JPS6078962A - Production of prostaglandin d1 - Google Patents

Abstract

PURPOSE:To obtain a PGD1 useful as a medicine easily in high yield, by protecting the hydroxyl group at the 9-position of a specific PGF1alpha with a group capable of forming an acetal bond, and subjecting the protected PGF1alpha to the selective removal of the protecting groups, oxidation, removal of the protecting group and hydrolytic reaction. CONSTITUTION:The hydroxyl group at the 9-position in a PG(prostaglandin)F1alpha of formula I [R<11> is 1-10C alkyl or tri(1-7C) hydrocarbon silyl; R<2> and R<3> are H, substituted or unsubstituted 1-10C alkyl, etc.; R<31> is tri(1-7C) hydrocarbon silyl; R<41> is a group capable of forming an acetal bond with the oxygen atom of the hydroxyl group] is protected with the group capable of forming the acetal bond with the oxygen atom of the hydroxyl group at the 9-position thereof to give a PGF1alpha, which is then subjected to selective removal of the protecting groups, oxidation and hydrolytic reaction to afford the aimed PGD1 of formula II(R<1> is H or 1-10C alkyl; R<4> and R<5> are H, etc.). EFFECT:Separation of isomers of cubic configuration is not necessary.

Description

[Detailed description of the invention] The present invention provides prostaglan γ-in 1] I (controlling the above) aD
(abbreviated as 1). Roughly revised 9
4it, the 15th position is protected with a group that forms a hydroxyl L (M group) rutal bond, and the 11th position is protected by a silyl group e.
Involved in a new J↓l manufacturing method that induces G D + type products.

P G Dr type 1 among the primary P G JiY [E +, PGF + α, type 1]
PGE belongs to the same group, and has biologically active platelet aggregation inhibiting activity.
It is the second most powerful compound with different biological activities, but even more biological activities are not well known. Recently, a compound having antiplatelet and antiasthmatic effects has been found in PGD+ analogs (see Erik, William, and Colin Tow, special issue 1987-102,877).

Conventionally, there are 14 methods for cleaving PGD+ species, namely, 1) a method of biosynthesis from (l) all-cis-8,11,14-lithorienoic acid (CJ, Si
l+S, Biocbemistry, 11.22
71 (1972)).

(2) Method for producing 1q by selective participation of water lI! group at position 9.11 of P G F +α. (G, L, Bu++d
yS, J.

MC! d, Cltcm, 20. 7H (1983
>Reference).

+31 The carbonyl group at position 11 is 1,3-didio)noL
7J payment obtained from compounds protected with tar groups (A, T.

1-1e1-1e S, F! L11allOdW
II 11itt,, 23. 5 (31 (1982)
reference).

(4) 9.11.1! A method of deriving Lj from P G F + α derivatives maintained by different cylindrical molecules at position i
l-, W.

Tart S, J, Chem, Com1,156
(197j)) is known.

However, in these methods, the polyunsaturated fatty acids that are the raw materials are not only difficult to handle manually, but also the biosynthesis involves the biosynthesis of 1:P.
G E + , P G F '+α are produced as by-products, and P G
1) There are many difficulties in separating + from these 1- karma-like Buddha tastes. In chemical synthesis υ of (2), it is necessary to delicately control the reaction to selectively oxidize only the 11th position of the two free hydroxyl acids at the 9.11th position. Moreover, the yield is low, and there is not necessarily a swirl layer within the leaves. In method (3), the carbonyl at position 11 is protected with 1,3-dithia aretal and the I mesidium is used, so the steric structure at position 12 is created by PG skeleton synthesis 1)
! 1 does not have 1' for control, and the product is a compound with an unnatural isomer, and there are difficulties in separating these. In 7J rL of (4), positions 9 and 11 are protected with the same protecting group different from the silyl protecting group at position 15, only position 11 is distinguished from position 9, and -C selective deprotection ρ etc. are different. Protected with the same protecting group, distinguishing only the 11th position from the 9th position, 10TU
Alternatively, 11) is a method in which 2 groups and 15 groups are 1-, which requires delicate reaction control and is complicated in the process of converting the protecting group at position 11 twice. , in an industrially satisfying manner.

