DE2601333A1 - NEW CHEMICAL COMPOUNDS, PROCESSES FOR THEIR MANUFACTURING AND THEIR USE AS INTERMEDIATE PRODUCTS - Google Patents

Description

New chemical compounds, processes for their preparation and their Use as intermediate products The invention relates to new chemical compounds, Process for their preparation and their use as intermediates. The new Compounds are valuable as intermediates in the synthesis of prostaglandins and prostaglandin analogs.

The new compounds according to the invention have the general formula in which B is in the α or β position and is a hydrocarbon radical in which the α carbon atom is activated by a suitable blocked or unblocked functional group, making it oxidizable, preferably to an aldehyde.

Preference is given to compounds according to the invention in which B is a hydrocarbon radical which is substituted by one or more substituted or unsubstituted hydroxyl groups, at least one of which is on the α-carbon atom, for example

and in which R2, R3 and R4 are identical or different and are each for pull a suitable blocking group and R3 and R4 together in a ring system, e.g. a cyclic carbonate, can be incorporated. Appropriate blocking groups are known. Examples are acyl radicals, e.g. benzoyl or acetyl, and substituted or unsubstituted alkyl radicals, preferably lower alkyl radicals with 1 to 4 carbon atoms, to call. Suitable as substituted and unsubstituted blocking alkyl radicals for example trityl, benzyl and methyl.

Examples of particularly preferred compounds of the formula (I) are mentioned: 5,6-di-O-acyl-3-C- (carboxymethyl-2,3-Y-lactone) -3-deoxy-D-gulofuranose; 5,6-di-O-acyl-3-C- (carboxymethyl-2,3-Y-lactone) -) - deoxy-D-allofuranose; 5-0-acyl-3-C- (carboxymethyl-2,3-e-lactone) -3-deoxy-D-ribofuranose; 5-0-acyl -) - C- (carboxymethyl-2,3-Y-lactone) -3-deoxy-L-lyxofuranose; 3-C- (carboxymethyl-2,3-e-lactone) -3-deoxy-D-guloruranose-5, 6-carbonate; 3-C- (carboxymethyl-2,) - z-lactone) -3-deoxy-D-alloruranose-5, 6-carbonate; 3-C- (carboxymethyl-2,3-γ-lactone) -3-deoxy-5-O-methylribofuranose; 3-C- (carboxymethyl-2,3-T-lactone) -3-deoxy-5-0-methyl-L-lyxofuranose.

The compounds of the general formula (I) can be converted into compounds of the general formula (II), which are also new compounds: Here A stands for B has the same meaning as in the compounds of the formula (1), while R and R1, which are identical or different, each represent hydrogen or, together with the oxygen, form a split-off group. Cleaved groups are groups which are cleaved off, for example, for ring closure, on reaction with the corresponding nucleophilic compound. For example, R and R1 can stand for mesyl, tosyl, benzenesulfonyl or triRluoromethylsulfonyl groups.

Preferred of the compounds of the formula (II) are those in which B has the same meaning as in the preferred compounds of the formula (I) with the difference is that R2, R5 and R4 can also be hydrogen.

Of the compounds of the formula (II), the following are particularly preferred: 5,6-di-o-acyl-3-C- (carboxymethyl-2, -lactone) -3-deoxy D-gulit, 5-O-acyl-3-C- (carboxymethyl-2,) - y-lactone) -3-deoxy-L-lyxitol,) -C- (carboxymethyl-2,) - Y-lactone) - ) -deoxy-D-gulitol-5,6-carbonate, 3-C- (carboxymethyl-2,3-Y-lactone) -3-deoxy-5-O-methyl-L-lyxite, 1,4-anhydro-3-C- (carboxymethyl-2v3-Y-lactone) - 3-deoxy-D-allitol, 1,4-Anhydro-3-C- (carboxymethyl-2,) - Y-lactone) -) - deoxy-D-ribitol, and their esters.

Compounds of formulas (I) and (II) are valuable as intermediates for the production of prostaglandins and prostaglandin analogs. For example compounds of the formula (II) which contain the groups OR and OR1, the ring closure with a suitable nucleophile! Reagent are subjected so that the stereochemistry is reversed at C4. The suitable side chains can lead to the compounds with closed ring by oxidation of group B to form a Aldehydes are added, followed by the coupling of a first side chain and reduction of the lactone ring with a subsequent coupling of a second side chain. These Reactions can take place in reverse order. An extremely important one Feature of the respective intermediate products according to the invention is that the Stereochemistry at the carbon atoms C2, C3 and C4 is such that prostaglandins and prostaglandin analogues are formed with natural configuration when the side chains are added. It is these prostaglandins that exhibit biological activity.

It is an important characteristic of the intermediates that the conversion the compounds of the formula (I) into the compounds of the formula (II) stereospecifically runs on the carbon atoms C2, C and C4. This means that the 5 C4 stereochemistry these G atoms can be clearly identified. This is important in the later production of prostaglandins.

