JPS6056995A - 23-deoxy-23-oxomycaminosyl tylonolide - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to novel mycaminosyl quilonolide derivatives. 9, Crocodile L
2 is a hydroxyl group or a protected hydroxyl group, R3 is a hydroxyl group or a protected hydroxyl group, and R4 is an aldehyde group.

or a protected aldehyde group.

The same applies hereinafter) 23-deoxy-23-oxo mycaminosyl tylonolide.

As for the protected hydroxyl groups of R1 and R2 in the string.

Hydroxyl groups protected by alkanoyl groups, specifically acetyl groups, globionyl groups, and butyryl groups.

Examples include hydroxyl groups protected with inbutyryl group, valeryl group, invaleryl group, etc., and examples of the protected hydroxyl group of R3 include hydroxyl groups protected with t-butyldimethylsilyl group, tetrahydrofuranyl group, tetrahydropyranyl group, etc. It will be done.

Moreover, as a protected aldehyde group of R4.

Examples include protected saletamonotes in the form of acetals or thioacetals, specifically those protected with dimethyl acetal diethyl acetal, diethylthioacetal ethylene acetal, ethylene thioacetal globylene acetal, and the like.

Compound (I) of the present invention is a novel compound having a chemical structural feature in that the 14th position of mycaminosyl quilonolide is an aldehyde group. The target compound (I) itself exhibits excellent antibacterial activity and is useful as an antibacterial agent, as well as being important as an intermediate for producing a series of mycaminosilta-ylonolide derivatives. Namely.

The aldehyde group at position 14 of the object compound of the present invention is introduced into Nuch's base, hydrazone, etc., an acetal is formed with methanol, ethanol, phenol, etc., or the aldehyde group at position 14 is introduced into an alkylated or arylated alcohol. or further reduce this alcohol.

Alternatively, it can be converted into various useful derivatives by oxidation or amination.

Next, methods for producing the two target compounds of the present invention will be explained.

The target compound (I) has the general formula (I), where R1 and R2 are as described above, R5 is a protected hydroxyl group, and R6 is a protected aldehyde group.

On the side, the hydroxyl group of R8 is the same as the protected hydroxyl group of 11ja, and the protected aldehyde group of Re is the same as the above R
represents the same group as the protected aldehyde group in No. 4. ) It can be produced by oxidizing the compound shown in the following, selectively converting the 14th position into an aldehyde form, and then optionally removing the naked protecting group.

The above oxidation reaction can usually be carried out by reacting compound (n) with pyridinium-trifluoroacetite and N,N-dicyclohexylcarbodiimide in a mixed solvent of anhydrous dimethyl sulfoxide and anhydrous benzene at room temperature. Alternatively, compound (n) can be reacted with pyridinium chloride at room temperature as a dichloromethane solution (the reaction proceeds more quickly by adding pyridine or a molecular sheet).

The protective group can be removed from the obtained reaction product by a conventional method. For example, when the hydroxyl-protecting group is an alkanoyl group such as an acetyl group or propionyl group, the hydroxyl-protecting group can be removed by heating in a methanol or ethanol solution, or by heating in a hydrous alcohol or a hydrous aprotic solvent. When it is a t-butyldimethylsilyl group, it can be easily removed by treatment with tetrabutylammonium fluoride in tetrahydrofuran under cooling or by treatment with hydrofluoric acid. In addition, when the protective group for a hydroxyl group is a tetrahydrofuranyl group or a tetrahydropyranyl group, the protective group for an aldehyde group can be removed using an inorganic acid such as hydrochloric acid or sulfuric acid or an organic acid such as trifluoroacetic acid or trichloroacetic acid. This is done by treatment with acid. Removal of these protecting groups can be carried out in any order and can also be partially removed.

The reaction product is isolated and purified by concentrating the two reaction solutions to dryness under reduced pressure, extracting the residue with a solvent, washing with water and drying, or by conventional methods such as recrystallization and column chromatography.

Can be purified.

When the compound (I') of the present invention thus obtained is used as an antibacterial agent, it can be formulated into tablets, powders, granules, and capsules using conventional pharmaceutical carriers.

It can be prepared into an injection or the like and administered orally or parenterally. Dosage is 10~ per time], OOolT
It is appropriate to administer 1 to 4 times a day.

Next, in order to further explain the present invention, two examples will be described.

Incidentally, since the starting materials used in the examples are new, their production methods are listed as reference examples.

