JPS6366174A - Production of (3r,4s,5r)-3-amino-5-methyl-5-pentanolide-4-carboxylic acid and salt thereof - Google Patents

Abstract

PURPOSE:To synthesize the titled compound useful for the synthesis of thienamycin, in high selectivity of the desired antipode in high yield, by a chiral synthetic process comprising the reaction of a specific compound with a halogenation agent, etc., followed by the treatment with an acid. CONSTITUTION:A compound of formula I (CO2R<1> is carboxyl which may be esterified) is made to react with a lithiation agent and then with a compound of formula II (CO2R<2> is CO2R<1>; SR4 is mercapto which may be protected) to obtain a mixture of the compounds of formula III and formula IV. The compound of formula III is optionally separated from the mixture and treated with an acid to obtain a mixture of the compounds of formula V and formula VI. The compound of formula V is optionally separated from the mixture and made to react with a base to effect the inversion to a steric configuration. The obtained compound of formula VII is treated with a halogenation agent or an oxidizing agent and the obtained compound of formula VIII is treated with an acid to obtain the objective compound of formula IX (X<-> is anion originated from the acid).

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application]
, 48,5R)-8-Amino-5-methyl-5-pentanolido-4-carboxylic acid (I).

[Conventional technology]

The stereoselective total synthesis of chenamycin via lactone (I) is described in the literature Tetrahedron Letters Vol. 22, 913.
(1981).

[Problem that the invention seeks to solve]

However, since the method of this prior document produces racemic (I), it is necessary to divide and separate and purify one desired diagonal. Therefore, the other unneeded normal body has to be discarded, so the overall defeat rate is less than 50%. The present invention was made to solve the above problems,
The purpose is to provide a method for selectively synthesizing only one desired compound.

[Means for solving problems]

The entire reaction route of the present invention is as follows.

(First invention) The first invention of the present application provides a compound SI't8 of the following formula [wherein co2 and 002] represent a carboxyl group that may or may not be esterified, and 5IL8 represents a mercapto group that may or may not be protected. A compound of the following formula 6o2⇠1 [wherein C02⇠1 and CO2R2 are as defined above] is obtained by treatment with a halogenating agent or an oxidizing agent, and then treated with an acid. (3 几, 48,5 几)-3-Amino-5-methyl-5
- A method for producing pentanolide-4-carboxylic acid and its salt.

R1, R2 and 3 are hydrogen, linear, branched or cyclic Cl-10 alkyl groups (e.g. methyl, ethyl,
Preferred are propyl, isopropyl, butyl, 5eC-butyl, pentyl, heptyl, cyclohexyl, etc.), aralkyl groups (eg, benzyl, phenethyl, etc.), and phenyl groups. These hydrocarbon groups may be substituted with appropriate substituents (e.g., carboxyl groups, alkoxycarbonyl groups (e.g., methoxycarbonyl, ethoxycarbonyl, etc.), amine groups, alkyl-substituted amino groups (e.g., methylamino, ethylamino, jethylamino, etc.),
Hydroxyl group, alkoxy (e.g. methoxy, ethoxy, etc.)
, alkylsilyl groups (e.g., trimethylsilyl, triethylsilyl), acyloxy (e.g., acetyloxy, propionyloxy, etc.), halogen (e.g., chlorine, bromine, iodine, etc.), carbamoyl group, mercapto group, nitrile, nitro group], etc. You may do so.

<Conversion from (8) to (9)> This reaction is carried out in a small amount or an equal amount of Preferably, it is carried out in the presence of water.

As the halogenating agent, bromine, chlorine, N-bromosuccinimide, N-chlorosuccinimide, and (1),3-dibromo-5,5-dimethylhydantoin are preferred.

As the oxidizing agent, nitric acid and ceric ammonium are preferred.

The reaction is carried out at a temperature of 0 to 100°C for 1 minute to 24 hours.

<Conversion from (9) to (I)> As the acid, hydrochloric acid, sulfuric acid, etc. are used.

The reaction is carried out in an aqueous solution by treatment at a temperature of 20-110° C. for 1-48 hours.

