JPS61172882A - Production of pyranonaphthohydroquinone compound - Google Patents

Abstract

PURPOSE:To produce the titled compound useful as a synthetic raw material of a compound having naphthoquinone structure such as nanaomycin D, etc., by reacting a specific compound having the principal part of the skeleton of nanaomycin with a specific compound. CONSTITUTION:The compound of formula II or formula III can be produced by reacting the compound of formula I (R6 and R7 are -CH3 or -C2H5; R2-R5 are -H, -OCH3 or -OC2H5) with the compound of formula (Ph)3P=CHCOOR1 (R1 is same as R6) or the compound of formula (R1O)2P(=0)CH2COOR1. Nanaomycin D and kalafungin can be produced in high optical purity from the compound of formula II and the compound of formula III, respectively. The reaction is carried out in a solvent such as toluene, benzene, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION Background of the Invention Technical Field The present invention relates to a synthetic raw material for compounds having a pyranonaphthoquinone structure, such as nanaomycin D1, nanaomycin A1, and the like (hereinafter sometimes referred to as nanaomycin, etc.). The present invention relates to a method for producing pyranonaphthohydroquinone compounds useful as pyranonaphthohydroquinone compounds.

Nanaomycin D (δmura, at, ml,:
J, Chem, Soc.

CheTIP Commun,, j 20 (/ri7
6)), Nanaomycin A (δmura, at, a1
．． : J, Antlblot,, 27 JA! (/
Ri7su, Tanaka et al,: 1b
ld,, 21 r40 (/ri7ri, Tan
aka st.

al,: 1bld,, 21.14! (/ri7j)
) and Karafungin (B@rgy: J, Ant
lbiot,, J/ 14134F (/riat))
is a useful antibiotic with antibacterial activity that was discovered in cultures of actinomycetes. All of these are optically active compounds with a bitesoteftoquinone structure, and nanaomycin D is an enantiomer of carafungin.
).

Prior Art Since these are useful antibiotics, attempts have already been made to chemically synthesize them.

(1) K11laon, FLH,: J, Am,
Cham, Sac, 1006263 (/7F), (2) 5outh, M, S, at, al,
: J, Axn, Chem, Sac, 106I
lt/lr/ (/9rli), (3) Kom
etani, T, et, al, : J,
Chem, Soc, P@rkinTrans ヱ IIri7 (/rir/), (4) Naruta
, Y, at, al, : J, 5ynth,
Org, Chern, Japanj5L≠tr (
/ Rhiro).

However, all of these relate to the synthesis of racemates. There are no reports on the acquisition of optically active forms other than the synthesized racemic form, and at present no stereospecific synthesis of these optically active forms has been successful.

The racemic forms of these compounds are, for nanaomycin, a mixture of nanaomycin A and its enantiomer ≠-deoxycarafungic acid; for nanaomycin D and carafungin, these are the antipodes. It is a mixture of the two because of their physical relationship. On the other hand, since each compound has different properties as an antibiotic, it is desirable for pharmaceutical purposes to obtain it as an individual compound rather than a racemate, and if synthetic methods are an alternative to microbiological methods, these It is desirable to produce or obtain compounds as individual compounds rather than as racemates, but as is well known, it is not always easy to obtain individual compounds from racemates, that is, to resolve optical isomers. do not have.

SUMMARY OF THE INVENTION The present invention seeks to provide synthetic raw materials useful for stereospecifically synthesizing pyranonaphthoquinone compounds such as nanaomycin D1, nanaomycin A, and carafungin.

That is, the compound (1) according to the present invention, the following compound (I
) and the method for producing compound (m), the following compound (I)
and (Ph)5P=CHCOOR1 or (RIO)28
It is characterized by reacting with cH2coo R1.

(+) (II) (m) In each formula, R1-R7 represents one of the following -.

R1+ R6+ RT: -CH3* -C2H5 fusion~R5: -H, -OCH! l, -0C2H5 Effect In the present invention, compounds that already have the main part of the nanaomycin skeleton (1) are used as compounds to induce nanaomycins.
), but since compound (1) is a mixture of stereoisomers regarding the hydroxyl group at the 3-position of the pyranose ring, compound (Ph) 5P=CHCOO
Reaction with R1 or (RIO)2F(=O)CCOOR1 produces two compounds (II) and (m). Compounds (II) and (m) have skeletons that are closer to those of nanaomycin, and as is clear from their chemical structures, they cannot be used to separate each other. The separated compound (1) can be separated by a much easier method than the separation of optical isomers because it has sufficient differences in physicochemical properties.
Further reactions are carried out for each of the following compounds (I) and (III).Thus, nanaomycin D is obtained from compound (IF) and carafungin is obtained from compound (m) as optically pure substances. Obtainable.