Reference Example 1 0.852 g of mycaminosyl quilonolide diethyl acetal was dissolved in 10 m4 of anhydrous acetonitrile, 0.31 ml of acetic anhydride was added, and the mixture was allowed to stand at room temperature for 210 minutes. The reaction solution was concentrated under reduced pressure and sufficiently azeotroped with 4 ml of toluene until the acetic acid odor disappeared. The obtained residue was extracted with 50mZ of chloroform and extracted with saturated hydrogen carbonate l-I
Jium aqueous solution [20 mt, saturated sodium sulfate aqueous solution 2
0. m7, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 1 g of solid 2',4'-)-0-acetylmycaminosyltylonolide diethyl acetal. This product was used in the next reaction without further purification.

Reference example 2 92', 4" C0-acetyl mycaminosyl tylonolide diethyl acetal 110411t was dissolved in anhydrous N
, N-dimethylformamide was dissolved in 1.04 rnl, and 11 g of imidazole 114 and 1 g of t-7' methyldimethylchlorosilyl 125 rl were added and left at 60"C for 23 hours. The reaction solution was concentrated under reduced pressure, and the obtained Dissolve the residue in 3.4 ml of Chloropol A, wash with saturated hydrogen carbonate twice with 1.7 ml of IJum aqueous solution and twice with 1.7 ml of saturated sodium sulfate aqueous solution, and dissolve with anhydrous sulfuric acid. After drying, it was concentrated under reduced pressure.

This was subjected to silica gel column chromatography (
Kieselgel - 6010g, ) Luene - Ethyl acetate =
3:1) 2',4'-di-0-acetyl-3,23-di-0-1-butyldimethylsilylmycaminosyl quilonolide diethyl acetal 11021T1 was obtained.

This material exhibits the following physical and chemical properties.

Nuclear magnetic resonance spectra (CDCIs) δ (ppm) H number Attribution 0.89 18H3,23-O823-08i (tBu
2.06 6H2', 4'-0-COCH32,34
6HNMe2 4.35 1HH-1' Reference example 3. 214'-di-0-acetyl-3,23-di-ot-
250111 g of butyl dimethylnryl mycaminosyl tylonolide diethyl acetal was added to 57 g of tetrahydrofu
After dissolving in 5.1 ml K, 0.255 ml of a 1 molar solution of tetrabutylammonium fluoride-tetrahydrofuran was added under water cooling, and the mixture was left to stand for 15.5 hours. The reaction solution was concentrated under reduced pressure, and the resulting residue was poured into 10 m of chloroform.
After washing twice each with an IJJ solution and a saturated aqueous sodium sulfate solution.

After drying over anhydrous sodium sulfate, the mixture was concentrated under reduced pressure. The obtained solid was subjected to 7-silica gel column chromatography [2 (Kiesel gel-6012, 5 g, )luene:acetone-
2,5: l) 2',4'-di-0-acetyl-3
129 mt of -0-t-butyl dimethylnryl mica ξ/rutainolide diethyl acetal was obtained.

This product exhibits the same physical and chemical properties.

Nuclear magnetic resonance spectrum (CDC13) δ (ppm) H number Assignment 0.92 9H3-0-8i (0-8i (t Bo3.
05 6H2',4'-OCo C average 2.36 6HN
Me2 4.40 1HH-1' Reference Example 4 2: Dissolve 100 rr of 4'-di-0-acetyl-3-0-t-butyldimethylsilylmaicami, nosyl tylonolide diethyl acetal in 2 ml of methanol.
It was heated at 0r for 24 hours. The reaction solution was concentrated under reduced pressure, and the resulting solid was dissolved in 5 ml of chloroform, washed with a saturated aqueous sodium bicarbonate solution and a saturated aqueous sodium sulfate solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give a solution of 3-0.
-t-Butyldimethyl7lylmycaminosyltylonolide diethylacetal 891+1i was obtained.

This material exhibits the following physical and chemical properties.

