O, an organic layer was 
isolated, washed with 20 ml of 1N-HCl, 20 ml of a saturated aqueous 
solution of sodium carbonate, and then with 20 ml of brine, filtered, and 
then concentrated under reduced pressure. The concentrate was 
recrystallized from methylene chloride-hexane, thereby obtaining 2.43 g 
(99%) of 4-(N-benzoyl)amino-5-phenyl-1-acetoxy-2-pentene. 
.sup.1 H NMR (CDCl.sub.3) .delta. 2.05(s, 3H), 3.01(dd, J=6.5 Hz, J=1.5 Hz, 
2H), 4.54(d, J=6.0 Hz, 2H), 5.02(m, 1H), 5.71(dd, J=15.5 Hz, J=1.5 Hz, 
1H), 5.84 (dd, J=15.5 Hz, J=5.5 Hz, 1H), 6.11(d, J=8.0 Hz, 1H), 
7.22-7.49(m, 8H), 7.68-7.69(m, 2H); 
.sup.13 C NMR (CDCL.sub.3) .delta. 20.9, 41.0 51.3, 64.1, 117.9, 125.1, 
126.8, 128.5, 128.6, 129.5, 131.5, 133.8, 134.4, 136.8, 166.7, 170.6 
EXAMPLE 15 
Synthesis of 4-(N-benzoyl)amino-6-methyl-1-acetoxy-2-heptene 
2.4 g (10 mmol) of 4-(N-tert-butyloxycarbonyl)amino-6-methyl-2-heptene-1-ol 
was added to a solution of 10 ml of 3N-HCl in ethyl acetate, and the 
mixture was stirred for 30 minutes. After adding 20 ml of H.sub.2 O, the 
mixture was extracted with 30 ml of ethyl acetate. Then, a water layer was 
basified with potassium carbonate, extracted with 20 ml of methylene 
chloride twice, dried with MgSO.sub.4, filtered, and concentrated under 
reduced pressure, thereby obtaining 1.07 g (75% yield) of 
4-amino-6-methyl-2-heptene-1-ol. Next, the product was added with 20 ml of 
methylene chloride, cooled to 0.degree. C., and then added with 0.83 ml 
(7.17 mmol) of benzoyl chloride and 1.0 ml (7.17 mmol) of triethyl amine. 
After stirring for 1 hour, the mixture was added with 0.68 ml (7.17 mmol) 
of acetic anhydride and 0.58 ml (7.17 ml) of pyridine, and then further 
stirred for 24 hours. After the stirred solution was added with 20 ml of 
H.sub.2 O, an organic layer was isolated, washed with 20 ml of 1N-HCl, 20 
ml of a saturated aqueous solution of sodium carbonate, and then 20 ml of 
brine, filtered, and then concentrated under reduced pressure. The 
concentrate was purified by column chromatography (hexane:ethyl 
acetate=2:1), thereby obtaining 2.11 g (98%) of 
4-(N-benzoyl)amino-6-methyl-1-acetoxy-2-heptene. 
.sup.1 H NMR (CDCl.sub.3) .delta. 0.97(dd, 6H), 1.50(m, 2H), 1.71(m, 1H), 
2.07(s, 3H), 4.56(d, J=3.5 Hz, 2H), 4.78(m, 1H), 5.78(m, 2H), 5.96(d, 
J=7.5 Hz, 1H), 7.43-7.53(m, 3H), 7.77-7.79(m, 2H); 
.sup.13 C NMR (CDCL.sub.3) .delta. 20.9, 22.3, 22.8, 24.9, 44.2, 48.9, 
64.3, 124.4, 126.8, 128.5, 131.5, 134.5, 135.2, 166.6, 170.6 
EXAMPLE 16 
Synthesis of 4-(N-benzoyl)amino-5-cyclohexyl-1-acetoxy-2-pentene 
1.5 g (5.3 mmol) of 
4-(N-tert-butyloxycarbonyl)amino-5-cyclohexyl-2-pentene-1-ol was added to 
a solution of 10 ml of 3N-HCl in ethyl acetate, and the mixture was 
stirred for 30 minutes. After adding 20 ml of H20, the mixture was 
extracted with 30 ml of ethyl acetate. Then, a water layer was basified 
with potassium carbonate, extracted with 20 ml of methylene chloride 
twice, dried with MgSO.sub.4, filtered, and concentrated under reduced 
pressure, thereby obtaining 0.75 g (78% yield) of 
4-amino-5-cyclohexyl-2-pentene-1-ol. Next, the product was added with 20 
ml of methylene chloride, cooled to 0.degree. C., and then added with 0.49 
ml (4.29 mmol) of benzoyl chloride and 0.60 ml (4.29 mmol) of triethyl 
amine. After stirring for 1 hour, the mixture was added with 0.52 ml (6.43 
mmol) of acetic anhydride and 0.81 ml (8.58 mmol) of pyridine, and then 
further stirred for 24 hours. After the stirred solution was added with 20 
ml of H.sub.2 O, an organic layer was isolated, washed with 20 ml of 
1N-HCl, 20 ml of a saturated aqueous solution of sodium carbonate, and 
then with 20 ml of brine, filtered, and then concentrated under reduced 
pressure. The concentrate was purified by column chromatography 
(hexane:ethyl acetate=3:1), thereby obtaining 1.20 g (90% yield) of 
4-(N-benzoyl)amino-5-cyclohexyl-1-acetoxy-2-pentene. 