(Second invention) The second invention of the present application provides a compound of the following formula [wherein CO2R1, C02It2 and 5rt8 are as defined above] by reacting with a base.
The configuration of the position is inverted to form a compound of the following formula o2itt [wherein CO2R1, co2rt2 and SR8 are as defined above], which is then treated with a halogenating agent or an oxidizing agent to form a compound of the following formula [ wherein CO2R1 and CO2R2 are as defined above] and then treated with an acid.
, 48.51) A method for producing -8-amino-5-methyl-5-pentanolide-4-carboxylic acid and a salt thereof.

<Conversion from (6) to (8)> The inversion reaction can be performed, for example, with sodium carbonate, potassium carbonate,
In the presence of a base such as sodium hydroxide, potassium hydroxide, sodium methylate, sodium ethylate, potassium t-butoxide, methanol, ethanol, t
- In a solvent such as a lower alcohol such as butanol, aqueous acetone, acetonitrile, T I (F), 25° to 100°
This is done by treatment for 10 minutes to 24 hours at a temperature of 'C.

Moreover, when the mixture of (6) and (7) is treated in the same way, (
A mixture of 8) and unreacted (7) is obtained. Separation of (8) from this mixture can be easily carried out by column chromatography or the like.

<Conversion from (8) to (I)> This is the same as the first invention of the present application.

(Third invention) The third invention of the present application provides a compound of the following formula [wherein, 002111. (302R2 and 8R8 are 9 as defined above) is treated with an acid to form a compound of the following formula CO2
几1 [In the formula, C102I'tl, 002R2 and 8R3
is as defined above], and then the steric configuration at the 5-position is inverted by the action of a base to form a compound of the following formula [wherein CO2R1, CO2It2 and SR8 are as defined above], and then this is treated with a oxidizing agent or an oxidizing agent to obtain a compound of the following formula 02R1 [wherein CO2111 and CO2I2 are as defined above], which is then treated with an acid, where X is as defined above] (3R,
4S,5R)-3-amino-5-methyl-5-pentanolide-4-carboxylic acid and its salt.

<Conversion from (4) to (6)> As the acid, 0.01 to 2 times the amount of sulfuric acid, hydrochloric acid, perchloric acid, trifluoroacetic acid, p-++-luenesulfonic acid, etc. are preferable.

The reaction C is carried out in a solvent such as dichloromethane, dichloroethane, chloroform, benzene, ethyl acetate, ether, TII F, etc. at a temperature of 0 to 50°C.

When the mixture of (4) and (5) is treated in the same manner, the mixture of (6) and (7) is obtained. From this mixture (6)
Separation and production of is easily carried out by column chromatography or the like.

<Conversion from (6) to (I)> This is the same as the second invention of the present application.

(Fourth invention) The fourth invention of the present application provides that after treating a compound H of the following formula [wherein CO2R1 is as defined above] with a lithiation agent, a compound of the following formula 88CH=CH-CH=N-COOR2 [In the formula, CO
2R2 and SR8 are as defined above] to form a mixture of the compound CO2R100211 of the following formula [wherein CO2R1,002R2 and 81L8 are as defined above], and (4) is separated from this mixture, or (7) [wherein CO2R1, CO2R2 and 8 几8 are as defined above] by treatment with an acid without oxidation, and from this mixture (6) is separated or separated. The configuration of the 5-position of the compound (6) is inverted by the action of a base to form a compound of the following formula [wherein CO2R1, CO2R2 and SR'' are as defined above], and then this is treated with a halogenating agent or an oxidizing agent to form a compound do2 skin 1 of the following formula [wherein CO2 几l and (302R2 is 9 as defined above]], and then treated with an acid. , represented by the formula [wherein X is as defined above] (8R, 4
This is a method for producing 8,5)-3-amino-5-methyl-5-pentanolide-4-carboxylic acid and its salt.

<Conversion from (2) and (3) to (4) and (5)> As the lithiation agent, lithium diisopropylamide, lithium bis(trimethylsilyl)amide, lithium N-t-butylcyclohexylamide, lithium 2.
2,6,6-titramethylpiperidide is preferred.