Nuclear magnetic resonance spectrum (CDCI) δ (ppm) H number Assignment 0.88 9H3-0-8t (Me)2-tBu2.
53 6 HNMe2 4.30 1HH-1' Example 1 3-0-t-phthyldinotylsilylmica i-inosyl tylonolide diethyl acetal 85rrTg, anhydrous dimethyl sulfoxide 0.85mt, anhydrous benzene 0.85
rnt, 20.9 mg of pyridinium trifluoroacetite and 89.510 g of N,N'-)cyclohexylcarpodiimide were added, and the mixture was left to stand at room temperature for 15 hours. 0.1 rnl of water was added to the reaction solution and filtered. Wash the precipitate with benzene, combine with the filtrate, and add benzene 5
It was made into a ml solution. This was washed twice with 2 mt of a saturated aqueous solution of hydrogen carbonate and 3 times with 2 mt of a saturated aqueous sodium sulfate solution, dried with anhydrous sulfuric acid, and concentrated under reduced pressure. This was subjected to licage gel column chromatography to obtain 6010 g of Kiesel gel (chloroform:methanol:concentrated ammonia water = 10:1:0.1).
, 29.4 ff@ of 3-0-t-butyldimethylsilyl-23-deoxy-23-oxomycaminosyltinolide diethyl acetal was obtained.

This material exhibits the following physical and chemical properties.

Nuclear magnetic resonance spectrum (CDC13) δ (ppm) H number Attribution 0.92 9H30St(Me)2-tBu2.50
6 HNMe2 4.27 1HH-1' 9.71 1HI(-20 Example 2 3-0-t-butyldinothyrunyl-23-deoxy2
20 mg of 3-oxomiminocyltylonolide (diethyl acetate) and 0.1 mZ of acetonitrile.

It was dissolved in 0.1 liter of 10% hydrofluoric acid and left at room temperature for 15 hours.

The reaction solution was adjusted to pH 9 by adding saturated aqueous sodium bicarbonate solution under cooling, and then extracted with 1 cal of chloroform.

This was washed with a saturated aqueous sodium sulfate solution.

After drying over anhydrous sodium sulfate, it was concentrated under reduced pressure. This was subjected to silica gel column chromatography to obtain 602 g of kiesel gel + chloroform:methanol = 7:1).
3.9 mg of 23-deoxy-23-oxo mycaminonerutylonolide was obtained.

This material exhibits the following physical and chemical properties.

Nuclear magnetic resonance spectrum (CDCI) J (ppm) H number Assignment 1.88 3H22Me 2.54 6 HNMe2 3.66 1HH-14 4,271HH-1' 5.30 1HH-15 5, s3 1HH-13 6, 3611(1(-10 7,301HH-11 9,691HI(-23ClO 2,711HH-20CHO Dissolve acetal 301r@ in 0.3 ml of anhydrous benzene and 03 ml of anhydrous dimethyl sulfoxide, and dissolve pyridinium-trifluoroacetitro, 5rrtg, N, N'-
Dicyclohexylcarbodiimide 28.211! g was added and left overnight at room temperature. 3 ml of water was added to the reaction solution, followed by extraction using 3 ml of benzene. Wash the organic layer with saturated sulfuric acid), wash with 2 ml of IJum aqueous solution, and rinse with anhydrous sulfuric acid)
IJJum was dried and concentrated under reduced pressure. This was subjected to silica gel column chromatography to produce 603g of Kiesel gel.
+Toluene-Ethyl acetate = 3:1) 2: 4'-')-0-acetyl-3-0-t-butyldimethylsilyl-23-deoxy-23-oxomyltylonolide diethyl acetal 22.4
mg was obtained.

This material exhibits the following physical and chemical properties.

Nuclear magnetic resonance spectrum (CDCI3) δ (ppm) H number Assignment 0.86 9H30S+(Me)2tBu2.066H
214'-0COC) (a2.35 6 HNMe2 6.36 1HH-10 9,831HH-23 Example 4 2ζ4'-di0-acetyl-3-0-t-butyldimethylsilyl-23-deoxy-23-oxo Mycaminocil tylonolide diethyl acetal 22.3m
g was dissolved in 0.45 ml of methanol and left at 60°C for 6 hours. Concentrate the reaction solution under reduced pressure to 1 ml of chloroform.
IJum aqueous solution,
The mixture was washed successively with saturated aqueous sodium sulfate solution, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure.

Subsequently, it was dissolved in 0.4 ml of acetonitrile and 0.4 ml of 10% hydrofluoric acid and left overnight. A saturated aqueous sodium hydrogen carbonate solution was added to the reaction solution to adjust the pH to 8.

Extracted with 1 ml of chloroform. After washing this with saturated aqueous sodium sulfate solution and drying with anhydrous sodium sulfate,
It was concentrated under reduced pressure. This was subjected to silica gel column chromatography to obtain 602 g of kieselgel and chloroform.
Methanol-7:1) 23-deoxy-23-oxo
Mycaminocil quilonolide 3U@ was obtained.