.sup.1 H NMR (CDCl.sub.3) .delta. 0.87-1.02(m, 2H), 1.10-1.26(m, 4H), 
1.33-1.41(m, 1H), 1.51(m, 1H), 1.72(m, 2H), 1.83(d, 1H), 2.06(s, 3H), 
4.57(m, 2H), 4.80(m, 1H), 5.75(m, 2H), 5.98(m, 1H), 7.42(m, 1H), 7.51(m, 
1H), 7.77(m, 1H); 
.sup.13 C NMR (CDCL.sub.3) .delta. 21.7, 26.8, 26.9, 27.1, 33.6, 34.2, 
35.0, 43.5, 48.9, 65.0, 124.9, 127.5, 129.3, 132.2, 135.2, 136.1, 167.3, 
171.4 
EXAMPLE 17 
Synthesis of (4S-trans)-4,5-dihydro-2,4-diphenyl-5-vinyloxazoline 
To 927 mg (3 mmol) of 4-(N-benzoyl)amino-4-phenyl-1-acetoxy-2-butene was 
added 50 ml of acetonitrile, 930 mg (6 mmol) of potassium carbonate, and 
172 mg (0.15 mmol) of tetrakistriphenylphosphine palladium 
(Pd(PPh.sub.3).sub.4), in sequence. The mixture was heated to reflux at 
70.degree. C. for 24 hours, and then cooled to room temperature in air. 
After this, the cooled mixture was filtered through a cellite pad, 
concentrated under reduced pressure, purified by column chromatography 
(hexane:ethyl acetate=10:1), thereby obtaining 546 mg (73% yield) of 
(4S-trans)-4,5-dihydro-2,4-diphenyl-5-vinyloxazoline. 
.sup.1 H NMR (CDCl.sub.3) .delta. 4.88(dd, J=7.0, 8.0 Hz, 1H), 5.05(d, 
J=8.0 Hz, 1H), 5.33(d, J=10.5 Hz, 1H), 5.38(d, J=17.5 Hz, 1H), 6.09(ddd, 
J=7.0, 10.5, 17.5 Hz, 1H), 7.31-7.53(m, 8H), 8.08(m, 2H); 
.sup.13 C NMR (CDCL.sub.3) .delta. 76.8, 89.2, 118.6, 127.4, 128.3, 128.4, 
129.1, 129.2, 129.5, 132.3, 136.6, 142.4, 164.7 
EXAMPLE 18 
Synthesis of (4S-trans)-4,5-dihydro-4-benzyl-2-phenyl-5-vinyl-oxazoline 
120 mg (60% dispersion, 3 mmol) of sodium hydride was suspended in 
methylene chloride. To this suspension, a solution of 970 mg (3 mmol) of 
4-(N-benzoyl)amino-5-phenyl-1-acetoxy-2-pentene in 10 ml of methylene 
chloride was slowly added dropwise at 0.degree. C., followed by 172 mg 
(0.15 mmol) of tetrakistriphenylphosphine palladium (Pd(PPh.sub.3).sub.4). 
The mixture was heated to reflux at 35.degree. C. for 24 hours, and then 
cooled to room temperature in air. After this, the cooled mixture was 
filtered through a silica pad, washed with 20 ml of methylene chloride, 
distilled under reduced pressure, purified by column chromatography 
(hexane:ethyl acetate=10:1), thereby obtaining 616 mg (73% yield, 91% 
diastereomeric excess) of 
(4S-trans)-4,5-dihydro-4-benzyl-2-phenyl-5-vinyl-oxazoline. 
.sup.1 H NMR (CDCl.sub.3) .delta. 2.79(dd, J=7.5, 13 Hz, 1H), 3.26(dd, 
J=5.5, 13 Hz, 1H), 4.26(ddd, J=5.5, 7.0, 7.5 Hz, 1H), 4.76(dd, J=6.5, 7.0 
Hz, 1H), 5.06(dd, 2H), 5.72(ddd, 1H), 7.22-7.51(m, 8H), 7.97-8.01(m, 2H); 
.sup.13 C NMR (CDCL.sub.3) .delta. 42.2, 74.5, 84.6, 116.5, 126.5, 128.3, 
128.4, 129.2, 129.5, 131.3, 136.2, 137.5, 163.0 
EXAMPLE 19 
Synthesis of (4S-trans)-4,5-dihydro-4-isobutyl-2-phenyl-5-vinyl-oxazoline 
120 mg (60% dispersion, 3 mmol) of sodium hydride was suspended in 30 ml of 
methylene chloride. To this suspension, a solution of 895 mg (3 mmol) of 
4-(N-benzoyl)amino-6-methyl-1-acetoxy-2-heptene in 10 ml of methylene 
chloride was slowly added dropwise at 0.degree. C., followed by 172 mg 
(0.15 mmol) of tetrakistriphenylphosphine palladium (Pd(PPh.sub.3) 
.sub.4). The mixture was heated to reflux for 24 hours. After this, the 
resulting material was filtered through a silica pad, washed with 20 ml of 
methylene chloride, distilled under reduced pressure, purified by column 
chromatography (hexane:ethyl acetate=20:1), thereby obtaining 515 mg (75% 
yield, 91% diastereomeric excess) of 
(4S-trans)-4,5-dihydro-4-isobutyl-2-phenyl-5-vinyl-oxazoline. 