The reaction is carried out by mixing (R)-3-hydroxy acetic acid ester (3) in a dry solvent such as ether, THF, 1,2-dimethoxyethane, dioxane, etc. at a temperature of -78°C to 2°C of the lithiation agent. After treatment with 2.5 times the amount for 10 minutes to 5 hours, compound (2) prepared by the method described below [in the formula, CO2
R2 and SR8 are T as defined above.
A solution dissolved in the same solvent used for the reaction such as HF,
This is carried out by treatment at a temperature of -78°C to 5°C for 10 minutes to 5 hours.

The product is a mixture of two isomers (4) and (5), and these two compounds can be separated by column chromatography. However, since only the desired isomer can be easily separated and purified in the subsequent step (6) or (8), the mixture is used in the next step without separating (4) and (5). be able to.

Production of Compound (2)> Hexamethyldisilazane and n-butyllithium are treated in a solvent such as ether, THF, hexane, or pentane at a temperature of -78 to 25°C for 10 minutes to 24 hours according to a conventional method. The prepared solution of lithium bis(trimethylsilyl)amide is treated with 1 equivalent of (1) at a temperature of -78 DEG to 80 DEG C. for 10 minutes to 24 hours. Next, add 1 to 2 times the amount of chlorotrimethylsilane and heat at -78 to 40℃ for 30 to 48 minutes.
After stirring for an hour, the reaction is carried out by treating with 1 to 1.5 times the amount of R20COO] [wherein CO2R2 is as defined above] at a temperature of -78 to 30°C for 10 minutes to 58 hours. The desired compound (2) can also be obtained by adding chlorotrimethylsilane.

<Conversion from (4) to (I)> This is the same as the third invention of the present application.

〔Example〕

Hereinafter, the present invention will be explained in detail with reference to Examples.

Reference Example I Production of N-methoxycarbonyl(2-phenylthio)ethynylcarboxaldimine R8=06H5) Anhydrous TI (1.1, l, 8, 8 in F50mj')
．． Processing 9.8m/8-hexamethyldisilazane,
Cool this to -78℃ 1. 80 mf of 5M n-butyllithium-hexane solution was added dropwise, and the mixture was stirred at the same temperature for 1 hour.

Then (2-phenylthio)ethynylcarboxaldehyde (1, R8=061(5) 6.94
A solution of 1/2 dissolved in anhydrous THFIQmJ was slowly added dropwise, and the mixture was further stirred at -78°C for 1 hour. After adding 6.44 ml of chlorotrimethylsilane and gradually raising the temperature to room temperature, next 8.92 ml of methyl chloroformate!
was slowly added dropwise under ice cooling, and the reaction solution was left in the refrigerator overnight. The reaction solution was concentrated to dryness under reduced pressure, the residue was extracted with methylene chloride, and the extract was concentrated under reduced pressure to obtain crystals of the target product.
II was obtained.

mp, 126-129℃ Elemental analysis value C11) Theoretical value as 111NO28:
C, 59,72; H, 5,01; N, 6.33 Experimental value: C, 59,58: H, 4,98: N, 6.8
8'H-NMR (CDC1a) δ 8.68 (8H
,S).

6.05 (IH, dd, J=5.0, 7.9Hz).

7.38 (5T (, m), 7.46 (1, EI, d, J
=7.911z), 8.44 (LH,d, J
=5.0 ratio) Example 1 Methyl 2-(几)-(1-(R)-hydroxyethyl)-3-methoxycarbonylamino-5-phenylthio-5-pentenoate (4, B1=R2=OH3,R8
=05H5) and (5, R1=R2=CTrB, j
L8: Production of C6T (5) Lithium diisopropylamide prepared from n-butyllithium and diisopropylamine according to a conventional method 0.068 mol THF
(100TR) solution was cooled to -78°C and added 5% of methyl(R)-8-hydroxybutyrate to it under an argon atmosphere. q was added dropwise. After stirring at the same temperature for 1 hour, N-methoxycarbonyl(2-phenylthio)ethynylcarboxaldimine (2, R2 = CIIB, 几8 = 06T
T5) A solution of 9.2y dissolved in 100 mJ of anhydrous THF was slowly added dropwise. After stirring for an additional hour at -78°C, 5.1 ml of acetic acid! and dilute the reaction solution with 200% water.
ml and extracted with ethyl acetate. Wash the extract with water,
After drying (MgSO4) and evaporation under reduced pressure, the desired product was obtained as a crude oil. This product can be used in the following step without further purification, but when purified by column chromatography on silica gel (4,11=R2=CH
3, R8=c6u, ) and (5, R1=R2=CH
3,l1L8=06. A 2=1 mixture of II5) is obtained.