The intermediates according to the invention are particularly valuable for the preparation of a new class of prostal glandins which exhibit activity as inhibitors of acid formation by the gastric mucosa and in the contraction or expansion of smooth muscles. These compounds are the subject of another proposal by the applicant and can be represented by the following formula: Here, A stands for -C = O or aC-oOH, IB for R5-C ... OH or R5-C -OH, R5 for H, a lower alkyl radical or substituted lower alkyl radical, Z for CH2-CH2 or 0 = 0 in the cis configuration, R6 and R7, which are identical or different, for H or a substituted or unsubstituted lower alkyl radical, W for -S-, -0- or -CH2-,! Y stands for S -, -0- or -CR10R11-, R8, R9, R10 and R11> which are identical or different, for hydrogen, substituted or unsubstituted lower alkyl radicals or halogen atoms.

The tetrahydrofuran ring can have a hydroxyl group at the C10 position or substituted hydroxyl group and when substituted in this way is substituted, form a ring system with a 9-hydroxy substituent.

These compounds also include their esters.

The compounds of general formula (I) can be based on the stereospecific Ways are established, which is described by the attached formula scheme The importance of this manufacturing route is that the starting materials Sugars of known absolute configuration are stereospecific and each level is Accordingly, the absolute stereochemistry of the compounds (I) is the same as that of the compounds (II) known As already mentioned, this is the case with the production of prostaglandins important, in which the stereochemical relationship of the groups important is.

In the attached shape scheme, B in formula (III) has the same Meaning as in formulas (I) and (II), while B in the formulas (IV) to (VIII) and (XI) has the same meaning as in the formulas (I) and (II) with the difference that if B are those mentioned for the preferred compounds Has meanings, R5 and R4 can also be part of an acetal.

Regarding the formula scheme: a) Compounds of type III, for example D-glucose, D-xylose and L-arabinose, whose absolute stereochemical configuration is known, are converted by known processes into compounds of the formulas in which Y is a group of the formula and R5 and R6, which are identical or different, are alkyl radicals, preferably lower alkyl radicals, hydrogen atoms or a carbocyclic group having 4 to 6 carbon atoms. In particular, Y can be isopropylidene or cyclohexylidene.

b) The compounds IV become compounds V, for example under Use of ruthenium tetroxide (B.T. Lawton, W.A. Szarek and J.K.N. Jones (Carbohydrate Research 10 (1969) 456-458) or dimethyl sulfoxide and anhydrides, e.g. P205 (K. Onodera, S. Hirano and N. Kaschimura, Carbohydrate Research 6 (1968) 276-285) or Acetic anhydride (W. Sowa, Can. J. Chem., 46 (1968) 1586).

c) Depending on the configuration, the connections V become connections VIa or VIb, in which Z is a hydrocarbon radical, for example by a Wittig reaction converted (A. Rosenthal and Nguyen> L. Benzring, J. Org. Ohem.> 34 (1969) 1029). the Compounds VIa contain the group B in the B position, and the compounds VIb contain the group B in the "" position.

d) The compounds VIa are made using a suitable base e.g. DBN (1,5-diazybicyclo-1 4,3,0 -non-5-en) in a dry, of hydroxyl groups free solvent, e.g. benzene, whereby the new compounds VII are obtained isomerized.

e) The compounds VII are stereospecific from the ß-side to known methods such as catalytic reduction using, for example from palladium black in an ether or with Raney nickel in an alcohol to compounds of type VIII.

f) The compounds VIb can by stereospecific reduction of the ß-side can be converted directly into compounds VIII by known methods.

If the compound VIII contains blocking groups R2, R5 and R4, which are acid labile, they are selectively removed and replaced by acid stable groups replaced, e.g. alkylidene by diacyl.

g) The compounds VIII are by removing the blocking Group Y using an aqueous acid, e.g. Acetic acid / water or HCl / aqueous Dioxane converted into new compounds of type IX.

h) The compounds IX are obtained by reduction, for example with Raney nickel in a hot alcohol, converted into new compounds of type X in which R and R1 are hydrogen. If OR and OR1 are a split-off group, the alcohol prepared in the manner described by known methods with the suitable reagent, e.g., mesyl chloride in pyridine / solvent, be esterified.

The compounds IX form a group within the group of by the compounds defined by formula (I), and the compounds X form a group within the group of compounds defined by the formula (II). In the Formulas IX and X have B, R and R1 the same meanings as in the formulas (I) or (in).

i) The compounds of the formula VIa are converted into compounds of the formula XI by using stereospecific reduction from the ß-side, for example a catalyst such as palladium carbon (A. Rosenthal and Nguyen, LT Benzing, J. Org. Chem., 54 (1969) 1029) or Raney nickel converted into an alcohol.

Compounds of type VIII can be used as by-products of this reaction sequence appear.