.sup.1 H NMR (CDCl.sub.3) .delta. 0.98(dd, 6H), 1.41(m, 1H), 1.65(m, 1H), 
1.89(m, 1H), 4.01(dd, J=9.5 Hz, J=7.0 Hz, 1H), 4.63(dd, J=7.0, 1H), 
5.25(d, J=10.5 Hz, 1H), 5.39(d, J=16 Hz, 1H), 5.96(ddd, J=16.0 Hz, J=10.5 
Hz, J=7.0 Hz), 7.39-7.49(m, 3H), 7.95-7.98(m, 2H); 
.sup.13 C NMR (CDCL.sub.3) .delta. 22.6, 22.9, 25.0, 45.2, 70.8, 86.3, 
117.1, 128.0, 128.2, 128.3, 131.2, 136.5, 162.4 
EXAMPLE 20 
Synthesis of 
(4S-trans)-4,5-dihydro-4-cyclohexylmethyl-2-phenyl-5-vinyl-oxazoline 
65 mg (60% dispersion, 2.73 mmol) of sodium hydride was suspended in 15 ml 
of methylene chloride. To this suspension, a solution of 900 mg (2.73 
mmol) of 4-(N-benzoyl)amino-5-cyclohexyl-1-acetoxy-2-pentene in 10 ml of 
methylene chloride was slowly added dropwise at room temperature, followed 
by 312 mg (0.27 mmol) of tetrakistriphenylphosphine palladium 
(Pd(PPh.sub.3) .sub.4). The mixture was stirred at 40.degree. C. for 24 
hours. At the end of the reaction, the resulting material was filtered 
through a silica pad, washed with 20 ml of methylene chloride, distilled 
under reduced pressure, and then purified by column chromatography 
(hexane:ethyl acetate=20:1), thereby obtaining 528 mg (72% yield, 91% 
diastereomeric excess) of 
(4S-trans)-4,5-dihydro-4-cyclohexylmethyl-2-phenyl-5-vinyl-oxazoline. 
.sup.1 H NMR (CDCl.sub.3) .delta. 0.95-0.98(m, 2H), 1.21-1.28(m, 5H), 
1.41-1.44(m, 1H), 1.64-1.72(m, 3H), 1.80(m, 2H), 4.04(dd, J=7.5 Hz, J=7.0 
Hz, 1H), 4.62(dd, J=7.0 Hz, 1H), 5.24(d, J=10.0 Hz, 1H), 5.37(d, J=17.0 
Hz, m 1H), 5.96(ddd, J=17.0 Hz, J=10.0 Hz, J=7.0 Hz), 7.38-7.48(m, 3H), 
7.95-7.97(m, 2H); 
.sup.13 C NMR (CDCL.sub.3) .delta. 26.2, 26.5, 26.6, 33.3, 33.5, 34.3, 
43.7, 70.1, 86.3, 117.0, 128.23, 128.25, 128.26, 131.2, 136.4, 162.4 
EXAMPLE 21 
Synthesis of (4S-trans)-4,5-dihydro-2,4-diphenyloxazoline-5-carboxylic Acid 
30 ml of a mixed solution of acetonitrile/carbon tetrachloride/water 
(1:1:1) was added to 346 mg (1.5 mmol) of 
(4S-trans)-4,5-dihydro-2,4-diphenyl-5-vinyl-oxazoline while stirring at 
room temperature. The mixture was added with 819 mg (9.75 mmol) of sodium 
bicarbonate and 1.76 g (17.25 mmol) of sodium periodate (NaIO.sub.4), and 
then stirred for 5 minutes. Next, about 3 mg of ruthenium chloride, as a 
catalyst, was added thereto, followed by stirring for two days. At the end 
of the reaction, the resulting material was extracted with 20 ml of 
diethyl ether. Following this, a water layer was acidified with 1H HCl, 
and then extracted with methylene chloride, thereby obtaining 317 mg (75% 
yield) of (4S-trans)-4,5-dihydro-2,4-diphenyl-oxazoline-5-carboxylic acid. 
To the obtained product was added 20 ml of diethyl ether, and then 1.0 ml 
of diazomethane dropwise. The resulting mixture was concentrated under 
reduced pressure, thereby to obtain 330 mg of 
(4S-trans)-4,5-dihydro-2,4-diphenyl-oxazoline-5-carboxylic acid methyl 
ester. 