II-I-NMR (CD(,/a) δ 1.28
(8Tl, d.

J=6.5l-12), 2.57(2/8H, dd, J
=3.1, 6.7Hz), 2.68 (1/8T
I, m).

8.72 (6i-I, s), 4.07 (III, m).

4.60 (1/3T(,m), 4.74 (2/
8TI.

m), 5.61-5.80 (2H, m), 6.42 (1
/8H, d, J= 15.0Hz),
6.46C2/811. d, J=15.0 田), 7
．． 24-7, 40 (5■, m) Example 2 (4R, 5L, 6R)- and (48,5R).

6R)-5-methoxycarbonyl-4-methoxycarbonylamino-6-methyl-1-phenylthiotetrahydropyran (6: R' = R2 = CH8.

几a=c6H5) and (7: R1= R2=CH3
, R8=0131 (5) (4, R1=■2 = CH8, Ra=c6u5) and (5, R1=几2=OH3, 几3=CeH5)
11.0.9 of a 2=1 mixture of methylene chloride 200
ml! Hydrogen chloride gas was passed through this solution for 10 minutes while cooling with water, and then the solution was left at room temperature for 1 hour. The reaction solution was washed with saturated aqueous sodium bicarbonate and then evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and from the benzene-ethyl acetate 10:1 eluate, (7゜'PLl = B2
= OH8, t'ta=c6u5) crystal 2.1yI
H-NMR (CDC13) δt, 27 (8Ir,
d.

J=6.0Hz), 1.81 (1'rI,
m), 2.82 (in, m), 2.55 (II
l, dd,, y=4.0, 10.7), 8.6
4 (3Ti, S).

8.68 (8I(,S), 8.98(IH,m).

4.27(IH,m), 4.98(II(,d,,T=
11.6 ta), 5.42 (IH, m),
7.24-7.50 (5H, m) and (6, R1=R2= OH8, n, a=c6r
5.6 g of crystals of u5) were obtained.

mpl 82-141℃ IR(C!I(20J2)84B0,1727,15
LoCm-'I H-NMR (CDC18) δt
, 22 (12/7II.

d, J=6.6 ratio), 115 (9/7II, d.

J=6.6Hz), 2.02 (III, m), 2.8
4(8/7I(, ddd, J=12.8, 12.8゜1
2.3 ratio), 2.78 (4/7IT, ddd, J=1
8.2, 1 B, 2, 6.21), 2.86 (8
/7H, m), 3.01 (IIl, m), 8.71 (6
T.I.

S), 8.77 (3/7H, m), 4.08 (3/7H
,m), 4.29(4/7I(,m), 4.68(4,
/7i-1,m), 4. ．． 8o (8/7I(, dd
.

J=2.4, 12.3Hz), 4.94
(4/7H.

broad d, , T=8.0l-1z)
, 5.07 (3/7H.

broad d, J=8.9l-1z), 5.
76 (4/7H.

d, J=6.217), 7.24-7.50
, (5H.

m) Example 3 (41”t, 58.6R)-5-methoxycarbonyl-
4-methoxycarbonylamino-6-methyl-1-phenylthiotetrahydropyran (8, R1= ]'L2
= CH8, 几32C6H3) production (41,5R,6
R)-5-methoxycarbonyl-4-methoxycarbonylamino-6-methyl-1-phenylthiotetrahydropyran (61R'= R2= CH8, R8=C
6I(5) 6. 1M sodium methylate-methanol solution in 1.50 mJ of anhydrous methanol of OI
11V was added and heated under reflux for 2 hours. After cooling, 2 ml of acetic acid was added, the solvent was distilled off under reduced pressure, and the residue was extracted with methylene chloride. The extract was washed with water and dried (M, g8 (J4
) After concentration under reduced pressure, the residue was crystallized from a small amount of methanol to obtain crystals 4.58.9 of the target product as a mixture of 1-(几) isomer and 1-(S) isomer.