The Ministry of the Invention and others have focused on this point and have developed an advantageous chemical synthesis method for buto-1 staglandin D1.
As a result of the research, l) G-skeleton synthesis U + Invention We skillfully utilized the hydroxyl protecting groups used to protect the 6 and 11 positions with a group that forms an alletal bond between the 9th and 15th positions and the oxygen atom of the hydroxyl group. From PGF + α species protected with silyl group, 11
We decided to convert only the position with a predetermined functional group.
We succeeded in obtaining the + class and arrived at the present invention.

That is, in the following formula (1), R11 is a C1-Coo alkyl group or 1-Coo (C
I-07) represents a hydrocarbon silyl group, R2 and R3 are the same or different hydrogen atoms, substituted or non-directly substituted 01
~C10 alkyl group or substituted or unsubstituted 5)~
Represents a 6-membered cycloalkyl group, 1 (31 is I.S(
(,+~Cy) represents a hydrocarbon lucilyl group, and "(41
is λ that forms an azetal bond with the oxygen atom of the hydroxyl group.
(Represents.

bu [1 staglandin 1-1 αP:i
The water M group at the 9th position of ol is j
It is protected by a method that forms an IL-tar bond, and the following formula (2) is formed, in which R", R", and I are 3,1 (the subtraction is the same as above, and 1<51 is the same as or different from 1<41). Hydroxic acid 150)
Oxygen 15: Represents a group that forms an allelyl bond with Miko.

Prostaglantin supra1α fue toxin expressed as 1-
1) This is selectively deprotected, then oxidized, and then subjected to deprotection and/or hydrolysis reaction as necessary.
The following formula (3) in which R2 and R3 are the same as defined above, R1 is a hydrogen atom, and C
It represents an alkyl group of 1 to Coo or a 1-li(C+ to C7) hydrocarbon silyl group, and R4 and R5 are the same or different and represent a group that forms an azetal bond with a hydrogen atom or an oxygen atom of a hydroxyl group.

This is a method for producing prostablandin D+ expressed by:

The prostablandin F+ α group represented by the above formula (1) used in the method of the present invention is obtained by a previously captured method (see Japanese Patent Application No. 7-163082). -99462
(see @) can be easily and easily cooked with a skewer with high yield! l! It is possible to read.

In the above formula (1), RI+ represents an alkyl group of C1 to CIO or a hydrocarbon-silyl group of 01 to CIO. Examples of the alkyl group of 01 to CIO include methyl, ' :t al, 11-bumepyr, 1so
-zo[1-biru, 11-butyl, 5ec-butyl, L
ert-butyl, 11-pendel, rhohexyl, rhohepdyl, ++-4 tatyl.

Linear or branched ones such as 0-nonyl and ++-q-syl can be mentioned. Nakadeshi methyl group and (2) thyl group are preferred. Examples of the (C+~Cy>hydrocarbon-silyl group) include trimedelsilyl, 1-liablesilyl,
1-(C+-C4
)Alkylsilyl also includes a Schiffonyl(C+-C4)al4nylsilyl group or a 1-ribenzylsilyl group, such as a diphenolsilyl group.

! <2. R3 is the same or different, water-based atom or substituted JibL,, < t, non-replaceable 01~(/
Examples of the 1-l group include methyl, 1-del11-nol-11-pyl.

730-propyl, l)-butyl, topemble, former l\
-1-Syl, 2-methyl-1-hexyl, 2-mebru-2-hexyl, 11-hebutyl, n-A cube, and other iO-regular or branched compounds are mentioned. unsubstituted 5.
Examples of the -6-membered cycloalkyl group include a cyclopentyl group and a cyclohexyl group. Substituents for such unsubstituted 01-Coo alkyl groups and unsubstituted 5-G membered cycloalkyl groups include, for example, methyl, ethyl,
Preferred examples include phenoxy, methyl, trifluoromethylphenoxy, and the like. In particular, R2 and -C are methyl.