.sup.1 H NMR (CDCl.sub.3) .delta. 3.87(s, 3H), 4.93(d, J=6.5 Hz, 1H), 
5.46(d, J=6.5 Hz, 1H), 7.31-7.57(m, 8H), 8.09-8.12(m, 2H); 
.sup.13 C NMR (CDCL.sub.3) .delta. 53.5, 75.4, 83.9, 127.2, 127.5, 128.8, 
129.2, 129.4, 129.6, 132.7, 141.8, 164.7, 171.4 
EXAMPLE 22 
Synthesis of 
(4S-trans)-4,5-dihydro-4-benzyl-2-phenyl-oxazoline-5-carboxylic Acid 
30 ml of a mixed solution of acetonitrile/carbon tetrachloride/water 
(1:1:1) was added to 395 mg (1.5 mmol) of 
(4S-trans)-4,5-dihydro-4-benzyl-2-phenyl-5-vinyl-oxazoline while stirring 
at room temperature. The mixture was added with 819 mg (9.75 mmol) of 
sodium bicarbonate and 1.76 g (17.25 mmol) of sodium periodate 
(NaIO.sub.4), and then stirred for 5 minutes. Next, about 3 mg of 
ruthenium chloride, as a catalyst, was added thereto, followed by stirring 
for two days. At the end of the reaction, the resulting material was 
extracted with 20 ml of diethyl ether. Following this, a water layer was 
acidified with 1H HCl, and then extracted with methylene chloride, thereby 
obtaining 317 mg (75% yield) of 
(4S-trans)-4,5-dihydro-4-benzyl-2-phenyl-oxazoline-5-carboxylic acid. To 
the obtained product was added 20 ml of diethyl ether, and then 1.0 ml of 
diazomethane dropwise. The resulting mixture was concentrated under 
reduced pressure, thereby to obtain 330 mg of 
(4S-trans)-4,5-dihydro-4-benzyl-2-phenyl-oxazoline-5-carboxylic acid 
methyl ester. 
.sup.1 H NMR (CDCl.sub.3) .delta. 2.89(dd, J=7.1 Hz, 13.9 Hz, 1H), 3.12(dd, 
J=6.1 Hz, J=13.9 Hz, 1H), 3.62(s, 3H), 4.57(dd, J=6.1 Hz, J=7.1 Hz, 1H), 
4.65 (d, J=6.1 Hz, 1H), 7.13-7.43 (m, 8H), 7.88-7.90(m, 2H); 
.sup.13 C NMR (CDCL.sub.3) .delta. 41.5, 52.4, 72.7, 79.5, 126.7, 127.0, 
128.3, 128.4, 128.5, 129.6, 131.6, 136.6, 163.2, 170.8 
EXAMPLE 23 
Synthesis of 
(4S-trans)-4,5-dihydro-4-isobutyl-2-phenyl-oxazoline-5-carboxylic Acid 
30 ml of a mixed solution of acetonitrile/carbon tetrachloride/water 
(1:1:1) was added to 392 mg (1.5 mmol) of 
(4S-trans)-4,5-dihydro-4-isobutyl-2-phenyl-5-vinyl-oxazoline while 
stirring at room temperature. The mixture was added with 819 mg (9.75 
mmol) of sodium bicarbonate and 1.76 g (17.25 mmol) of sodium periodate 
(NaIO.sub.4), and then stirred for 5 minutes. Next, about 3 mg of 
ruthenium chloride, as a catalyst, was added thereto, followed by stirring 
for two days. At the end of the reaction, the resulting material was 
extracted with 20 ml of diethyl ether. Following this, a water layer was 
acidified with 1H HCl, and then extracted with methylene chloride, thereby 
obtaining 286 mg (77% yield) of 
(4S-trans)-4,5-dihydro-4-isobutyl-2-phenyl-oxazoline-5-carboxylic acid. To 
the obtained product was added 20 ml of diethyl ether, and then 1.0 ml of 
diazomethane dropwise. The resulting mixture was concentrated under 
reduced pressure, thereby to obtain 302 mg of 
(4S-trans)-4,5-dihydro-4-isobutyl-2-phenyl-oxazoline-5-carboxylic acid 
methyl ester. 