Detailed Description of the Invention The target substances of the method of the present invention, pyranonaphthohydroquinone compounds (the above-mentioned compound (n) and compound (■)), are
It is produced by reacting the above compound (X) with (Ph)5P=CHCOOR1 or (R10)2M CH2COOR1.

Compound (1) and its synthesis Compound (1) can be produced by any purposeful method. Specifically, it can be synthesized, for example, by the following process.

In the above flowchart, compound (1) and compound (
2) are all known substances, and compound (1) can be synthesized, for example, by the method reported by Hauser et al. (Hauser @t, al, : J,
Am, Ch@m, Soa.

/It, /14.2 (/rirp), Hau
ser @t, a1. : 1b1d, -iot-
7oyr (see tr4c)). Also, compound (2)
Paula@n: Cham, Bar,...
110 (A), λ/λ7-141 (/ri77)
can be synthesized by the method described in or the method developed by the present inventors (see below for reference examples).
1) The latter is more practical in terms of synthetic yield).

The substituents R2 to R6 of these rust compounds are as defined above, but preferred in the present invention are R2=O
Me, R5~R5=H1R6, R7''HMe (
Me; methyl).

In the method of the above flowchart, first, compound (2)
, lithium tart-butoxide (11th1um
tart-butoxlda) to obtain compound (3). This compound was subjected to granulation, alkylation of the hydroxyl group (compound (4)),
Compound (D) can be obtained by hydrolysis with a stereoselective ketone compound (5)) and an acid (see Reference Example λ below for details).

Reaction conditions for compound (1) In the present invention, compound (I) and (Ph)3P = CHCOOR
1 or (R10)2PCH2COOR1 to form compound (1), the following compound (I) and compound (n[
) are as follows. In addition, (Ph
)5 P = CHCOORI or (RIO)2PC
R1 in H2COOR1 represents a C1-C2 alkyl group, all of which are known substances.

This reaction can usually be carried out in an inert solvent.

Preferably, the solvent that can be used is one that can at least partially dissolve at least one of the two reactants, and specific examples include toluene, benzene, xylene, and DMF.
SDMSO etc. can be exemplified. These solvents may contain some water, but it is more preferable that they contain no water. In addition, compound (I) is (RxO)gj,
When reacting with CH2COOR1, it is necessary to carry out the reaction in the presence of a base such as sodium hydride, butyllithium, etc.

Concentration of compound (I) at the start of the reaction and (Ph)5P=
Yes~koO%, (Ph)5P=CHCOORL or (
The amount of RIO)2(I P CH2C00R10 used is 1 mol or more, or 1 mol to μmol, per 1 mol of compound (I), and the dose is not critical. It is advantageous to use it in a ratio of 1 mole to 1 mole or more, preferably 1 mole to 1 mole.

The reaction temperature is also not critical and can generally be carried out within the freezing point to boiling point of the solvent used.

According to this reaction, compound (I) and (Ph)5P=CHCO
OR.

or (Rho)2P CH2COOR1, Compound (II) and Compound (III) are produced in a ratio of approximately /:l, but this reaction is completed in about 7 to 2 days under the above conditions. be able to.

Isolated compounds of product compound (n)i- and compound (m) (
f) and (Ph)5 P= CHCOORI or (RI
O)2 Any suitable means commonly used in the field of synthetic organic chemistry can be employed. Specifically, it can be easily carried out by silica gel chromatography, recrystallization, distillation, etc.

Usefulness of compound (II) and compound (III) Compound (II) or compound (III) obtained by the present invention
) can be used as a raw material for the stereospecific synthesis of optically active compounds having a pyranonaphthoquinone structure such as nanaomycin D1, nanaomycin A, and carafungin.

If compound (II) or compound (III) is used as a synthetic raw material, nanaomycin D1, nanaomycin A1, carafungin, etc., which could not be stereospecifically synthesized in the past, can be synthesized.
As mentioned above, it can be synthesized very easily in a stereospecific manner.

Specifically, for example, Nanaomycin D is the following compound (
II) Therefore, it can be synthesized using the following flowchart (see Reference Example J for details).

Furthermore, carafungin can be synthesized from Compound (III) below according to the following flow sheet (for details, see Reference Example Hiro).