Reference example 5゜ inn.

2: , i/-di0-acetyl micaminoturu tylonolide 1.2 g of diethyl acetal was added to anhydrous N,
It was dissolved in 12 ml of N-dimethylformamide, 270 Ing of imidazole and 360 ff 1 g of t-butyldimethylsilyl chloride were added, and the mixture was left at 37°C overnight. The reaction solution was concentrated under reduced pressure and azeotropically concentrated with toluene several times.

A 30 ml solution of chloroform was prepared, and this was washed successively with saturated aqueous solutions of sodium hydrogen carbonate and sodium sulfate,
After drying over anhydrous sodium sulfate, it was concentrated under reduced pressure. This was subjected to silica gel column chromatography, and Kieselgel-6060g, cyclohexane-acetone = 7:
1) 4'-di-O-acetyl-23-0-t-butyldimethylsilyl mycaminosyl quilonolide
111 g of diethyl acetal was obtained.

This material exhibits the following physical and chemical properties.

Nuclear magnetic resonance spectrum (CDCI) δ (ppm) H number Attribution 0.05-0.06 6 H23-0-8i (Me)
, -tBuO,899H23-23-0-8t(, -t
Bu2.06-2.07 6H2:4'-o-cocH
.

2.34 6 HNMe.

6.31 1HH-10 7,251HH-11 Elemental analysis value C4, H,, No, 1 St experimental value C:
62.22%H: 8.99% N: 1.42% Calculated value C: 62.14%H: 9.09% N: 1
．． 61% Reference Example 6, Me 2 (4'-di-O-acetyl-23-0-t-butyldimethylsilyl mycaminosyl quilonolide 1 g of diethyl acetal was dissolved in anhydrous dichloromethane 20 m + tK
Dissolve, add 0.35 ml of dihydrofuran and 577 mg of pyridinium-paratoluenesulfonate and heat at 40°C.
I left it for 5 hours and 30 minutes.

Cool the reaction solution with water and half-saturated hydrogen carbonate) +7um aqueous solution 30
ml and add 15 ml of dichloromethane.

The organic layer was separated, further washed with saturated aqueous sodium sulfate solution, and dried over anhydrous sodium sulfate.

It was concentrated under reduced pressure. This was subjected to silica gel column chromatography to obtain 6030 g of Kieselgel, cyclohexane-acetone-10: 1) 214'-di-O-acetyl-23-0-t-butyldinotylzolyl-3-〇-tetrahydrofuranyl mycaminosyl tylonolide diethylacetal 833
ffIg was obtained.

This material exhibits the following physical and chemical properties.

Nuclear magnetic resonance spectrum (CDCl5) δ (ppm) H number Attribution 0.89 9 H23-0-8i (Me)t-tBu
2.05-6 6 H2?4'-ococu.

2.35 6 HNMe.

5.35 1H-'10 7,], 7 1HH-11 Elemental analysis value C4,H,,NO,,SiExperimental value C:
62.50% H: 8.91% N: 1.27
% calculation value C: 62.62% H: 9.05% N:
1.49% Reference Example 7゜214'-di-0-acetyl-23-0-t-butyldimethyl 7ly-3-0-rtrahydrofuranyl mycaminosyl tylonolide diethyl acetal 824
(1 g was dissolved in 16.5 ml of anhydrous tetrahydrofuran, 1.23 ml of a 1 molar solution of tetrabutylammonium fluoride in tetrahydrofuran was added under an ice water bath, and the mixture was left to stand for 1 hour. The reaction solution was concentrated under reduced pressure, and 30 ml of chloroform was added to it. The mixture was washed with a saturated aqueous sodium sulfate solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.This was subjected to silica gel column chromatography to obtain 6045 g of Kieselgel, cyclohexane-acetone (9:1 to 7:2) 2:, i '-Di0-acetyl-3-O-tetrahydrofuranyl mycaminosyl tylonolide diethyl acetal 607■ was obtained.

This material exhibits the following physical and chemical properties.

Nuclear magnetic resonance spectrum (CDCl3) δ (ppm) H number assignment 2.05-6 6 Hz', 4'-ococH.