.sup.1 H NMR (CDCl.sub.3) .delta. 1.00(dd, 6H), 1.51(m, 1H), 1.69(m, 1H), 
1.98(m, 1H), 3.80(s, 3H), 4.35(dd, J=6.0 Hz, J=9.9Hz, 1H), 4.66(d, J=6.0 
Hz, 1H), 7.39-7.52(m, 8H), 7.96-8.00(m, 2H); 
.sup.13 C NMR (CDCL.sub.3) .delta. 22.5, 22.8, 25.0, 45.8, 52.5, 70.5, 
81.1, 127.2, 128.4, 128.5, 131.6, 162.5, 171.2 
EXAMPLE 24 
Synthesis of 
(4S-trans)-4,5-dihydro-4-cyclohexylmethyl-2-phenyl-oxazoline-5-carboxylic 
Acid 
30 ml of a mixed solution of acetonitrile/carbon tetrachloride/water 
(1:1:1) was added to 350 mg (1.3 mmol) of 
(4S-trans)-4,5-dihydro-4-cyclohexylmethyl-2-phenyl-5-vinyl-oxazoline while 
stirring at room temperature. The mixture was added with 819 mg (9.75 
mmol) of sodium bicarbonate and 1.76 g (17.25 mmol) of sodium periodate 
(NaIO.sub.4), and then stirred for 5 minutes. Next, about 3 mg of 
ruthenium chloride, as a catalyst, was added thereto, followed by stirring 
for two days. At the end of the reaction, the resulting material was 
extracted with 20 ml of diethyl ether. Following this, a water layer was 
acidified with 1H HCl, and then extracted with methylene chloride, thereby 
obtaining 278 mg (75% yield) of 
(4S-trans)-4,5-dihydro-4-cyclohexylmethyl-2-phenyl-oxazoline-5-carboxylic 
acid. To the obtained product was added 20 ml of diethyl ether, and then 
1.0 ml of diazomethane dropwise. The resulting mixture was concentrated 
under reduced pressure, thereby to obtain 290 mg of 
(4S-trans)-4,5-dihydro-4-cyclohexymethyl-2-phenyl-oxazoline-5-carboxylic 
acid methyl ester. 
.sup.1 H NMR (CDCl.sub.3) .delta. 0.95-1.05(m, 2H), 1.12-1.34(m, 6H), 
1.47-1.84(m, 5H), 3.80(s, 3H), 4.40(dd, J=6.6 Hz, J=6.9 Hz, 1H), 4.64(d, 
J=6.6 Hz, 1H), 7.39-7.52(m, 3H), 7.96-8.00(m, 2H); 
.sup.13 C NMR (CDCL.sub.3) .delta. 26.2, 26.5, 26.6, 33.2, 33.5, 34.3, 
44.4, 52.5, 69.9, 81.2, 128.4, 128.5, 131.2, 136.4, 165.2, 171.7 
EXAMPLE 25 
Synthesis of 
(4S-trans)-4,5-dihydro-2,4-diphenyl-5-(2-hydroxyethyl)oxazoline 
To 249 mg (1.0 mmol) of 
(4S-trans)-4,5-dihydro-2,4-diphenyl-5-vinyloxazoline was added 10 mg of 
tetrahydrofuran, followed by 6 ml (3.0 mmol) of 9-borabicyclo[3.3.1]nonane 
(0.5M in THF). The mixture was then stirred for 8 hours at room 
temperature. At the end of the reaction, the resulting material was added 
with 2 ml of ethanol, 0.65 ml of 6N NaOH, and 1.3 ml of H.sub.2 O.sub.2, 
in sequence, stirred for 30 minutes, and then extracted with 10 ml of 
ethyl acetate twice. The combined organic layer was washed with 10 ml of 
brine twice, dried with MgSO.sub.4, filtered, and then concentrated under 
reduced pressure. The concentrate was purified by column 
chromatography(hexane:ethyl acetate=1:2), thereby obtaining 222 mg (83% 
yield) of (4S-trans)-4,5-dihydro-2,4-diphenyl-5-(2-hydroxyethyl)oxazoline. 
.sup.1 H NMR (CDCl.sub.3) .delta. 2.05(m, 2H), 3.87(m, 2H), 4.66(m, J=4.9 
Hz, J=7.3 Hz, 1H), 4.96(d, J=7.3 Hz, 1H), 7.26-7.52(m, 8H), 8.02-8.04(m, 
2H) 
.sup.13 C NMR (CDCL.sub.3) .delta. 38.0, 59.5, 75.8, 85.4, 126.7, 127.6, 
127.8, 128.4, 128.5, 128.8, 131.7, 141.9, 163.9 
EXAMPLE 26 
Synthesis of 
(4S-trans)-4,5-dihydro-4-benzyl-5-(2-hydroxyethyl)-2-phenyloxazoline 
To 63 mg (1.0 mmol) of 
(4S-trans)-4,5-dihydro-4-benzyl-2-phenyl-5-vinyloxazoline was added 10 mg 
of tetrahydrofuran, followed by 6 ml (3.0 mmol) of 
9-borabicyclo[3.3.1]nonane (0.5M in THF). The mixture was then stirred for 
8 hours at room temperature. At the end of the reaction, the resulting 
material was added with 2 ml of ethanol, 0.65 ml of 6N NaOH, and 1.3 ml of 
H.sub.2 O.sub.2, in sequence, stirred for 30 minutes, and then extracted 
with 10 ml of ethyl acetate twice. The combined organic layer was washed 
with 10 ml of brine twice, dried with MgSO.sub.4, filtered, and then 
concentrated under reduced pressure. The concentrate was purified by 
column chromatography(hexane:ethyl acetate=1:2), thereby obtaining 231 mg 
(82% yield) of 
(4S-trans)-4,5-dihydro-4-benzyl-5-(2-hydroxyethyl)-2-phenyloxazoline. 