Furthermore, Nanaomycin A1 can be synthesized by reducing Nanaomycin D with hydrogen.
It is clear from the above specific examples that it is useful as a raw material for the synthesis of various derivatives of carafungin.

Experimental Examples/Compound (Iff) Compound (1) ito,riW (0,!02 rn!
! 101) in toluene u, 13 vtl, PJP = CHC00Et J2A, j9(/
, ! /m mol, 3 times mol) was added. 10s”
After stirring for 30 hours at c, it was concentrated, treated with a silica gel column (r K1aae1g*140 J 1017, benzene/ethyl acetate = 7//1), and compound (1) was purified with the following compound (I).7. jg (yield 3
h) and compound Tsukuda) to, otsu (yield ratio/%) were obtained.

Compound (1) obtained in Tonoyo 5 The physicochemical properties of the following compound (I) and compound (m) were as follows.

L-(-1-)-rhamnose! rOg (o,, 27m
o1. /hydrate) (6) with methanol 2! 10% methanol solution of hydrochloric acid was added thereto, and the mixture was refluxed for n hours. After confirming the completion of the reaction with TLC,
The reaction system was neutralized with NaHco5, filtered through Celite, and concentrated under reduced pressure. Add this to 230 ru of acetone
After dissolving in t and filtering through "Celite J-Hiro!", it was concentrated under reduced pressure to obtain compound (7)! 0. Ji was obtained (yield 1oot
s or more). The TLC data is chloroform/methanol = 1 and Rf = 0. It was J'J.

A solution of the compound (3y, jp (o, 2 Jmol) in anhydrous pyridine 3!d was added with trichloromethyl chloroformate 3j, ritm (0, JJ!!lot, /, 1) under water cooling.
After the dropwise addition, the reaction system was returned to room temperature and stirred for 1 hour. After confirming the completion of the reaction by TLC, /2.0td(0,AA7rnol) was added to the reaction system.
To the mixture, cold water was added in an amount of 2 times the mole of chloroformic acid trichlorate per methyl methyl, and the mixture was directly concentrated. After concentration, toluene! od
It was azeotroped three times. The residue was treated with ethyl acetate and N
200 yl of a saturated aqueous solution of aHCO3 was added, and the compound (8) produced by the reaction was extracted into an ethyl acetate phase and separated. Furthermore, ethyl acetate 30011 was added to the aqueous phase,
The extraction/liquid separation operation was performed twice. The obtained ethyl acetate phase was washed with saturated brine, dehydrated with anhydrous sodium sulfate, filtered through cotton, and concentrated to obtain a white solid of compound (8)! Hiromu, 3I (yield over 100%) was obtained. The TLC data is benzene/z-tyl acetate=l/
At i, Rf = 0.4c/te.

A solution of compound (8) 3zrg (O, #jmol) in anhydrous pyridine (J7rml) was added with p-toluenesulfonyl chloride! under water cooling. Utah g (0,277rno1./,7
twice the mole) was added. After io minutes, the reaction system was returned to room temperature,
After another 10 minutes, the reaction system was placed in an oil bath at 60°C and reacted for 36 hours. After confirming the completion of the reaction by TLC, add ethanol/+, 31R1 (p
-) was added, and the reaction system was concentrated after stirring at room temperature for 30 minutes. After concentration, azeotropy was carried out three times with 30 vtl of toluene. Add ethyl acetate JOOrn 1% NaHCO3 saturated aqueous solution 200% to the concentrated residue.
rttl was added, the compound (9) produced by the reaction was extracted into the ethyl acetate phase, and 3 ooom of ethyl acetate was added to the aqueous phase.
1 was added to extract compound (9). The obtained organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The concentrated residue was subjected to silica gel chromatography (rKiaaelgIl AOJ
/3301, treated with benzene/ethyl acetate = 6A) to produce a colorless transparent syrup of compound (9)! ;, 3. (L
-(4)-rhamnose #) yield rob) was obtained in 3 steps. TLC data is benzene/ethyl acetate;
f=0.72.