If the compound XI contains blocking groups R2, R5 and R4, which are acid labile, they are selectively removed and replaced by acid stable groups replaced, e.g. alkylidene by diacyl.

j) Compounds XI are made by removing the blocking group Y converted into new compounds XII with aqueous acid. The compounds XII can by reaction with a suitable halogen acid in a solvent, e.g., a dry acid or a dry acid free from hydroxyl groups; Solvent, optionally containing an acid chloride or by treatment with an anhydride and either subsequent reduction of the halogen-substituted intermediate with a suitable catalyst, e.g. 10% palladium carbon, in the presence of Hydrogen and a nitrogenous base, e.g. a trialkylamine, or by Implementation with the salt of one; Alkyl or aryl mercaptans with formation of the corresponding Mercapto intermediate and subsequent desulfurization, e.g. with Raney nickel, or by acylation the hydroxyl group and treatment with an alkyl or aryl mercaptan in the presence a Lewis acid., e.g. B. BF3 etherate, with formation of the corresponding mercapto intermediate and subsequent desulfurization into the compounds, for example with Raney nickel XIII to be converted. The conversion of compounds XII into compounds XIII can also be achieved by treatment with a suitable acid chloride or acid anhydride with subsequent reaction with a suitable halogen acid in a dry, of hydroxyl-free solvents. The halogen-substituted intermediate is then treated in the manner described above, with compounds XIII can be obtained.

k) Compounds XII are a group within the group of compounds of formula (I), and the compounds XIII are a group within the group of compounds of the formula (II). B in compounds XII and XIII has the same Meaning as in formulas (1) or (in).

The invention also includes a method of those described above Kind that starts at any stage and goes through to the end, and the making of the various new intermediates.

The new compounds and the processes for their preparation will be further explained in the following examples. In these examples behave Parts by weight to parts of volume as well as kilograms to liters.

Example 1 Preparation of 1,2: 5,6-Di-O-isopropylidene-α-D-glucofuranose (Type IV compound) 600 parts by weight of anhydrous D-glucose, 4000 parts by volume of zinc chloride dry acetone, 480 parts by weight anhydrous; powdered zinc chloris and 50 Parts by volume goat orthophosphoric acid and 100 parts by weight of anhydrous copper sulfate were stirred mechanically for 30 hours at room temperature. The undissolved glucose was filtered off and washed with acetone. The filtrate was cooled to 0 ° to 500 °, made alkaline with sodium hydroxide () 40 parts by weight in) 40 parts by weight of water) and filtered. The filtrate was reduced to remove the solvent Pressure evaporated and the residue diluted with water and extracted with chloroform. The combined chloroform extracts were washed with water, concentrated and dried and evaporated, whereby 462 parts by weight (91, based on recovered glucose) raw product obtained in the form of white crystals, melting point 95-101 ° C became. Recrystallization from hexane / chloroform (2: 1) gave the desired Product with a melting point of 105 to 1090 ° C. is obtained. Example 2 Preparation of 1,2: 5,6-di-O-siopropylidene-α -D-ribohexofuranos-3-ulose (type V) using ruthenium dioxide 80 parts by weight 1,2: 5,6-Di-O-isopropylidene-a-D-glucofuranose were warm carbon tetrachloride in 500 parts by volume solved. At room temperature, 100 parts by volume became saturated sodium bicarbonate solution added to form a two-phase mixture. In 100 parts of the room Sodium metaperiodate was dissolved in 1 part by weight of ruthenium dioxide. The ruthenium tetroxide obtained was extracted into carbon tetrachloride. The extract was stirred well added to the two-phase mixture. Once the solution turns black became, 10X aqueous sodium metaperiodate solution was added until a yellow-green color appeared. The reaction was carried out by thin layer chromatography on silica gel Use of hexane / ethyl acetate (3: 2) followed. After the reaction was complete 10 parts by volume of isopropyl alcohol are added, whereupon the mixture is replaced by diatomaceous earth "Celite" was filtered. The carbon tetrachloride layer was washed with aqueous sodium thiosulfate washed and evaporated under reduced pressure to give the hydrate of the ketone was obtained. By distilling the hydrate at a bath temperature of 120 ° C and 0.1 mmHg, the desired compound was obtained in 78% yield I.R. (CHCl3) 1 mm light path, #max. 1770 cm (C = O).

Example 3 Preparation of 1,2: 5, 6-di-o-isopropylidene-a -O-ribohexafuranos-3-ulose (Type V) using dimethyl sulfoxide and acetic anhydride A mixture of 1,2: 5,6-di-O-isopropylidene-D-glucofuranose (26 parts by weight) in dimethyl sulfoxide (150 parts by volume) and acetic anhydride (100 parts by volume) was 48 hours at room temperature shaken well. The solvents were distilled off under reduced pressure. The residue was distilled at 0.1 mm Hg at a bath temperature of 120 ° C, whereby 21 parts by weight of an oil were obtained.

I.R. (CHCl3) 1 mm light path Vmax. 1770 cm (C = O).

Sowa, W. Can. J. Chem. 46 (1968) 1586.