2.35 6 HNMe! ~5.35 IH cost 0 7.18 1HH-11 Elemental analysis value C43H? INO+4 Experimental value C:6
1.57% H: 8.39% N: 1.78% Calculated value -'-Hho C: 61.87% H: 8.63% N: 1.6
8% Example 5゜2 (4'-di-0-acetyl-3-0-tetrahydrofuranyl mycaminosyl tylonolide diethyl acetal (555,111 g) was dissolved in 5.5 ml each of anhydrous benzene and anhydrous dimethyl sulfoxide, 13 g of fluoroacetite O and 0.55 g of dicyclohexylcarbodiimide were mixed and allowed to stand at room temperature overnight.Benzene was added to the reaction mixture to make a 30 mL solution, and this was mixed with a saturated aqueous solution of 1 sodium bicarbonate.

Wash twice each with 1-5 mZ of saturated sulfuric acid solution.

After drying over anhydrous sodium sulfate, it was concentrated under reduced pressure. This was subjected to silica gel column chromatography using Kieselgel-6027g and cyclohexane-acetone-8:1.
~6:1) Crude 2-4'-di-O-acetyl-23-deoxy-23-oxo-3-0-tetrahydrofuranyl
Mycaminocil tylonolide diethyl acetal 315■ (I asked.

This material exhibits the following physical and chemical properties.

Nuclear magnetic resonance spectrum (CDCl, )δ (ppm)
H number 2.04 to 2.06 6Hz: 4'-ococx (32
,356HNMe2 ~3.60 1)I H-14 9,63~9.65 1HH-23 Example 6゜2te4'-di-0-acetyl-23-deoxy-23-
Oxo-3-0-tetrahydrofuranyl tar 1.90
Dissolve 1Qg in 19 ml of methanol Ie at 50℃
I left it there overnight. The reaction solution was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography to obtain Kiessel gel-6.
09.5g, chloroborum-methanol-28% aqueous ammonia = 30:1:0.1) 23-deoxy-23-
Oxo-3-0-tetrahydrofuranyl mycaminosyl tie O/ride diethyl acetal 71.614
I got g.

This material exhibits the following physical and chemical properties.

Nuclear magnetic resonance spectrum (CDCl, )δ (ppm)
H number assignment 2.56 6 HNMe.

4.33 1HH-1' 9.70 1HH-23 Example 7゜23-deoxy-23-oxo-3-0-detrahydrofuranyl mycaminosyl tylonolyl (゛ 22.6rl1g of diethyl acetal was dissolved in acetonitrile 0.4
The solution was dissolved in 1.2 ml of 5mZO,IN hydrochloric acid and left at room temperature for 1 hour. Add saturated aqueous sodium hydrogen carbonate solution to the reaction solution to adjust the pH to 8, and add 1.5 ml of chloroform.
Extraction was performed. The chloroform layer was washed with a saturated aqueous sodium sulfate solution, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. This was subjected to 7 silica gel column chromatography to obtain 602 g of kiesel gel, chloroform-methanol-28% aqueous ammonia = 20:1:0.
1) 7.8 µ of 23-deoxy-23-oxo mycaminosyl quilonolide was obtained.

Reference example 8゜Dissolve 0.43 g of 4'-teoxymycaminosyltylonolide diethyl acetal in 5 ml of anhydrous acetonitrile, add 0.15 tnl of acetic anhydride, and stir at room temperature to 180 g.
Leave it for a minute. The reaction solution was concentrated under reduced pressure and azeotroped with toluene several times. A solution of the concentrate in 25 ml of chloroform was added to a saturated aqueous sodium bicarbonate solution.

Wash with 10 mL of saturated aqueous sodium sulfate solution, add anhydrous sulfuric acid), dry over IJum, and concentrate under reduced pressure to obtain 2'-0-acetyl-4'-deoxymycinylsilonolide.
Diethyl acetal was obtained. It was used in the next reaction without further purification.

Reference example 9゜2'-0-acetyl-4'-deoxymycaminosyltylonolide 52 mg of diethyl acetal was mixed with anhydrous N,
Dissolved in 0.52 ml of N-dimethylformamide,
57fftgl of imidazole and 6311tg of t-butyldimethylchlorosilyl were added, and the mixture was left at 6oc for 24 hours.

The reaction solution was concentrated under reduced pressure and azeotroped with xylene several times.

A 3 ml solution of the concentrate in chloroform was washed with a saturated aqueous sodium bicarbonate solution and a saturated aqueous sodium sulfate solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

This was subjected to silica gel column chromatography to obtain Kieselgel-605.5g, ) toluene:ethyl acetate=
3:l) 2'-0-acetyl-3,23-di〇-t-
Butyldimethylsilyl-4'-deoxy mycaminosyl tylonolide diethyl acetal 60 mZ was obtained.