Compound (9) 7o,t g (o, /ri Jmol)
seaweed! Sodium iodide, 23g (23g) previously dried under reduced pressure in thiacetonitrile aqueous solution 700111
7 mol, f times mol) and zinc powder 102 g (1,j
6 mol, twice the mole of Ir) was added, and the reaction system was purged with argon. Thereafter, the mixture was placed in an oil bath at 7°C and reacted for 36 hours under an argon stream. After confirming the completion of the reaction by TLC, 3 joytl of ethyl acetate was added to the reaction system, and the mixture was filtered through Celite. After filtration, the Celite was washed 5 times with 100 rtl of ethyl acetate. For R liquid and washing liquid! Add 3 rottl of sodium thiosulfate aqueous solution,
Extraction and liquid separation are carried out, and ethyl acetate is added to the aqueous phase.
ml was added and extracted and separated three times. The organic phase was dehydrated over anhydrous sodium sulfate and then concentrated under reduced pressure (below -°C). The concentrated residue was subjected to silica gel chromatography (rKl
eaelgel 60J /u00fi, carbon tetrachloride/
Separate and purify with ethyl acetate = 7/1B) to obtain compound a.
[Pale yellow syrup/yield <0.0%] was obtained. The TLC data was benzene/ethyl acetate=1, Rf=O, Coro.

Compound <11 o, Hiro1r7J (j, jlrmmol
) in anhydrous dichloromethane solution 2.7 d under water cooling, add molecular sieve 13 powder 1. oxg (o, 3 g for alcohol/m mol) and pyridinium chlorochromatone, tll = g (j, 77 m
(mol %J times mole) was boiled and allowed to react at the same temperature for 30 minutes. After confirming that the reaction has finished using TLCK,
The reaction system was diluted with ether 10N and directly subjected to silica gel chromatography (rKlaaslgal 60
J 12g, crudely purified with chloroform/ether = IA), and the fraction containing compound (2) (/, r, t~J!Jr
ttl) was concentrated by distillation at normal pressure (bath temperature near j'C) to obtain a yellow syrup of compound (2) O1≠/y (yield J't1). The TLC data were as follows: Benzene/ethyl acetate=V1 and Rf=0.72.

Anhydrous tart-butanol 0.73-Od (7,rij
mmol.

3.3 times mole relative to compound (2)) was added to anhydrous tetrahuman c17 run≦1#ml, and after replacing with argon,
The reaction system was cooled by 0"crtc, and Kn-butyllithium II, !Oml (72J mmol, compound (2
) was added dropwise. After the dropwise addition was completed, the mixture was stirred at this temperature for 10 minutes. Next, the mixture was cooled to -71 r°C, and compound (1) (dried under reduced pressure for 1.5 hours before the reaction was used) 0jOjJ,9 (2.4rmm
1.1 times the mole of olo compound (2)) was added and t
The mixture was stirred for S minutes. Furthermore, at −7r”C, compound (2)
(Before reaction, azeotroped 3 times with 0.Jrnl of anhydrous tetrahydrofuran) 0.3≠1zi (2, uOmmol)
Anhydrous tetrahydrofuran solution (4 μ0 tnl, μ times the amount of compound (2)) was added and kept at this temperature for is minutes. Thereafter, the reaction system was returned to room temperature and reacted for 3 hours. After confirming the completion of the reaction by TLC, the reaction system was diluted with 10-ethyl acetate, and further, under water cooling, a saturated ammonium chloride aqueous solution t, ra and water t,
rynt was added to extract and separate the reaction product. Sarak
Then, toml of ethyl acetate was added to the aqueous phase, and extraction and liquid separation were performed three times. The organic solvent phase was dehydrated with anhydrous sodium sulfate and then concentrated under reduced pressure. The concentrated residue was treated with silica gel chromatography (1Kissalgel 60 J/!All, hexane/acetone=''/1) to obtain compound (3).
) containing fractions (/j!R1~37m1) were collected and concentrated under reduced pressure to obtain a yellow solid o)tic yield of compound (3).
o 1) was obtained. TLC (7) data is hexane/
Acetone=V1 and Rf=17. J≠−1”, it was.

Compound (3) /, 10 f (J, 61 mmol
) in anhydrous acetone pmz, M+! 2SOX 1
．． 2 yd (/2.6 mmol.

3, Yuba mole) and 2CO31,7! ,9 (/ko,
A mmol.

3,! twice the mole) was added. After stirring for /j hours at tR) °C, Me2SO40,A ml (6,Jl mm
ol, /, 7 times the mole) and 2CO3r, 74c”9
(6.32 mmol, 1.7 times the mole) was added thereto, and the mixture was further stirred at Q°C for 72 hours.

The product was extracted and separated. Furthermore, 3 ethyl acetate was added to the aqueous phase.
The operation of adding o- and extraction/separation was performed twice. After washing the organic solvent phase with 30 rnl of saturated saline, it was washed with anhydrous sulfuric acid)
The mixture was dried over IJum and concentrated under reduced pressure to obtain compound (4), which was used in the next reaction. TLC data is hexane/
Acetone = V1 and R106Jλ.