Example 4 Preparation of 3-C-carbonethoxymethylene-3-deoxy-1,2: 5,6-di-O-isopropylidene-α-D-ribo-hexofuranose (Type VIa) A solution of 53.8 Parts by weight of triethyl phosphonoacetate and 12 parts by weight of potassium tert-butoxide in 150 Volume parts of anhydrous dimethylformamide became one at OOC solution of 42 parts by weight of 1,2: 5,6-di-O-isopropylisden-α-d-ribohexofuranos-3-ulose given in 150 parts by volume of dry dimethylformamide under positive nitrogen pressure.

The mixture was at 0 ° under nitrogen for one hour and then at Room temperature stirred well for 48 hours. The solvent was reduced under Pressure removed.

Hexane was added to the residue. After filtration it became The filtrate was evaporated to dryness under reduced pressure. The semi-crystalline solid was chromatographed on silica gel using hexane / ethyl acetate first cleaned in a volume ratio of 4: 1 and then in a volume ratio of 3: 2. Here, 56 parts by weight of a crystalline product were behaved, that of petroleum ether was recrystallized from boiling point 40 to 60 ° C. Melting point 71 to 72 0C (needles).

N.M.R. in CDCl3: # 6.34 (q, C-11 H, J J1 ', 2 = = 1.25 Hz and J X = 2.0 Hz); # 5.84 (d, H-1, J1.2 = 4.0 Hz) # 5.72 (second, H-2 J2.1 = 4.0 Hz and J2.1 '= 1.25 Hz) 64.66 (m, H-4) # 4.05 (m, H-5 and H-6) # 4.23 (q, -CH2-CH3, J = 7.0 Hz) # 1.30 (t -CH2-CH3, J = 7.0 Hz) # 1.36 :; # 1.40; # 1.44 and 1 # 1.50 (4s, C (CH3) 2) I R CCl4 1 mm beam path #max 1730 (C = 0 ester) c, -1 1680 (C = C) cm-1 Elemental analysis: Found: C, 58.47 H 7.31 Calculated for C16H24O7: C 58.52 H 7,) 6 Example 5 Manufacture of 3-C-carboethoxymethyl-3-deoxy-1,2: 5,6-di-o-iospropylidene-α-D-ervthro-hex -) - enofuranose (Type VII, new compounds) 10 parts by weight of 3-C-carboethoxymethylene-3-deoxy-1,2: 5,6-di-o-isopropylidene-α-D-ribo-hexofuranose were in 5 room! share dry benzene dissolved. 3.73 parts by weight were added to the solution 1,5-dizabocyclo- {4.3.0} -non-5-ene (DBN) given. The mixture was at 48 hours Room temperature (260C) stirred under nitrogen. The reaction was monitored by thin layer chromatography using silica gel and hexane / ethyl acetate (volume ratio 3: 2) followed.

The disappearance of the starting material can be achieved by spraying the plate followed with 9.5% chromic acid in 80% sulfuric acid with subsequent heating will.! After the completion of the reaction, the solvent was reduced under reduced pressure removed and the product by using column chromatography on silica gel of hexane / ethyl acetate (volume ratio): 2) purified, with 7.4 parts by weight pure Product as a pale yellow oil.

N.M.R. in CDCl3: # 5.99 (d, J6Hz, 1H); 65.31 (d, J6Hz, iH); 64.71 (t, J7Hz, IH); # 4.24-3.91 (m, 4H); 63> 43-3.19 (q, J17Hz; 2H); 61.43 (s, 9H); 61.36 (s, 3H); # 1.26 (t, J7Hz, 3H) I.R. in CHC13, 1 mm beam path, #max. 1755 (C = O, ester) cm-1 Example 6 Preparation of 3-C-carboethoxymethyl-3-deoxy-1,2: 5,6-di-Q-isopropylidene-a -D-gulofuranose (new compounds of type VIII) 0.1 parts by weight freshly prepared 3-O-Oarboethoxymethyl- 3-deoxy-1,2: 5,6-di-O-isopropylidene-α-D-erythro-hex-3-enofuranose in 5 parts by volume of dry ether was added to 0.2 parts by weight of palladium black. The mixture was shaken under hydrogen at a pressure of 1.2 kg / cm² for 5.5 hours. The mixture was filtered.

Evaporation left 0.09 part by weight of a crystalline product obtained from melting point 80 to 82 ° C (needles).

N.M: R. in CDCl3: # 5.81 (d; H-1, J1.2 = 4.0 Hz) 64.70 (t, H-2, J = 4.0 Hz) 2> 3 I.R. in CHCL3: 1 mm beam path, #max. 1735 / C =) 0 ester) cm Elemental analysis: Found: C 58,) 2 H 7.86. Calculated for C16H26O7: C 58.17 H 7.9) Example 7 Preparation of 3-C-carboethoxymethyl-3-deoxy-1,2-O-isopropylidene-D-gulofuranose (type VIII) 1 part by weight of 3-C-carboethoxymethyl-3-deoxy-1,2: 5,6-di-O-isopropylidene-D-gulofuranose in acetic acid / water (volume ratio 3: 2) was 30 minutes at 70 ° C in one open flask stirred. The mixture was cooled to OOC and added 3.45 parts by weight Potassium carbonate neutralized. After adding 30 parts by volume of acetone, the mixture became filtered. The residue was washed with acetone. The combined filtrates were evaporated to dryness. The residue was purified by column chromatography on silica gel first using chloroform and then using 5 ffi methanol / chloroform (volume ratio) purified, with 0.2 parts by weight of the desired compound were obtained in the form of an oil.