Methyl, 11-pentyl, 1, optionally substituted with phenoxy or 1-lifluoromethylphenoxy group
1-hexyl, 2-methyl-1-hexyl, cyclopentyl group or cyclohexyl J,4 is preferred, even n
-Pentyl, 11-hexyl, 2-methyl-1-hexyl, cyclopentyl and cyclohexyl are preferred. R3
and °C is preferably a hydrogen atom or a methyl group, especially water;
An h atom is preferred.

R31, 1, (to IC+/C7) represents a hydrocarbon-silyl group, and is also 1-tibutyldimethylsilyl M.

Triethylsilyl group is preferred. R'' represents a group that forms an acetal bond with the oxygen atom of the hydroxyl group, such as methyl-oxymethyl, 1-eth4-di-1-methyl, 2-methyl-
Kishi 2-B L1 Hill, 2-Sat 1 Hexie 2P U Building,
Methyl.

Benzyl 71A dimethyl, 2-tetouji1ζ11binolne2-j-1~ugido1-1-nonyl, 6.6-
A 4-4-yl group, etc., is added to dimethyl-3-'A-1ni-2-A4-di-Schiff-1' (3,1°O). 1<41, inter alia, didropyranyl group, 1
-I+-=1-side del group, 2-me1-4cy2-propyl group is preferred.

The PGs that appear in the above formulas (1) to (3) 0 for the present invention/J payment are 8th, 9th, 11th, 12th, and 11th.
1st place.

Various stereoisomers exist in order to contain the asymmetric carbon ABI molecules, but in the method of the present invention, these enantiomers, optical isomers, and their -ξrei
5. It includes a mixture of

The method of the present invention is based on the above equation (1).
The process starts by protecting the hydroxyl group at the 9-position of the 1α group with a group that forms an aretal bond on the hydroxyl group. As a protecting agent, 2-3-dihydro-11-picine, - [
Pluvinyl 1-fur, 1-alvinyl 1-fluorene acetal 2, etc. are used. These protective agents are made from prostaglandin F! It is used in an amount of 1 to 20 equivalents, preferably 1 to 5 equivalents, relative to the α group. As reaction aids, pyridine balatoluene sulfone 5t=(ppTS), camphu 7 sulfonic acid, etc. are used at a concentration of 0.1 to 100 relative to the raw material prostaglandesone F+α.
It is preferable to use 1 to 30% by weight. The reaction can also be carried out in anhydrous ethers such as ethyl needle, tetrahydromefuran, di-7-nan, etc., or anhydrous chlorinated hydrocarbons, such as methyl dichloride, LTI form, dichloroethane, and the like. The reaction temperature is -10°C to 60°C or more preferably 0°C to 30°C.
The end point of the reaction can be determined by observing the disappearance of the raw materials using thin-layer magnetography or the like. Thus, the reaction solution was
- The product is protected by the 11th-position gasylyl group represented by the above formula (2), and the 9th and 15th positions form an aretal bond with the hydroxyl group oxygen group. PGF+α group-protected group is obtained. Next, silylated II at position 11 of this compound is selectively deprotected. This is tetra-11-butylammonium fluoride, hydrogen fluoride-hyridine.

In particular, by using Detler's 11-butylnylnorolide, 100R4' (wherein R'', R2, R3, R'', R'' are the same as above). The 9th and 15th positions represented by ) are protected.1) GF
I can easily read class Iα. This product can be prepared by a method known per se ([,13,Nil+iqawa3
1) tostagrandi+to 9, 109
(1975)), for example, the hydroxyl group at position 11 is oxidized with a chromic acid-based oxidizing agent such as rucumic acid pyridium 11, and CR is added as necessary.
" , R" protection J7. t may be removed. For the removal, for example, a mixture of intoxication-water-tetyl-hydrofuran (3
:1:1 to 3:2:2) at room temperature. 1! (E, J,
Corcy et al., J., Amar, CIoa
m.

Soc, 24, 6190 (1972)).

Furthermore, if necessary, the ester I (R'l) at the 1st position may be hydrolyzed. Such hydrolysis, for example F type 1)
G can be an alkaline aqueous solution, F type 1).