Compound (4) was dissolved in methanol 33xlVc, and NaB
T.

#4C1!9 (44, Jl m mol a compound (
Add /j times the mole of 3) at room temperature, and! Shake for 5 minutes. After confirming the completion of the reaction by TLC, "Resin ca-s.

J (H" type) K was neutralized, filtered and concentrated. This was applied to a silica gel column (1" K15s*1g@140 J
! ;01.

The compound (
Needle-shaped crystals of 5) were obtained (yield of compound (3): U). The TLC data was pe2zene/acetene=4'/1 and Rf = 0,411.

Compound (5) ztt, o my (t, zu m m
ol) to 0. J-N Hydrochloric acid 2Q&d and acetic acid 4C,/yJ
Dissolves in and 7! It was left at ℃ for 2 hours. After confirming the completion of the reaction by TLCK, it was neutralized with NaHCO2 (solid) and a saturated aqueous solution of NaHCOs.
d twice). The organic solvent phase was washed with saturated brine, dehydrated with anhydrous sodium sulfate, and concentrated. The concentrated residue was transferred to a silica gel column (Kias@1g@l 40
J: IDI, benzene/acetone = v1) to obtain a yellow syrup of compound (I)≠76, λ■ (yield j, Jl). TLC data shows that benzene/acetone = V1) Rf=0.22.

Compound (II) 20) m9 (0,0!93 m
mol) in anhydrous acetonitrile Qul-, e
erie ammonium nitrats (CA
N) 41.3 m? (0,II mmol, 4 times the mole) dissolved in water Q26rnlK was added. After holding for 1S min at room temperature, ethyl acetate Jmj and water 1111
1 was added to separate the layers, and the reaction product was further extracted twice with ethyl acetate 2d. The organic solvent phase was washed with saturated brine, dehydrated with anhydrous sodium sulfate, and concentrated. The concentrated residue was transferred to a silica gel column (Kies@1galtOJ
I) #, benzene/ethyl acetate = 3/1) to obtain compound α])lz11n9 (yield: 2).

TLC data shows R with benzene/ethyl acetate = 3/1.
f=0,2/.

Compound (11)/ri, o my (o, ogop mm
ot) was dissolved in anhydrous CH2Cl2o, Tata wLIVC. While stirring under water cooling, AlCl31POIQ
(1, u2 mmol, Jjj times the mole) was added. Thereafter, the mixture was stirred at room temperature for 30 minutes. After confirming the completion of the reaction by TLC, 117% of water was added under ice cooling. Add r-,
The reaction product was extracted r times with chloroform/5IR1. The organic solvent phase was washed with 3.0 ml of saturated brine, dehydrated with anhydrous sodium sulfate, and concentrated. The concentrated residue was subjected to pre-varatip TLC (Q21m plate, width: 10cm, λ
After developing with dichloromene/chloroform = 5/1, the fraction corresponding to nanaomycin D was extracted with ethyl acetate and concentrated to obtain nanaomycin DI 7.2119 (yield: high). TLC data showed benzene/ethyl acetate=571 and Rf=<7.4 L/.

Compound (Iff) Core 1 ff1p (0,tripmm
ol) was dissolved in anhydrous acetonitrile. To this, CAM7471+19 (1,32mmo1.-
A solution of 2 times the mole) dissolved in 3.0 moles of water was added. After holding for 1S min at room temperature.

Add ethyl acetate 111117 and water totd to separate the layers, and then add ethyl acetate lOI! The reaction product was extracted three times at step 7.

The organic solvent phase was washed with 1 OIR of saturated brine, dehydrated with anhydrous sodium sulfate, and concentrated. The concentrated residue was passed through a silica gel column (Ki@s*1gel AD J r, 01
, purified with benzene/ethyl acetate='/1),
Compound 1 was obtained in 220 cm (yield: tt). TLC data.

Benzene/ethyl acetate=5/1 and Rf=0.34<.

Compound (L322.riq (0,06lA m mol
) was dissolved in anhydrous CH2C12/111w1 and diluted with AlCl32JOm? under water cooling. (/, 72m mal,
After adding 27.1 times mol), the mixture was stirred at room temperature for 30 minutes. Under ice-cooling, water/ml and 5 μm/ml of CHCl were added to separate the layers, and the mixture was further extracted 5 times with 2 portions of CBCl3.