.sup.1 H NMR (CDCl.sub.3) .delta. 1.52 (m, 1H), 1.83 (m, 1H), 2.71 (dd, 
J=9.0 Hz, J=13.5 Hz, 1H), 3.26 (dd, J=5.0 Hz, J=13.5 Hz, 1H), 3.63 (m, 
2H), 4.18(m, J=5.0 Hz, 6.5 Hz, 9.0 Hz, 1H), 4.55(m, J=6.5Hz), 7.23-7.50(m, 
8H), 7.93-7.95(m, 2H) 
.sup.13 C NMR (CDCL.sub.3) .delta. 38.7, 42.5, 60.0, 74.1, 82.6, 127.4, 
128.5, 128.9, 129.0, 129.1, 130.1, 132.1, 138.3, 163.7 
EXAMPLE 27 
Synthesis of 
(4S-trans)-4,5-dihydro-5-(2-hydroxyethyl)-4-isobutyl-2-phenyloxazoline 
To 229 mg (1.0 mmol) of 
(4S-trans)-4,5-dihydro-4-isobutyl-2-phenyl-5-vinyloxazoline was added 10 
mg of tetrahydrofuran, followed by 6 ml (3.0 mmol) of 
9-borabicyclo[3.3.1]nonane (0.5M in THF). The mixture was then stirred for 
8 hours at room temperature. At the end of the reaction, the resulting 
material was added with 2 ml of ethanol, 0.65 ml of 6N NaOH, and 1.3 ml of 
H.sub.2 O.sub.2, in sequence, stirred for 30 minutes, and then extracted 
with 10 ml of ethyl acetate twice. The combined organic layer was washed 
with 10 ml of brine twice, dried with MgSO.sub.4, filtered, and then 
concentrated under reduced pressure. The concentrate was purified by 
column chromatography(hexane:ethyl acetate=1:1), thereby obtaining 161 mg 
(65% yield) of 
(4S-trans)-4,5-dihydro-5-(2-hydroxyethyl)-4-isobutyl-2-phenyloxazoline. 
.sup.1 H NMR (CDCl.sub.3) .delta. 0.98(d, 6H), 1.38(m, 1H), 1.62(m, 1H), 
1.90(m, 2H), 1.97(m, 1H), 3.88(m, 2H), 3.95(m, 1H), 4.44(m, 1H), 
7.39-7.49(m, 3H), 7.92-7.94(m, 2H) 
.sup.13 C NMR (CDCL.sub.3) .delta. 23.4, 23.6, 25.6, 38.8, 46.1, 60.4, 
71.1, 83.7, 128.7, 128.9, 129.0, 131.9, 163.0 
EXAMPLE 28 
Synthesis of 
(4S-trans)-4,5-dihydro-4-cyclohexylmethyl-5-(2-hydroxyethyl)-2-phenyloxazo 
line 
To 269 mg (1.0 mmol) of 
(4S-trans)-4,5-dihydro-4-cyclohexylmethyl-2-phenyl-5-vinyloxazoline was 
added 10 mg of tetrahydrofuran, followed by 6 ml (3.0 mmol) of 
9-borabicyclo[3.3.1]nonane (0.5M in THF). The mixture was then stirred for 
8 hours at room temperature. At the end of the reaction, the resulting 
material was added with 2 ml of ethanol, 0.65 ml of 6N NaOH, and 1.3 ml of 
H.sub.2 O.sub.2, in sequence, stirred for 30 minutes, and then extracted 
with 10 ml of ethyl acetate twice. The combined organic layer was washed 
with 10 ml of brine twice, dried with MgSO.sub.4, filtered, and then 
concentrated under reduced pressure. The concentrate was purified by 
column chromatography(hexane:ethyl acetate=2:1), thereby obtaining 210 mg 
(78% yield) of 
(4S-trans)-4,5-dihydro-4-cyclohexylmethyl-5-(2-hydroxyethyl)-2-phenyloxazo 
line. 
.sup.1 H NMR (CDCl.sub.3) .delta. 0.95-1.00(m, 2H), 1.15-1.31(m, 3H), 
1.37(m, 1H), 1.54(m, 1H), 1.61(m, 1H), 1.65-1.98(m, 8H), 3.88(m, 2H), 
3.98(m, 1H), 4.42(m, 1H), 7.38-7.48(m, 3H), 7.92-7.94(m, 2H) 
.sup.13 C NMR (CDCL.sub.3) .delta. 26.9, 27.3, 34.2, 34.3, 35.0, 38.8, 
44.8, 60.4, 70.5, 83.8, 128.7, 128.9, 129.0, 131.9, 163.0 
EXAMPLE 29 
Synthesis of (4S-trans)-4,5-dihydro-2,4-diphenyloxazoline-5-acetic Acid 
10 ml of a mixed solution of acetonitrile/carbon tetrachloride/water 
(1:1:1) was added to 267 mg (1.0 mmol) of 
(4S-trans)-4,5-dihydro-2,4-diphenyl-5-(2-hydroxyethyl)oxazoline. Then, the 
mixture was added with 546 mg (6.50 mmol) of sodium bicarbonate and 1.18 g 
(5.50 mmol) of sodium periodate (NaIO.sub.4), followed by stirring for 5 
minutes. Next, 33.2 mg of ruthenium chloride, as a catalyst, was added 
thereto, followed by stirring for 24 hours. At the end of the reaction, 
the resulting material was extracted with 20 ml of diethyl ether. 