N.M.R. in CDCl3 # 5.83 (d, J1,2 = 4Hz, H-1) # 4.76 (t, J1,2 = 4Hz, H-2) # 3.04 (s, OH) # 4.15 (q, J = 8Hz, -CH CH3) ', 26 (t, J = 8HZ, -CH CH3) IR. CHCl3. 1 mm beam path #max. 3450 (-OH) cm-1 1720 (-C = O) cm Example 8 Preparation of 5,6-Do-O-acetyl-3-C-carboethoxymethyl-3-deoxy-1,2-O-isopropylidene-α-D-glucofuranose (Type VIII) 0.74 parts by weight of acetic anhydride and 0.6 parts by weight of pyridine were to 1 part by weight of 3-C-carboethoxymethyl-3-deoxy-1,2-isopropylidene-D-gulofuranose given in 10 parts by volume of chloroform. The mixture was left for 56 hours at room temperature (260C) stirred. The mixture was diluted with ice cold% hydrochloric acid. The chloroform solution was washed with the acidic solution to remove all traces of pyridine. The Ohloroform solution was washed with saturated aqueous sodium bicarbonate and then with water and dried over anhydrous sodium sulfate. By removing the chloroform 0.98 part by weight of the desired compound was obtained under reduced pressure.

I.R. in CHCl3, 1 mm beam path #max. 11730 cm-1 (C = 0, wide) example 9 Preparation of 5,6-di-O-acetyl-3-C- (carboxymethyl-2,3-γ-lactone) -3-deoxy-D-ulofuranose (Type IX) 1% by weight; 5,6-Di-O-acetyl-3-C-carboethoxymethyl-3-deoxy-3-deoxy-1,2-0-isopropylidene -D-gulofuranose was in 20 parts by volume acetic acid / water (volume ratio 1S: 1) solved.

The solution was stirred at 90 ° C. for 6 hours. The solvent was removed under reduced pressure and the remaining water as an azeotrope with benzene removed. The product was purified by using column chromatography on silica gel Purified by 2 ß methanol / chloroform, with 0.53 parts by weight of a crystalline Product of melting point 118 to 120 ° C were obtained.

-l I.R. in CHORUS, 1 mm beam path, #max. 5450 (-OH) cm 1810 (lactone) cm -l 1725 (C = O ester) cm 1 Example 10 Preparation of 5,6-Di-Q-acetyl-3-C- (carboxymethyl-2,3-γ-lactone) -3-deoxy-1,4- di-O-mesyl-D-gulit (Type X) 0.3 part by weight of 5,6-di-O-acetyl-3-C- (carboxymethyl-2,3-γ-lactone) -3-deoxy-D-gulofuranose were with 1 part by weight of Raney nickel in 25 parts by volume of boiling ethanol for 1.5 hours reduced. The solution was filtered and the filtrate was evaporated to dryness. The residue was dissolved in 5 parts by volume of dry pyridine and 5 parts by volume of chloroform solved. After adding 0.23 parts by weight of mesyl chloride, the mixture became 16 hours held at 0 ° C. The chloroform solution was mixed with cold% hydrochloric acid and then washed with aqueous saturated sodium bicarbonate solution and finally with water. The solvent fraction was dried over anhydrous sodium sulfate, filtered and evaporated to dryness to give 0.18% by weight of an oil.

I. R. (CHCl3), 1 mm Stahlenweg, #max 1790 cm-1 (C = 0 lactone) 1740 cm (C = O ester) 1355 cm-1 (SO2) Example 11 Preparation of 3-C-carboethoxymethyl-3-deoxy-1,2: 5,6-di-O-isopropylifden-α -D-allofuranose (Type XI) A solution of 55 parts by weight of triethylphosphonacetate and 15.8 parts by weight of potassium tert-butoxide in 75 parts by volume of anhydrous dimethylformamide became a solution of 56.8 parts by weight of 1,2: 5,6-di-0-isopropylidene-D-ribohexofuranos-D-ulose at 0 ° C given in 75 parts by volume of dry dimethylformamide under psitivem nitrogen pressure. The mixture was left under nitrogen at 0 ° C for one hour and then at room temperature Stirred well for 48 hours. The solvent was removed under reduced pressure and the residue extracted four times with 100 parts by volume of dry hexane. the combined hexane extracts were filtered and evaporated to give a syrup, the crystallized on standing. After adding 30 parts by weight Raney nickel in 100 parts by volume of methanol, the mixture was 5.5 hours at room temperature shaken under hydrogen (pressure 2 atm.). By filtration and evaporation of the A syrupy residue was obtained by solvent, which was determined by column chromatography was purified on silica gel using chloroform as the eluant.