The organic solvent phase was washed with saturated brine, dehydrated with anhydrous sodium sulfate, and concentrated. Prepare the concentrated residue7
Developed with 'TLC (benzene/ethyl acetate='/1) and demethylated the methoxy group of the compound 20. It was obtained for free (yield: 71). The TLC data was benzene/ethyl acetate=3/1 and Rf==ll:ljj.

This demethyl form it, rm9 (o, oe76 mmo
1) was dissolved in 0.3 K of anhydrous benzene and cooled on ice.

This is K.

Concentrated sulfuric acid q-ton was added. After stirring for m minutes at room temperature,
Immediately cool on ice and add 0.0% ethyl acetate. After dilution with Jul.

Furthermore, water 0. ! - was added, and after stirring, the mixture was separated for 1 minute. moreover,
The reaction product was extracted 7 times with 0.2 dK ethyl acetate. The organic solvent phase was dissolved in a saturated aqueous solution of Na)I C03 0.3
After washing with rd (aqueous phase p) I=2], saturated saline solution 0
, Jul. After dehydration over anhydrous sodium sulfate, the mixture was concentrated under reduced pressure. The residue was diluted with toluene. Dissolved in ri-.

Stirred for 7 hours with ioz"c. After concentration, preparatip T
L C (1 piece of 0.2i parrot plate, dichloromemene/
Calafungin 13 was treated with chloroform = 3/1).
, lda (yield octopus, 04) was obtained. TLC data is
Benzene/ethyl acetate=3/L and Rf=O, ≠l.

Nanaomycin D was synthesized by the following process. Nanaomycin D Nanaomycin A Nanaomycin D14.0 was dissolved in ethanol J, 0w15, platinum black rII9 was added, and the reaction system was shaken for 1 hour in a hydrogen atmosphere of 3 atm. Last night. Thereafter, one reaction system was filtered and concentrated under reduced pressure. Treat the concentrated residue with preparative TLC (benzene/acetone = 3/2) 1. As a result, nanaomycin A/≠, tda was obtained.

By reducing carafungin in the same manner as nanaomycin D, l-deoxycarafungin acid was obtained. The physical and chemical characteristics of the reference-related substances are as follows.

Compound (9) Melting point, t~lO1℃; [α] +236(C
1,01CHC13); I R(KBr)Ir1
6, /7riλ, l17ta (cll-”)
1H-NMR (TOMHz% CDCl3)
δ/, 31 (JH, d, Me.

J51M@=A Hz), 2.4# (3B,
m, TsMe), 3,4cO(jH,s,
OMe), J, Ir6 (JH, dq, H-j,
JII, 5 = RI, 0IIZ), $, 2J -II
, 72 (3B, m, H-J, J and da), μ
, Ri J (JH, s, H-1), Otsu 440 (2H,
d, Ttx.

JAB "riHz), 7.1r7 (JH, d, Ts)
;Molecular weight (molecular formula) 3! r, 3t (c15Yhso
ss ); Elemental analysis value (regret) (calculated value) C=!
0.02 (!0,27), H=, 0ri(z,
ot compound part TLC (benzene/acetic acid x f = 2//) R
f = 0.24; Boiling point (7 mmHg) - 0°C; [α):
-2ot0(c i, o, CH3Cl3);
1H-NMR (TaOMHz, CDCl!+D20)
δ/, 2 (3B, d, Mll, J5.Me =
6. ! Hz), 3. μta (3H2s, OMe
), 3.7bu (JH2 wide s, H-2), u, 30
(JH, dq, Ht, JII, 5=/jHz)
, 4A, 71 (JH, s.

H-/), J-, ri0 (2H,s, H-J and 4
'eJ3. II:10)Ih); Molecular weight (molecular formula)
/ Cup, /7 (07H120B); Elemental analysis value (regret)
(Calculated value) C= kg, θr(jr, s2), H
zr, it (r, 3ri) Compound (2) Boiling point ('ll31Hz) '” ℃; (α)r-
'! '(C/, o.

CHCl5); 1H-NMR (Ta01Mz
, CD013) δ i, a.

('L da Mll J5.Me =71 Hz)
, J, jr (J H, @.

OMs), lljri (JH, ddq, H-j, J5.
5=2. jl! .

JH,5=l,jHx),u,73(JH,s
, H-/ ), bu, Ot(/ H, dd, H-3,
J5,4 = 10.1Hz), t, i(i's.

aa, H-4'): Molecular weight (molecular formula) tax,
tr (C7) 11003); Elemental analysis value (correspondence) (calculated value) C= jr, 73 (jri,/!), H=
4. Ri1(7,0ri) Compound (3) Melting point/23-12! "C;[Eα禮-3014" (C
1,0.