Following this, a water layer was acidified with 1H HCl, and then 
extracted with methylene chloride, thereby obtaining 275 mg (97% yield) of 
(4S-trans)-4,5-dihydro-2,4-diphenyl-oxazoline-5-acetic acid. To the 
obtained product was added 10 ml of diethyl ether, and then 1.0 ml of 
diazomethane dropwise. The resulting mixture was concentrated under 
reduced pressure, thereby to obtain 286 mg of 
(4S-trans)-4,5-dihydro-2,4-diphenyl-oxazoline-5-acetic acid methyl ester. 
.sup.1 H NMR (CDCl.sub.3) .delta. 2.81(dd, J=5.6 Hz, J=15.8 Hz, 1H), 
2.91(dd, J=7.6 Hz, J=15.8 Hz, 1H), 3.73(s, 3H), 4.91(m, J=5.6 Hz, 6.3 Hz, 
7.6 Hz, 1H), 5.02(d, J=6.3 Hz, 1H), 7.26-7.54(m, 8H), 8.03-8.05(m, 2H) 
.sup.13 C NMR (CDCL.sub.3) .delta. 39.8, 52.0, 75.3, 83.2, 126.7, 127.3, 
127.9, 128.4, 128.6, 128.8, 131.7, 141.4, 163.8, 170.2 
EXAMPLE 30 
Synthesis of (4S-trans)-4,5-dihydro-4-benzyl-2-phenyloxazoline-5-acetic 
Acid 
10 ml of a mixed solution of acetonitrile/carbon tetrachloride/water 
(1:1:1) was added to 281 mg (1.0 mmol) of 
(4S-trans)-4,5-dihydro-4-benzyl-5-(2-hydroxyethyl)-2-phenyl-oxazoline. 
Then, the mixture was added with 546 mg (6.50 mmol) of sodium bicarbonate 
and 1.18 g (5.50 mmol) of sodium periodate (NaIO.sub.4), followed by 
stirring for 5 minutes. Next, 33.2 mg of ruthenium chloride, as a 
catalyst, was added thereto, followed by stirring for 24 hours. At the end 
of the reaction, the resulting material was extracted with 20 ml of 
diethyl ether. Following this, a water layer was acidified with 1H HCl, 
and then extracted with methylene chloride, thereby obtaining 289 mg (98% 
yield) of (4S-trans)-4,5-dihydro-4-benzyl-2-phenyl-oxazoline-5-acetic 
acid. To the obtained product was added 10 ml of diethyl ether, and then 
1.0 ml of diazomethane dropwise. The resulting mixture was concentrated 
under reduced pressure, thereby to obtain 303 mg (98% yield) of 
(4S-trans)-4,5-dihydro-4-benzyl-2-phenyloxazoline-5-acetic acid methyl 
ester. 
.sup.1 H NMR (CDCl.sub.3) .delta. 2.32(dd, J=5.5 Hz, J=16.0 Hz, 1H), 
2.62(dd, J=8.0 Hz, J=16.0 Hz, 1H), 2.79(dd, J=8.0 Hz, J=13.5 Hz, 1H), 
3.22(dd, J=5.5 Hz, J=13.5 Hz, 1H), 3.63(s, 3H), 4.21(m, J=5.8 Hz, 6.0 Hz, 
8.0 Hz, 1H), 4.78(m, J=5.5 Hz, 6.0 Hz, 8.0 Hz, 1H), 7.22-7.50(m, 8H), 
7.92-7.94(m, 2H) 
.sup.13 C NMR (CDCL.sub.3) .delta. 40.6, 42.2, 52.6, 73.7, 80.4, 127.3, 
128.2, 129.0, 129.3, 130.2, 132.2, 138.0, 163.7, 170.9 
EXAMPLE 31 
Synthesis of (4S-trans)-4,5-dihydro-4-isobutyl-2-phenyloxazoline-5-acetic 
Acid 
10 ml of a mixed solution of acetonitrile/carbon tetrachloride/water 
(1:1:1) was added to 247 mg (1.0 mmol) of 
(4S-trans)-4,5-dihydro-4-isobutyl-5-(2-hydroxyethyl)-2-phenyl-oxazoline. 