Thus, l- expressed by the above formula (3)
'GD1 class can be easily obtained at a high yield.

The characteristics of the method of the present invention are as follows. 'TJ, by making full use of the differences in the protection states of the hydroxyl groups at positions 9, 11, and 15 that occurred in the starting Lξ material (1), -C, and converting the protecting groups as in the conventional method. This is a method in which the intermediate represented by the above formula (4) is introduced instead, and this is asked of the PGD1 group. This method is much better than the conventional method.
However, there is a method that can provide P G Drs without stereoisomer separation of 4M m. The method of the present invention will be explained in more detail below with reference to Examples.

Example 1゜1 (103#I!J) was placed in a 10me eggplant flask and imQ dlyCtL CUz was added. Cool in a water bath, add 33 mg of 2,3-dihi I-ropyran,
Subsequently, 14 mg of l)I)TS was added and stirred at 0°C for 10 minutes. After diluting the reaction solution with 5 mQ of methylene chloride, saturated sodium chloride was extracted. (2X 10++ie) containing 41 gels, anhydrous MilW 1~lium (2) was dried. After concentration under reduced pressure, it was applied to a silica glue gel (12 g of silica gel made by M0rCk); 1111] (yield 94%) (!1k.

IR (CI-IC Mugi 3): 1730cm-111
NMR (CDCJla, 90~I11Z, 1l
iln+) δ:0.007(S, 6.Si'
Cl-13X 2 ), 0.7-1.0 (12,
Si C(CH3) 3 and C13),
1.1-2.5 (m, 3G, CH2X17), 4.5
- 4.8 (m.

2.0CI-10X2), 5.40 (Il, 2.vi
++y1>TLC: I<f: 0.54 (Et
OAc-1+exa+, c=1:4) Optical rotation: [α] = 15.9'(G003G5゜MeOl-1> Example 2 0.1
- of dry Cl-12cJ12 was added. Cool in a water bath;
4. Add 7■ of 2,3-dihydrobilane, and continue with U.
P
-1-30.2 mg was added and stirred for 2 hours at 30'CF. Additionally, 4.7 mg of 2,3-dihydrobyran, l)
t]T Sq, 2 mg was added, and the mixture was stirred for 1 hour. The reaction solution was diluted with 5 d of methylene chloride, 10 d of saturated 1N water was added, and the mixture was thoroughly shaken. The layer on the right is the layer. After fractionating the aqueous layer, dry it with sodium. After condensation under reduced pressure, it was subjected to silica gel column chromatography.
Kne 1 Silica gel 1,77: Vinegar - Boo: Hekirin -
1:10), -1 product was obtained in 29~ (yield 97%).

The spectral data were the same as in Example 1.

10m1! (1) 7. 75s'-11: 2 to 10
3.5#lj/Tori-1-I11 Dissolve in 1e, 1 After that, +1-[3u a NF (IM/ T I-I
Add 1.58 ml of F) and bring to room temperature (23℃> (
・Add ethyl 5Id and shake well. 41 Separate the organic layer and aqueous layer. Extract the aqueous layer with ethyl acetate (5d
×2), right t! One layer was combined and dried with anhydrous Putrium C sulfate. After concentration, it was subjected to silica gel column column chroma 1-graphy. M OI'Ck silica gel 1
07; Acetyl acetate: 11-hexane = 1:4), 71.7 mg (yield 84%) of -5- as a product 1-1k
.

IR (C1-I C113): 3620-328
0.1730cm-'TOINMR(CDCM3
, 9(IMI-12, 1)l)m) δ: 0.88
(t, 3. 4.51-12, Cl-13>
, 1.1-2.5 (m, 37.CH2X17.cl
-1x 2. alld 0tl), 3.3-4.5(
+i, 10,0CI-h, Cl-10X3゜alld
CH20X2), 4.5-4.8(m, 2.0C
I-10x2>, 5.45 (Drama 1.2, Vil
yl) Thin layer chromatography: Rr: 0. ri4 (L L OACIIC!X
allO=1:4) Optical rotation: [α] - [α] = +0.65° (CO, 58
8, Me Ol-1) Example 4 29.24 of 6 was placed in a 5 m test tube and -1-l-l F
Dissolved in O,5me, then n-Bu a' NF
(I tvl/-1l- for I) 0.45 mR 1''
11, air temperature 21℃, Ptvl 4: 110)
The mixture was stirred for 4111 minutes. After diluting with Tl1F2d, saturated water was added and the mixture was shaken well. rll acid■
Add Chill 5rnQ and shake well. On the right, separate the U and water layers.