The product obtained from the column was recrystallized from cyclohexane, 55 parts by weight of the desired compound from melting point 90 to 9100 (needles) were obtained.

N.M.R, in CDCl3:: (55.75 (d, H-1, J = 4.0 Hz) # 4.78 (t, H-2-J2.3 1.2 = 4.0 Hz) # 2.32 (m, H-3) # 4.14 (q, -CH2-CH3, J = 7.0 Hz) # 1.26 (t, -CH2-CH3 , J = 7.0 Hz 61.29; 61.31; 61.39 and # 1.48 {4s, C (CH3) 2} I.R. CC14.1 mm beam path, #max 1730 (C = O ester) cm Elemental Analysis: Found: C 58.55 H 7.88 Calculated for C16H2607: C 58.17 H 7.9) On larger scale preparations became crystalline 3-carboethoxymethyl-3-deoxy-1,2: 5,6-di-O-isopropylidene-α-D-gulofuranose the column chromatography described above was isolated. The connection was purified by recrystallization from petroleum ether (boiling point 40 to 600C). Melting point 80 to 82 ° C.

Example 12 Preparation of 5,6-di-O-acetyl-3-C-carboethoxymethyl-3-deoxy-1,2-O-isopropylidene-α-D-allofuranose (Type XI) 33.4 parts by weight of 3-C-carboethoxymethyl-3-deoxy-1,2: 5,6-di-O-isopropylidene-α -D-allofuranose in 100 parts by volume of acetic acid / water (volume ratio 4: 1) Heated to 70 ° C for 40 minutes. the mixture was cooled in an ice bath, leaving 160 Parts by weight of potassium carbonate were added in portions. After adding 500 parts Acetone, the mixture was filtered through a pad of "Celite" diatomaceous earth. That The filtrate was evaporated. The residue was dissolved in 250 parts by volume of chloroform and filtered. A syrup was obtained by evaporation of the filtrate Column chromatography using silica gel as the stationary phase and initially under the use of Chloroform and then chloroform / methanol (volume ratio 97.5: 2.5) was purified as the eluent, with 22.4 parts by weight of the pure desired Compound as a colorless oil.

I.R. CHCL3, 1 mm beam path, #max. 3500 (OH) cm-1, 1755 (C = O.Ester) cm 1 88 parts by weight of 3-C-carboethoxymethyl-3-deoxy-1,2-O-isopropylidene-D-allofuranose in 50 parts by volume of dry chloroform became 52.7 parts by weight of dry pyridine in 68.2 parts by weight of acetic anhydride.

The mixture was allowed to stand at room temperature for 28 hours. To Addition of 300 parts by volume of chloroform was the mixture first with water, then extracted with 5% hydrochloric acid and then with 5% aqueous sodium bicarbonate. The chloroform layer was dried over anhydrous sodium sulfate, filtered and evaporated to dryness under reduced pressure to give a syrup became. By purifying the syrup by column chromatography using silica gel and hexane / ethyl acetate (volume ratio 4: 1) were 88 parts by weight of the desired Compound (after recrystallization from petroleum ether from boiling point 40 to 60 ° C) from Melting point 53 to 54 ° C (needles) obtained.

N.M.R. in CDCl3: 65.79 (d, H-1, HJf = 3.7 Hz) (55.08 (m, H-5) # 4.78 (t, H-2, J2.3 = 4.0 Hz) + # 4.14 (q, -CH2-CH3, J = 7.0 Jz) # 4.04-4.50 (m, H-6 and H-6 ') # 3.95 (dd, H-4, J3.4 = 10 Hz and) J4.5 = 5.0 Hz) # 2.2-2.9 (m, H-1 'and H-3) 62, 02 and 62.04 (2s, CH3-CO-) # 1.48 and # 1.30 {2s, C (CH3) 2} # 1.26 (t, -CH2-CH3-, J = 7.0 Hz) IR. 1 mm beam path, max 1740 (wide 0 = 0 ester) cm 1 elemental analysis: Found: C 54.26 H 6.95 Calculated for C17H2609: C 54.53 H 7.00 Example 13 Preparation of 5,6-di-O-acetyl-3-C- (carboxymethyl-2,3-γ-lactone) -3-deoxy-D-allofuranose (Type XII) 36.2 parts by weight 5,6-di-O-acetyl-3-C-carboethoxymethyl-3-deoxy-1,2-O-isopropylidene-α- -D-allofuranose were in 200 parts by volume acetic acid / water (volume ratio 4: 1) dissolved, the solution was heated to 90 ° C. for 3 hours. The solvent was taking evaporated under reduced pressure and the remaining water removed as an azeotrope with benzene. The purification of the Rüokstandes by column chromatography on silica gel, where as Eluent first hexane / ethyl acetate in a volume ratio of 3: 2, then Using 1: 1 and then 2: 3 gave 20 parts by weight of the pure desired compound in the form of an oil.