mT), 159-161° [α]n +89° (CC158, C!TI(!I!
a) IR (OH2CI!2) 8440, 1740.1
515 cm-' When this mixture was repeatedly purified by silica gel column chromatography, the benzene-ethyl acetate 10=1 eluate yielded C1-(R) isomer and 1-(S
) A pure product of the isomer was obtained.

1- (S) isomer in-NMn, (ODcJa) δ 1.26 (81
T,,d.

J = 6.11 hairs”), 1.49 (II:I
, dd, , T=11.7, 24.4Hz),
2.17 (LIT, t.

J=10.2l-1z), 2.40(III, m).

8.69 (6H, S), 8.75 (IT, m).

4.07 (IT(, m), 4.70 (III, m).

4.88 (IH, d, J=10.2Hz),
7.25-7.50 (5H, m) 1- (1't) isomer IT (-NM 几(cDcla) δ 1.19 (8H
,d.

J = 6.21 hair), 2.0 (IH, m), 2.80
(11(,,m), 2.87 (I I(,m
).

8.73 (6H, S), 4.25 (IH, m).

4.60 (in, m), 4.67 (IH, m).

5.68 (III, d, J=5.2) (z)
, 7.24-7.50 (5H, m) Example 4 (8R,48,5R) -4-methoxycarbonyl-3
-Production of -methoxycarbonylamino-5-methyl-5-pentanolide (9,11=R2=OH8) (4R,58,68)-5-methoxycarbonyl-4-
Methoxycarbonylamino-6-methyl-1-phenylthiotetrahydropyran (8, R1= R2= CT-
Ta, 几8=06H5) 4.69 with acetonitrile 50mj? ■, 3-dibromo 5,
5-Dimethylhydantoin 11.5. ! il' and 20%
40ml of hydrated acetonitrile! suspension and stirred for 5 minutes. At this time, the reaction temperature rises to about 45°C. 50 r of saturated sodium sulfite aqueous solution in which the reaction solution was cooled in advance
The mixture was poured into R and extracted with ethyl acetate.

The extract was washed with water, dried (M, g804), and then concentrated under reduced water. 50 mT7 of benzene was added to the residue, insoluble materials were removed by filtration, and the filtrate was purified by silica gel column chromatography. Crystals 2.6I of the desired product were obtained from the benzene-ethyl acetate 2:1 eluate.

mp94-95℃ [α:], +11.3°(c O,94, Mea
n) Elemental analysis value Theoretical value as C1, H15NO6:
C, 48,97; IT, 6.17; N, 5.7
1 Experimental value: C, 48,95; II, 6.05;
N, 5.72IR (CH2Cf2) 3440.1740
cm-'IH-NM几CCDC15) δ 1.89
(8yr, d.

J = 6.2 田), 2.68 (I II,
cl d, , T = 7, 8, 17.3 Hz)
, 2.70 (I IT , dd , , 1=
9.8, io, 4Hz), 8.01 (LIT, dd.

J=6.9, 17.81 (z), 8.76 (6
111,S)+4.86(IH,m),4.50(I
II, m).

5.7 5 (LH,m) Example 5 Isopropyl 2-(几)-(1-(R)-hydroxyethyl)-8-(R,8)-methoxycarbonylamino-5-phenylthio-5-pentenoate ( 4, R1
= i -C3H7, R2=CHB, R8
=C6H5) and (5, R1= i -cB■7,
Preparation of (4, R1=i-C8■7
+ R2=CH3, 几3=C6H5) and (5°R'
=i-03IT7. A 6z1 mixture of R2=CH3, R"=06H5) was obtained.

I It-NaR(cncla) δ 1.22-1
．． 88 (9T-T, , m), 2.50 (6
/7H, dd, J=2.8.