The aqueous layer was extracted with yl acid (
). After concentration, Merck silica gel 1.7 was subjected to silica gel column 1. ; Ibi, 01 acid ■ Del: 11
-Hekylin'l: 2), 20 mg of product 7
(yield 83%) 1'7.

The properties of this item are: Example 3, b-do Ii+II;
There was C.

Example 5 Th? 0 10m! Take 5.1 #I9 in a l eggplant flask and at? Prepared IC with l-on 3d. Under argon flow,
At -30°C, 55.4 m (l) of Jones reagent was added dropwise using a microsyringe. After stirring at -30°C for 50 minutes, 3 m of a saturated aqueous 1-lium bicarbonate solution was added, and
Shita. After the aqueous layer turns green, 10% ethyl m-acid,
10 mQ of a saturated carbonated aqueous]-thorium aqueous solution was added, and the mixture was shaken thoroughly. Combine the right machine layer, 7! lj water 11il
Mnorium C was dried. After concentration under reduced pressure, it was subjected to graphy on a silica gel column Chroma 1 (7 g of Merck silica gel; acetic acid: hegisan (1:2)), and 64. IIyJ (yield 99%) was obtained.

IR(C1-IC,Q3): 173! Icm-'
:1-INMR<CDCILs, 90Ml-1z
, DI] III) δ: 0.88 (t, a, J
= (1,0+-12,CH3), 1.1-2. '
l(m, 3G, CI-+2 x17 a++d Cll
X2).

3.3-4.8 (m, N, 0C1h, Cl-10x
2. CI+2 0X 2, acid ocl-fax
2), 5.3-5.6(m, 2,' vin
yl ) -rLC: Rf : 0.33 ([t OAC-1
+cxa++a=i:2) Optical rotation: [α]=0. G3° (CO,7!i7!i
.

1yleOH > 11.7 in a 5 mQ test tube. [inf, 7' t
It was dissolved in I-ne 0,6-. ) Under argon flow, -3
Jones reagent was added dropwise with a syringe at 0°C. -30
The mixture was stirred at 4° C., diluted with 1 d of ethyl acetate, added with a saturated aqueous solution of sodium bicarbonate, and stirred vigorously.

After the aqueous layer turns green, add 10 mQ of saturated ethyl acetate and 10 mQ of saturated sodium bicarbonate, and stir vigorously.
. After separating the aqueous layer, the aqueous layer was extracted with acetic acid (2×10 d). The organic layers were combined and dried over anhydrous notrium sulfate. Decompression deep 11? i F2, subjected to silica gel column chromatography McCrck O,
9; Edge resistance: l\ki→non-1:2); 11 mg (yield 95%) of the product υ-; the properties of this product were the same as in Example 5.

Example 7 TI9ol-1c+ 8 (55,2me) was converted into 7d CLl 3COOl-
l' l-120-dissolved in THF (3:1:1),
Stirred at 45°C for 10.711'i. Concentrate on a rotary evaporator and azeotrope with toluene (3 times). The concentrated solution was directly subjected to Silino J Glucolumn chromatography (M
erck silica gel 5g; vinegar edge: to: 1-4 non-1
:1), and the product was P GD + methyl Nissal 28.78+y (yield 76%) 111k.

lR(C1-1cJ13): 3720-324
0. N30cm"'11NMR (CDCS3.90M
IIz, 111111) δ: 0.89 (t,
3. J = 6.4Hz, CH3), 1.1-
2.1 (m, 21.CH2x9.cl-1, and
01lx2> , 2.32 (I, 2.'J= 7
．． 0LIZ, Cl-12C00G), 2.44
(d, 2. J-2,6112, C112C=O)
, 2.79 (dd, 1, J=11.Gtlz
.