N.H.R. in CDCl3: # 5.56 (s, H-1) 65.18 (m, H-5) # 4.88 (d, H-2 J2.3 = 6.0 Hz) 64.0-4.56 (m, H-4, H-6 and H-6 ') 62.40-3.24 (m, H-1' and H-3) 62, 08 and 2.10 (2s, CH3 -CO-) I.R. CHCl3, 1 mm beam path, #max. 3420 (OH) cm-1 1785 (C = o) Lactone) cm-1 and 1735 (C = O ester) cm-1 by treating 0.1 part by weight of these Compound with acetic anhydride (IV) and pyridine (IV) were made after usual isolation 0.08 part by weight of crystalline 1,5,6-tri-O-acetyl-3-C- (carboxymethyl-2,3-γ-lactone) -3-deoxy-B-D-allofuranose from melting point 106 to 107 ° C (Platelets) received, N.M.R. in CDCl3: # 6.34 (s, H-1) # 5.09 (m, H-5) # 4.93 (d, H-2, J2.3 = 6.0Hz) 64.18 (dd, H -4, J = 4.0 Hz and J = 8.5 Hz) # 4.58-3.88 (m H.-6 and H-6 ') 63.26-2.40 (m, H-1' and H-3) 62.04; 62.10 and 62.11 (3s, CH -CO-) I.R. CHCl3, 1mm beam path, #max. 1785 C = 0 lactone) cm -1 and 1750 (C = 0 ester) cm -1 Elemental analysis: Found: C 50.95 H 5.44 Calculated for C14H1809: C 50.93 H 5.49 Example 14 Preparation of 5,6-di-O-acetyl-1,4-anhydro-3-C- (carboxymethyl-2,3-γ-lactone ) -3-deoxy-D-allitol (Type XIII) via mercapto intermediates a) 7.2 parts by weight of 5,6-di-O-acetyl-3-C- (carboxymethyl-2,3-y-lactone) -3-deoxy-D-allofuranose , 5 parts by weight of 4-nitrobenzoyl chloride, 2.2 parts by weight of pyridine and 100 parts by volume dry Chloroform was stirred at room temperature for 24 hours. After adding 10 parts of the room Water, the mixture was stirred for 50 minutes. The chloroform phase was treated with ln-sulfuric acid, aqueous sodium bicarbonate and water washed over anhydrous sodium sulfate dried and filtered. Evaporation of the solvent left 10.4 parts by weight 5,6-Di-O-acetyl -) - C- (carboxymethyl-2,) - Y-lactone) -3-deoxy-1-0-p-nitrobenzoyl-D-allofuranose obtained as a syrup. This compound was in 100 parts by volume of dry dichloromethane solved. The solution was cooled to 0 ° C followed by 0.75 hours of dry HBr gas was passed through. the Bottle was sealed and 72 hours held at 40C. The mixture was used to remove the p-nitrobenzoic acid formed filtered. The filtrate was taken under reduced pressure at a temperature below 50 0C evaporated. A solution of 2.93 parts by weight of thiophenol was added to the residue and 1.35 parts by weight of potassium hydroxide in 50 parts by volume of ethanol. The mixture was heated to 50 to 60 ° C. on the water bath for 50 minutes. The solvent was evaporated and the residue chromatographed on column using silica gel purified from hexane / ethyl acetate (volume ratio 3: 2) as eluent. That Product obtained from the column (7.7 parts by weight) yielded after recrystallization Chloroform / ether crystalline phenyl-5,6-di-O-acetyl-3-C- (carboxymethyl-2,3-e-lactone) -1,) - dideoxy- | 1-thio-α-D-allofuranoside, melting point 113 to 1150C (needles).

N.M.R. in CdCl3: # 7.2-7.56 (m, phenyl) # 5.76 (d, H-1, J1.2 = 5.0 Hz) and # 5.20 (dd, H-2, J1.2 = 5.0 Hz) and J2.3 = 7.5 Hz. By irradiating the H-1 signal At # 5.76 the H-2 signal collapsed to a doublet of J2.3 = 7.5 Hz.) 65.18 (m, H-5) # 4.52-4.0 (m, H-4, H-6 and H-6 ') # 3.16-2.44 (m, Hl' and H-3) # 2.04 and 2.08 (2s, CH3-CO-) I.R. CHCl3; 1 mm beam path, Vmax. 1790 (C = 0 lactone) cm-1 and 1745 (C = 0 ester) cm-1 Elemental analysis: Found: C 56.95 H 5.19 Calculated for C18H20SO7: C 56.83 H 5.301 b) To a solution of 70 parts by weight of 1,5,6-tri-O-acetyl-3-C- (carboxymethyl-2,3-Y-lactone) -3-deoxy-ß-D- l allofuranose in 500 parts by volume of dry benzene became 10.5 parts by volume of BF3 etherate and 27.4 parts by weight of thiopehnol. The mixture was left for 16 hours at room temperature touched. After adding 500 parts by volume of ether, the mixture was twice with 100 Parts of the volume of saturated sodium bicarbonate solution extracted. The organic layer was dried over Na2SO4 and evaporated under reduced pressure. Crystallization of the residue from chloroform-ether gave 60 parts by weight of phenyl-5,6-di-0-acetyl-3-C- (carboxymethyl-2,3-Y-lactone) -1,3-dideoxy-1-thios -D-allofuranoside with a melting point of 113 to 115 ° C. [α] 23 D + 248 (c 1.2 CHCl3). The mother liquor (10 parts by weight) gave after chromatography on silica gel using of hexane / ethyl acetate as eluent initially in a volume ratio of 4: 1 and then from 3: 2 and 1: 1 a further 2 parts by weight of the 1-α-phenyl mereapto compound and 6 parts by weight of the corresponding 1-β isomer (total yield 84).