6.4) 1z) , 2.56 (1/7H, m
), 8.6 6 (3H, s), 4.05 (LH
, m), 4.60 (1/7H, m), 4.74 (6/
7H, m).

5.02 (1/7H, m), 5.08 (6/7
H, m).

5.65 (LH, m), 5.78 (6/7H
, dd.

J=6.5, 15.0l-1z), 5.
79 (1/7 IT, m).

6.42 (1/7H, dd, J=1.2 .15.01
-1□).

6.45 (6/7H, dd, J=1.0, 15.0Hz
).

7,20 -7.45 (5I(,m)Example 6 (4R,58,6L)-5-isopropoxycarbonyl-4-methoxycarbonylamino-6-methyl-1-phenylthiotetrahydropyran (8, R1= i −C
3H7, R2=Cn3, 几a=061-I5)
Production of isopropyl 2-(R)-(1-(几)-hydroxyethyl) obtained in Example 6 in the same manner as in Example 2
-1-(R,S)-Methoxycarbonylamino-5-phenylthio-5-pentenoate is treated with hydrogen chloride gas (6,It1=i-C8TI7°R2=CH3
, R8=C6H5) and (7, It'=i-C2H4
, R2=CH3, 几8-06T■s) was obtained with a yield of 79%.

This mixture was treated with sodium methylate in the same manner as in Example 3, and the product was purified by silica gel column chromatography to yield the target compound as a mixture of 1- (R) and 1- (S) isomers. % yield.

1- (R) isomer; “T(--NMR(CDOrg) δ 1.19(8
H,d.

J = 6.2 ta), 1.24 (FH, d, J = 6.2
), 1.25 (8H, d, J = 6.2an).

1.99 (IH, m), 2.24 (in, m).

2.86(II(,m), 3.64(BT(,S).

4.24 (LH, m), 4.56 (IH, m).

4.79(II(,m), 5.06(II(,m).

5.68 (ITJ, d, J=5.8t), 7
．． 20-7.50 (5H, m) t -(S)-isomer: IH-NMR (CDCI!3) δ 1.20 (8H, d
.

J=6.0), 1.21 (8H, d, J=
6.1Hz), 1.27 (3H, d, J
= 6.1 ta).

1.49(IT(, dd, J=24.4, 11.9Hz
), 2.12(4I(,t, J=10.5t)
.

2.88 (IH, m), 8.62 (8'FT, 8).

: 11.78 (1) I, m), 4.10 (IT-T, m
).

4.82 (11(,m), 4.84 (
ITT, d.

J=1 1.9l-(z), 5.08 (LIT, m
).

7,24 -7.50 (5H,m) Example 7 (8R,48,5R)-4-isopropoxycarbonyl-3-methoxycarbonylamino-5-methyl-5-pentanolide (9,■1=i- C8■7゜R2=CH3)
Production example (4R, 5
1- (R) isomer and 1- of 8,6R)-5-isopropoxycarbonyl-4-methoxycarbonylamino-6-methyl-1-phenylthiotetrahydropyran
The mixture of (S) isomers was treated with 1°8-dibromo-5,5-dimethylhydantoin to obtain the desired compound in 87% yield.

mp 90-91℃ [α] +12.8° (C0,06, Me□IT)
IH-NMRCCDC18') δ 1.26 (8r
T, d.

J=6.2Hz), 1.27 (8H, d
, J=6.2Hz), 1.4.0 (8
H, d, J = 6.2).

2.60 (2T(, m), 8.03 (ITJ, dd.

J=6.7, 17.317), 3.67(8I(,S)
.

4. 82 (IH, m), 4. ．． 49 (LH, m).

5,05 (2H, m) Poultry Example 8 (3 liters, 48,5 liters) -3-amino-4-carboxy-
Production of 5-methyl-5-pentanolide (I) (8 bottles, 48.5R)-4-methoxycarbonyl-8-
1.2 g of methoxycarbonylamino-5-methyl-5-pentanolide and 50 ml of concentrated hydrochloric acid! The mixture was heated under reflux for 8 hours. Concentrated hydrochloric acid was distilled off at 60°C under reduced pressure, and the residue was dried at 60°C under reduced pressure and then treated with acetone-ether to obtain 0.69 g of the desired hydrochloride.