This material exhibits the following physical and chemical properties.

Nuclear magnetic resonance spectrum (CDCl3) δ (ppm)
H number Attribution 0.90 18 H3, 23OSt (Me)2-tB
u2.07 3H2'-0-COMe 2.21 6HNMe2 Reference example 10゜2'-〇-acetyl-3.23-di0-1-butyldimethylsilyl-4'-deoxymycaminosyltylonolide Diethylacetal 200 mg was dissolved in 4 ml of tetrahydrofuran, 0.2 ml of a 1 molar solution of tetrabutylammonium fluoride in tetrahydrofuran was added under water cooling, and the mixture was left to stand for 13 hours. The reaction solution was concentrated under reduced pressure, and a solution of the resulting residue in 8 ml of chloroform was washed with 5 ml each of a saturated aqueous sodium bicarbonate solution and a saturated aqueous sodium sulfate solution.

After drying over anhydrous sodium sulfate, it was concentrated under reduced pressure.

202 rllg of the obtained solid was dissolved in 4 ml of methanol and left at 50 tl' for 20 hours. Concentrate the reaction solution under reduced pressure.

A 6 ml solution of the obtained solid in chloroform was added to 311 ml each of a saturated aqueous sodium bicarbonate solution and a saturated aqueous sodium sulfate solution.
After washing with It and drying with anhydrous sodium sulfate.

It was concentrated under reduced pressure.

This was subjected to silica gel column chromatography, Kiesel gel - 6020 g, chloroform - 1 chloride -
Electrical ammonia water = 20: 1: 0.1)
31 area Suha-! 1s- -1-Butyldimethylsilyl-41-deoxy-mycaminosyl tylonolide diethylacetal 161
111 g was obtained. This material exhibits the following physical and chemical properties.

Nuclear magnetic resonance spectrum (CDCl3) δ (ppm)
H number Attribution 0.9U 9H30Si(Me), tBu2.33 6
HNMe2 4.29 1HH-1' Example 8゜3-0-t-butyldimethylsilyl-4'-deoxy
Maikaminotsuru Tyronolide 150111 g of diethyl acetal and 1.5 m of anhydrous dimethyl sulfoxide
l + anhydrous benzene 1.5 ml K iW dissolved, 45 n1 g of pyridinium trifluoroacetate,
N,N'-dinochlorohexylcarbodiimide 197 m
g was added and left at room temperature for 16 hours. Reaction solution K O,2
ml of water was added and the precipitate was filtered. Furthermore, the precipitate was washed with benozeno (・.

Combined with oral fluid to make Pe/Zen 10mti solution, which was diluted with saturated sulfuric acid three times with 5 ml of saturated sodium bicarbonate aqueous solution)
The mixture was washed four times with 5 m7 of IJum aqueous solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained solid was dissolved in 1.5 ml of acetonitrile and 1.5 ml of 10% hydrofluoric acid and left at room temperature for 16 hours.

While cooling, a saturated aqueous sodium hydrogen carbonate solution was added to the reaction solution to adjust the pH to 9, followed by extraction with 10 mt of chloroform. The chloroform layer was washed with a saturated aqueous sodium sulfate solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. This was subjected to silica gel column chromatography and Kiesel gel
60lug, chloroform:methanol=7:1)23
．． 4'-dideoxy-23-oxo mycaminosyl
Quilonolide 18■ was obtained. This material exhibits first-order physical and chemical properties.

Nuclear magnetic resonance spectrum (CDC1a) δ (ppm)
H number Attribution 1.88 3H22--IVIe 2.32 6 HN Me2 4.26 1HH-1' 5.83 1HH-13 6,371HH-10 9,72HH-23 and H-20CHO Patent applicant

Claims (1)

[Claims] (1) General formula (wherein, R1 is a hydrogen atom or a hydroxyl group, or a protected hydroxyl group, R2 is a hydroxyl group or a protected hydroxyl group, R3 is a hydroxyl group or a protected hydroxyl group, and R4 is a hydrogen atom or a protected hydroxyl group) or a protected aldehyde group). (212',4'-di-0-acetyl-3-0-t-buterdinotylsilyl-23-deoxy-23-oxo mycaminosyltylonolide diethyl acetal) according to claim 1. Compound.