Then, the mixture was added with 546 mg (6.50 mmol) of sodium bicarbonate 
and 1.18 g (5.50 mmol) of sodium periodate (NaIO.sub.4), followed by 
stirring for 5 minutes. Next, 33.2 mg of ruthenium chloride, as a 
catalyst, was added thereto, followed by stirring for 24 hours. At the end 
of the reaction, the resulting material was extracted with 20 ml of 
diethyl ether. Following this, a water layer was acidified with 1H HCl, 
and then extracted with methylene chloride, thereby obtaining 227 mg (87% 
yield) of (4S-trans)-4,5-dihydro-4-isobutyl-2-phenyl-oxazoline-5-acetic 
acid. To the obtained product was added 10 ml of diethyl ether, and then 
1.0 ml of diazomethane dropwise. The resulting mixture was concentrated 
under reduced pressure, thereby obtaining 240 mg of 
(4S-trans)-4,5-dihydro-4-isobutyl-2-phenyloxazoline-5-acetic acid methyl 
ester. 
.sup.1 H NMR (CDCl.sub.3) .delta. 0.98(d, 6H), 1.41(m, 1H), 1.60(m, 1H), 
1.89(m, 1H), 2.61(dd, J=5.5 Hz, J=16.0 Hz, 1H), 2.77(dd, J=7.5 Hz, 16.0 
Hz, 1H), 3.75(s, 3H), 3.98(m, J=5.5 Hz, J=6.0 Hz, J=8.0 Hz, 1H), 4.67(m, 
J=5.5 Hz, 6.0 Hz, 7.5 Hz, 1H), 7.38-7.48((m, 3H), 7.92-7.94(m, 2H) 
.sup.13 C NMR (CDCL.sub.3) .delta. 23.5, 25.6, 28.0, 40.6, 52.7, 70.9, 
81.6, 128.5, 129.0, 132.0, 162.9, 171.3 
EXAMPLE 32 
Synthesis of 
(4S-trans)-4,5-dihydro-4-cyclohexylmethyl-2-phenyloxazoline-5-acetic Acid 
10 ml of a mixed solution of acetonitrile/carbon tetrachloride/water 
(1:1:1) was added to 287 mg (1.0 mmol) of 
(4S-trans)-4,5-dihydro-4-cyclohexylmethyl-5-(2-hydroxyethyl)-2-phenyl-oxaz 
oline. Then, the mixture was added with 546 mg (6.50 mmol) of sodium 
bicarbonate and 1.18 g (5.50 mmol) of sodium periodate (NaIO.sub.4), 
followed by stirring for 5 minutes. Next, 33.2 mg of ruthenium chloride, 
as a catalyst, was added thereto, followed by stirring for 24 hours. At 
the end of the reaction, the resulting material was extracted with 20 ml 
of diethyl ether. Following this, a water layer was acidified with 1H HCl, 
and then extracted with methylene chloride, thereby obtaining 280 mg (93% 
yield) of 
(4S-trans)-4,5-dihydro-4-cyclohexylmethyl-2-phenyloxazoline-5-acetic acid. 
To the obtained product was added 10 ml of diethyl ether, and then 1.0 ml 
of diazomethane dropwise. The resulting mixture was concentrated under 
reduced pressure, thereby to obtain 293 mg of 
(4S-trans)-4,5-dihydro-4-cyclohexylmethyl-2-phenyloxazoline-5-acetic acid 
methyl ester. 
.sup.1 H NMR (CDCl.sub.3) .delta. 0.89-O.99(m, 2H), 1.14-1.34(m, 3H), 
1.40(m, 1H), 1.55-1.90(m, 7H), 2.60(dd, J=5.5 Hz, J=16.0 Hz, 1H), 2.76(dd, 
J=8.0 Hz, J=16.0 Hz, 1H), 3.70(s, 3H), 4.00(dd, J=6.0 Hz, 1H), 4.66(dd, 
J=6.0 Hz, 1H), 7.38-7.47(m, 3H), 7.92-7.93(m, 2H) 
.sup.13 C NMR (CDCL.sub.3) .delta. 26.8, 27.2, 33.7, 34.2, 40.6, 44.7, 
52.7, 70.2, 81.7, 128.5, 129.0, 132.0, 134.3, 162.9, 171.3 
As apparent from the description above, the process for the preparation of 
the oxazoline compound in accordance with the present invention can be 
carried out using, as the starting material, .alpha.-amino acid, such as 
alanine, valine, leucine, cystein, cyclohexylglycine, cyclohexylalanine, 
phenylglycine, p-hydroxyphenylglycine, phenylalanine, or 
p-hydroxyphenylalanine. Besides this, the process in accordance with the 
present invention allows only one stereoisomer to be selectively 
synthesized in the preparation of (2R, 3S)-N-benzoyl-3-phenylisoserine 
which is a component of a side chain of Taxol, thereby being capable of 
preparing an efficient Taxol side chain and Taxol in a high purity. 
Additionally, the oxazoline compound prepared in accordance with the 
process of the present invention is easily chemically converted to 
.beta.-amino-.alpha.-hydroxy acid or .gamma.-amino-.beta.-hydroxy acid, 
and therefore can be used for the preparation of a physiologically active 
substance. 
Although the preferred embodiments of the invention have been disclosed for 
illustrative purposes, those skilled in the art will appreciate that 
various modifications, additions and substitutions are possible, without 
departing from the scope and spirit of the invention as disclosed in the 
accompanying claims.