7.0llz, ClIC=0), 3.67 (s
, 3. QCl-13), 4.08 <ill',
Q.1. ．． 1- C1,211Z, (]110)
,4. ! 71 (m, 1, Cll0),! +
, 37' (dd.

1, J=1! i, 4. 7,0112, Vil
lV i ), 5. C33 (dd, 1, J-1
! +, 4. 6.211z) ;CNMII(CDC
3.90MHz, 111111 ) δ14.1.2
2, 7.24.8.25.2.2G, 9.28.0.2
9.0°29.5.31.8.34.0.3t3. ! J
, 47, 9.48.2.51. ! i.

! i4.9.68.1.72.11. 12G, 6.
138,8. 174.4°217.3 TLC': Rf: 0.64 (EtOAc-
cyclol+cxa++c −−1−l−I F =
G: 3: 1) Optical rotation trace: [αco-t-23
,8,” (CLl, 355°Meal) Example 8 9 3.3m9 to 0.5m (7) AC011-1-12
0--r Dissolved in LIF (3:1:1) and heated at 45℃"C
: 711. '+ stirring J'l'l.

Ta. Remove the solvent with a vacuum pump and then remove it with toluene. The solvent was distilled off using silica gel (3 times), and silica gel Kasimuku L171~(M
Purification was performed using Ck silica gel (0.69:ethyl acetate:hexane (3:2)) to obtain 2.0 m7 (yield: 88%) of dandelion as a product.

IR (CIiC3): 3720-3240.17
/lo.

1730cm-1 1'' NMR (CDCu3.90M1-!z, +n+m
) δ : 0.89 (t, 3. J −6,411
z, CI-h), 1.1-2.1 (+n, 2
1. CI-+2 X9. CM, alld ol-
1x2> , 2.32 (+, 2. J= 7.0H
z , C112C00C) , 2.44 ((1,2,
J=2.0+17, Cl12G=0), 2.7
9 (dd, 1, J = 11.6l-lz.

7.0Hz, Cl-10=o), 3. [i? (s
, 3. 0CLl, 3), 4.08 (br, Q, 1.
J = (i, 21-12, CNo), 4.51
(m, 1. Cll0>, 5.37 (dd.

1, J = 15.4. 7. ol-1z, Vi++
y 1 ), 5.63 (dd, 1 , J=1!i, 4
．． 6.2H2): CNMR (CDCS3, 90
M Ll z, 1+1+m ) δ14.1. 22.
7. 24.8. 25,2. 26,9. 2B, 0
．． 29.0°29.5. 31.8. 34.0.
3G, 9. 47.9. 48.2. ! +1. ! l.

54.9. (i8.1.72.8.12[3,G
, 138.8. 174.4゜217.3 Reference 11 A 100 d eggplant flask was heated at -78℃ under an argon stream.
2.6-t-Butyl-4-methylfurinol and dinenobutylaluminium (n toluene solution 0.1
AGwo20.4adlwojinh In l'l' u T
12 dissolved in 6 d of dr. toluene was added thereto using a stainless steel tube. 311" - 20℃ for 7 minutes
After the temperature was raised to , it was stirred at =20°C for 25 hours. After diluting the reaction solution with 10 d of ethyl acetate, 40 d of saturated aqueous sodium hydrogen tartrate solution was added, followed by shaking. The organic layer and the aqueous layer were separated, and after IC, the aqueous layer was extracted with ethyl n1 acid.

(20dX2). The organic layers were combined and dried over anhydrous sodium sulfate. After concentration under reduced pressure, 15 g of MOrck silica gel was subjected to silica gel column chromatography;
The product was 121#1g (yield IR
CUs): 3GOO-3320,172'acm
-'11 NMR (CDCli a, 9QM l-11
, 1111111> 6 :0, (+4 (S, 6.
Si C113X2>, 0.7-1.1<12.
Si C (C113> 3 and C113), 1
．． 1-2.7(if, 31.ClI2X14.C
I-IX 2. alld oil), 3,37 4
．． 3(Ill, 8.OCI+3, cHox3and
C11z O) , 4.67 (II, 1, 0CI
IO).