Claims (4)

[Claims] (1) Compound of the following formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (8) [In the formula, CO_2R^1 and CO_2R^2 are carboxyl groups that may or may not be esterified, and SR^3 is a mercapto group that may or may not be protected. ] is treated with a halogenating agent or an oxidizing agent to form a compound of the following formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (9) [wherein CO_2R^1 and CO_2R^2 are as defined above]. There are formulas ▲ mathematical formulas, chemical formulas, tables, etc. ▼ (1) [wherein, X^- represents an anion derived from the acid], which is characterized by treating this with an acid (3 , 4S, 5R)-3-amino-5-methyl-
A method for producing 5-pentanolide-4-carboxylic acid and a salt thereof. (2) Compound of the following formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (6) [In the formula, CO_2R^1, CO_2R^2 and SR^
3 is as defined above] by reacting with a base to invert the configuration of the 5-position to form a compound of the following formula ▲ Formula,
There are chemical formulas, tables, etc.▼(8) [In the formula, CO_2R^1, CO_2R^2 and SR^
3 is as defined above] and then treated with a halogenating agent or an oxidizing agent to form a compound of the following formula ▲ Numerical formula, chemical formula, table, etc. ▼ (9) [In the formula, CO_2R^1 and CO_2R^ 2 is as defined above] and then treated with an acid. There are formulas ▲ mathematical formulas, chemical formulas, tables, etc. shown (3R
, 4S, 5R) -3-amino-5-methyl-5-pentanolide-4-carboxylic acid and a salt thereof. (3) Compound of the following formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (4) [In the formula, CO_2R^1, CO_2R^2 and SR^
3 as defined above] is treated with an acid to form a compound of the following formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (6) [In the formula, CO_2R^1, CO_2R^2 and SR^
3 is as defined above], and then by inverting the steric configuration at the 5-position by acting with a base, a compound of the following formula ▲ Numerical formula, chemical formula, table, etc. ▼ (8) [In the formula, CO_2R^ 1, CO_2R^2 and SR^
3 is as defined above] and then treated with a halogenating agent or an oxidizing agent to form a compound of the following formula ▲ Numerical formula, chemical formula, table, etc. ▼ (9) [In the formula, CO_2R^1 and CO_2R^ 2 is as defined above] and then treated with an acid. There are formulas ▲ mathematical formulas, chemical formulas, tables, etc. shown (3R
, 4S, 5R) -3-amino-5-methyl-5-pentanolide-4-carboxylic acid and a salt thereof. (4) Compound of the following formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (3) After treating [in the formula, CO_2R^1 is as defined above] with a lithiation agent, a compound of the following formula R^3SCH= CH・CH=N・COOR＾2(2) [
In the formula, CO_2R^2 and SR^3 are as defined above] By reacting with the compound of the following formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (4) + ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ ( 5) [In the formula, CO_2R^1, CO_2R^2 and SR^
3 is as defined above], and from this mixture, (4) is separated or treated with an acid without separation to form a compound of the following formula ▲ Numerical formula, chemical formula, table, etc. ▼ (6) + ▲ There are mathematical formulas, chemical formulas, tables, etc.▼(7) [In the formula, CO_2R^1, CO_2R^2 and SR^
3 is as defined above], and from this mixture, (6) is separated or without separation, the configuration of the 5-position of compound (6) is inverted by the action of a base, and the following formula is obtained: Compound ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (8) [In the formula, CO_2R^1, CO_2R^2 and SR^
3 is as defined above] and then treated with a halogenating agent or an oxidizing agent to form a compound of the following formula ▲ Numerical formula, chemical formula, table, etc. ▼ (9) [In the formula, CO_2R^1 and CO_2R^ 2 is as defined above] and then treated with an acid. There are formulas ▲ mathematical formulas, chemical formulas, tables, etc. ▼ (I) [wherein X is as defined above]. (3R, 4
A method for producing S,5R)-3-amino-5-methyl-5-pentanolido-4-carboxylic acid and a salt thereof.