CHCl3)', I R(KBr) IA4c7
．． #J/, 1610°1!11 (cll-1);
UV (Moon)λ(g) Jul (817-
00), At! (22100), 2A1 (2#
00), 321 (2100), 329 (321
0), 3ft (#4AO), 4c3/nm
(ru20); “E-NMR (TaOMEz, CD
C1B) δ/, 73 (JH, d, Me-/,
Jl, M, = 6. jHz), jjp (JH,
s, OMa-j ) , u, 0ta (3B, s, OMa
-ta), j, Or (/H,s, H-J),
j, ≠'('H# qe E-'), 7.02 Oyo Ur, 07 (each/H, dd, ) i-A and r, J
= r and /, jHz), 7.4to (/H, t,
H-7, J = tHz), 2.20 and 12.3
2 (1 turtle a, OH-! and IQ, vice v
*ram) ; Molecular weight (molecular formula) 3017. JO(
C16H160G); Elemental analysis value (arrogant) (calculated value)
c=43.4Cl (63,l!), H=j,
! (1,30) Compound (4) Yellow oil; ((ri”-/74” (CI, 0. CH
Cl3); IR(CBCl3)/70i,
Jl03,/! 71. lr&? , 14Atn(z-
1) ; ty V (MeOH) a (a) 22
t (2azoo), 262 (26100), 2
9! (3r60), 30! (4AOJO), 3
Ko0 (3#0), 37ta (J/ri0),
31! Hm (Infl.

Review! 0 ); 1H-NMR(ri(7MHz, CD0
1B) δ/jri(m, H-J),! ,≠/ (/L
q, H-/), 7.02 and 7, r(each/
H, d, H-4 and t, J ==JrHz), 7,
Hirot (/)i, t, H-7) ; Molecular weight (molecular formula) % Formula % (Pale yellow crystal; Melting point tyt-177, z℃; Cα]2'
-Tough.

(C/, (7, CBCl3); I R(K
Br)/jri6, Jl7ko, 1100, /4A62
．． /17141.138%126&(ffi)
;UV(MeOH,) λ (g) 2J! (!
31r00), 293 (!620), 307
(7110), 32λ (4000), Jl7 nm
(4A7uO); 1H-NMR (uooMHz,
CDCl3 ) δ/j7 (3H.

d e M'-' p Jl, Me =7. (7Hl
), 3.21 (/H,d, 0R9-1', J
q, OHg4L, OHz), Jl2 (J)I,
s, OMs-J), s, rco, u, oi and a,
op (each JH, s, OM・×3).

1, rij (/H, d, H-j, J5.* = 2.o
H2) , r, or (/H, dd, H-u)
% t0 cups (tH, q, H-/), 631 and 7.70 (each tL (1, H-t and r, J=tHz
), 7.1-0 (/H, t, H-7) ; Molecular weight (molecular formula) % formula %) ( (molecular formula) 32o, za (C17of!o o,, )
; Elemental analysis value (1) (calculated value) C= AJ, 41
(t3.74c), E = 6. # (6,2) compound ell) Yellow needle-like crystals; melting point 2t4A-ztt ”c (decomposition);
[α]24-41” (CO,!, CHC1B);
IR(KBr)~/716°~1Ajr,/!
T! (cll-1) ; UV (MeOH) A
(#) Jl2 (xtyoo), xis (t2
poo), 26! (Infl,,ytoo),3r
t (3390), 4AO3nm (3160);
"H-NMR (9ONEz, CDCl5) δ
/,! 6 (J H2de Ms-'p'l2Me
=4. 'Hz), Jjj (/I(,d, )
! -//.

""=1"="Hzy '3.11=OHz
),! , rij (la, aa.

H-/l', J5. H'=! , OHz) ,
Il, 01 (JH, a, OMa), 44.42 (
/H, dd, H-J, J34=JH2), r, Or (
/H.

q, H-/ ),! , 27 (/H, d, H-Hiro),
7.3-Otsuri (3H, m, H-Otsu, 7 Ourabi r); Molecular weight (molecular formula) % Formula % (orange oil of compound α; Ca] Nee m6 (CD, r, CBCl3
);IR(CHCl3) 1730, /AH
, tbuco J, 1190, /4471, 8LrO(
cIM-1) ; UV (MeOH)λ(a) J
//(22000), 2447 (13000)
, 267 (Inf 1.

ttroo), 33 (21!10), 31! (
Infl,, 3670).