! i,2-! i, G (m, 2. vinyl) Reference example 2 Place 10 test tubes in an argon stream, -71iY;
'Pour the same reducing agent 111Idl as in Example 1 and stir.'aj<. Dry there -1' 01uelle2
ad! Dissolve in 1. :Add 13 with a stainless steel tube. Heat to -20℃ for 3 hours or 1).
0.83% of reducing agent was added, and the mixture was further stirred at -20°C for 3 hours, and (1,83-) was added again and stirred for 2 hours and 30 minutes. After diluting the reaction solution with 51 dl of ethyl acetate, saturated tartaric acid solution Add thorium acid solution 10- and stir well.
, /ζ. After separating the organic layer, the aqueous layer was diluted with ethyl acetate.
The right 1 m of the extracts (2xlOIIdl) were combined and dried over anhydrous sodium sulfate. After reduced pressure rfA condensation, it was subjected to silica gel column chromatography, (fvlcrc
K sili) Nogle 3; Vinegar: Heyu 1° Zan: Benzene = 1 Ni: 1), product β-26μ (yield 7G%)
I got it.

The properties of this thing were the same in @Example 1.

Claims (1)

[Claims] 1. In the following formula (1), R11 is an alkyl group of 01 to C+o, or 1-(
C1-07) represents a hydrocarbon silyl group, R2 and R3 are the same or different hydrogen atoms, substituted or unsubstituted C
1 to C+a) alkyl group or substituted or unsubstituted 5
- represents a 6-membered cycloal-4-l group, ) (31 represents a tri(C+ to C7) hydrocarbon silyl group, and 1 represents a group that forms a 7-cetal bond with the oxygen atom of hydroxyl) The hydroxyl group at position 9 of the prostaglandin 1α group represented by is occupied by a group that forms a 7L bond with the oxygen atom of the hydroxyl group, and .1(31,1(41 is the same as in F, (:'< l
When l<41, 1iil □- or different from that, it forms an altar bond with the oxygen atom of the hydroxyl group and represents ``Ruri''. Debonding - W1 Then, after converting to 62, if necessary, change the explanation and σ / or R2 in the hydrolysis reaction formula
, R3 is the same as the above definition, 1<1 is Mizuito 1 Kyoko, (/
Represents an alkyl group of I to CIO, and R'' and R6 are the same or violet and represent a group that forms a 7't tar bond with an aqueous group 131 as a child or with an oxygen atom of a hydroxyl group. "M method 2. of prostaglandin D1 class.
Claim 1 wherein the selective 11;2 protection reaction is carried out using Te1haler 11-butylammonium fluoride.
3. Process 3 for producing prostagland γ-in D1 as described in Claim 4; Process 4 for producing prostagland D1 as described in Claim 1, in which the oxidation reaction is carried out using a chromium oxygen oxidizing agent. In the above formula (1), R11 is a del group or a del group. A new process for producing prostaglan gamma-in D1 according to any one of claims 11n to 3 of claim IL11. 5. In the above formula (1), J3 is a hydrogen atom C8, and any of Claims 11Ei to 4th Jlj is i. A new method for producing prostaglandin D1 class as described in Jji. 6. Claims 1 to 5, wherein in the above formula (1), R2 is a 11-pendel group, an n-hexyl group, a 2-medyl-1-hexyl group, a cyclohexyl group, or a cyclopentyl group. Process 7 for producing prostaglandin D1 according to any one of the above formulas (1), where 1 and 31 in the above formula (1) are pulsylsilyl or butyldimedylsilyl, especially the crystallization range i ]1 to 6]P L1 staglandin D+F, fl's "12 people 8," according to any one of j4.
In the above formula (2), J3 is subtracted by C11, and 1<51 is the same or different.
11-xyethyl group, 2-me1-xy-2-JL:l pyl group or (2-meth4-cy]21he4-cy)methy11J Emerging N people of category D+ listed in any one of Section 7