3t nm (3!20); ”H-NMR (4
AOOMHz, CDCl! 1) δ 1,21 (J
Me of R, t, It, J m 7. )
, /, 44ri (JH, d, Me −/, Jl, M
,=6. ! Hz), ko)7 (/H.

dd, H-//, Jl, ll=ri, OI(z
# Jll, u' == # Hz).

Ko, 2! (/IH, dd, H-//', J3.u'=
J, OHz), 33! (Iw, at, B-J,
, r3,4=ri, □Hz), u, ot(sH.

s, OM・), gu, 12 (/H, d, OB-≠#
JK, OH= /, OHE ), a, iyt and u
, 2oa (CH2 of each/H, q, Et), 4! j
/ (/H, ddd, H-44, Jl, 4=2.0H
z), Hiro, tri(II(, dq, H-/), 7.3
/ and 7,7J (each /H, d,) I-j and r,
J = rHz), 7.67 (/)I.

t, H-7); Molecular weight (molecular formula) 360.36 (C
19H2007); Elemental analysis value (regret) (calculated value) C=
62. rit(63,33), H=J,tco
(!,!ri) Nanaomycin D Red; Melting point 17/-/73℃; [α: l",,'-/
13°(C0,μCHCl3); I R(KB
r ) ~/771, /7jj, /7JO.

1A61, #J7, #JP, 1 nail 2 (am-
”) ; UV (MeOH)
0200 ), 31! (Infl,, 2190
), 4t27nm (uu20); 1H-NMR
(4AOOMHz, CDCl3) δ1,! 7 (J
H, d, Ms-/, Jl, M, = 7. OBz)
, ko, 71(/l'1. d, H-/)p J
ll, 11'= ItHz, Jl5, 11
= OHz), ko, ri7 (/)I, dd,
H-//', J5. H'=! ,OHz),'A,6
(/H, dd, H-J, δ5.z=3.0Hz
),z,ori(/)I.

q,)! -/), j, mu (In, a, H-da), 7. J
/ and Ku7/ (each /H, dd, IH-4 and 'p
J=1.0 and ko, 0N(z), ot AI (/H, t
, H-7, J = Jr, OHz), 11, r4A
(/H, I, OH-ta); Molecular weight (molecular formula)%
Formula %)) Absorption spectrum, 1E-NMR (4AOOMHz
, CDC13) spectra were completely consistent with the literature values for carangin.

Nanaomycin A Orange needle-like crystals; Melting point/7P-III 'C;[:α]"
-20,t''(CI,4',CHCl5); U
V(MeOH)λ(t)2t.

(1110), J7# (/2200), 4t2
J (41041-0); “H-NMR (WOMH
z, CDCl3) a t, jr (jH, d.

M@, Jl, M, = 7 Hz), Ko, JJ (/
H,ddd, H-IJ4,11'=/riHz, δ5
．． II=IOHz, J14=JHz), 2.72
(KH, d, CH2-/), J == 4. tH
z), 2.17 (/H,dd, H-4'
, δ3. II'=J Hz), 44,344 (
/H, m.

Ti-J), j, 04A (/H, dq, H-/
), 7.2-7.7 (JR, m, H-6,7 and r
), r, r (/n, m'-outside.

Coon ), /2. OJ (/H,I, 0H-5
F ); Molecular weight (molecular formula) 3θ', &21" (C
1gH411O6); Elemental analysis value (calculated value) C
= 43. ! 0 (t!, !7), Hall, 70
(Fjj) Goodeoxycara 7-angic acid [(1]: +20.6 (CO, II, CHCl3)
; So (Q and others kl f f off 4 Fufu people.

Claims (2)

[Claims] (1) The following compound (I) and (Ph)_3P=CHC
A method for producing compound (II) and compound (III), characterized by reacting OOR_1 or ▲Mathematical formula, chemical formula, table, etc.▼. ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(III) In each of the above formulas, R_1 to R_7 are as follows. Indicate either. R_1, R_6, R_7: -CH_3, -C_2H_5R_2~R_5: -H, -OCH_3,
-OC_2H_5 (2) (Ph)_3P=CHCOOR_1 is converted into a compound (
The manufacturing method according to claim 1, wherein R_1 to R_7 are as follows. R_1:-C_2H_5, R_2:-OCH_3, R_3~R_5:-H, R_6~R_7:-CH_3