1-ß-Phenylmercaptoiosmeres: melting point 82-830C [α] D21.5 - 178 ° (c 3.2 CHCl3) Elemental analysis: Calculated for C18H20S07: C 56.7 H 5.1 Found: C 56.8 H 5.3 N.M.R. (CDCl3 - 60 mHz) # 5.6 (d, H-1 J1.2 # 1 Hz) # 5.01 (dd, H-2 J2.1 # 1 Hz and J2,3 = 6 Hz).

7 parts by weight of the mercapto intermediate of (a) or

(b) in 75 parts by volume of ethanol containing 35 parts by weight of Raney nickel, were refluxed for 2 hours. By filtration and evaporation of the solvent 4.5 parts by weight of 5,6-di-O-acetyl-1,4-anhydro -3-C- (carboxymethyl-2,3-Y-lactone) -3-deoxy-D-allitol obtain. Purification by using column chromatography on silica gel of hexane / ethyl acetate initially in a volume ratio of 4: 1 and then 1: 1 gave 4 Parts by weight of a bls.

N.M.R. in CDCi3: 65.05 (m, H-2 and H-5) 64.52-3.92 (m, H-1 and tt-6) 3.85 (dd, H-4, J3.4 = 7.5 Hz and J = 5.5 Hz) 4, S 62.95-2.50 (m, H-1 'and H-3) 62, 05 and 62.07 (2s, CH -CO-) M.R. CHCL3, 1 mm beam path, #max. 1790 (C = 0 lactone) cm-1 and 1750 (C = 0 ester) cm-1 Elemental Analysis: Found: C 52.63 H 5.94 Calculated for C12Hl607: C 52.84 H 5.92 Example 15 1,4-Anhydro-3-C- (carboxymethyl-2,3-γ-lactone) -3-deoxy-D-allitol (New compounds of type XIII) A mixture of 4 parts by weight of 5,6-SDi-O-acetyl-1,4-anhydro-3-C- (carboxymethyl-2,3-z-lactone) -3-deoxy -D -allit and 4 parts by weight of anhydrous potassium carbonate in 40 parts by volume of Mwethanol / waser (Volume ratio 5: 3) was heated to 70 ° C. for 2 hours. The solution was then using acidified to pH 3 with the ion exchange resin "Dowex 50 W" and filtered. The filtrate was evaporated, the remaining water being removed as an azeotrope with benzene and a syrup was obtained which crystallized when left to stand. By Recrystallization from methanol / ether or absolute ethanol / ether was 2.5 parts by weight crystalline needles with a melting point of 134 to 13500 are obtained.

Elemental analysis: Found: C 51.04 H 6.31 Calculated for C8H1205: C 51.05 H 6.42 Similarly, the following compounds were made: 1. 1,2-O-isopropylidene-α- -D-xylofuranose (compound of type IV) from D-xylose (P.A. Levene, A.L. Raymond, J. Biol. Chem., 102 (1933) 317). Colorless oil that slowly crystallized. Melting point 34 to 400C.

2,5-O-Benzoyl-1,2-O-isopropylidene-α-D-xylofuranose (compound of type IV). (P.A. Levene, A.L. Raymond, ibid.) White needles made from chloroform / hexane, Melting point 83 ° C.

I R. CHCl3. 1 mm beam path # max 3470 (-OH) cm 1710 (-C = O) cm 1600 (-C = C-) cm -1 3. 5-O-Benzoyl-1,2-O-isopropylidene-α-D-erythro-pentofuranos-5-ulose (Type V compound) (G.L. Tong, W.W. Lee and L. Goodman, J. Org. Chem., 32 (1967) 1984). White needles made from ether / chloroform / hexane, melting point 94 to 9500.

4. 5-O-benzoyl-3-C-carbomethoxymethyl-3-deoxy-1,2-0-isopropylidene-α -D-ribofuranose (new compound of type XI). Fine white needles made of chloroform / hexane, Melting point 86 to 87 ° C.

-1 I, R. CHCl3 1 mm beam path v max 1720 (C = 0) cm 1600 (-C = C-) cm-1 N.M.R. in CDCl3 # 5.86 (d, J1.2 = 4Hz, H-1); - 6 4.80 (t, J2,1 = 4Hz, H-2); 6 3.66 ( s, OCH3); # 1.50; 1.31 (2s, C (CH3) 2) Analysis - Found: C, 61.66 H 6.21. Calculated for C18H2207: C, 61.70 H.G., 33.5.5-0-BenzOyl-3-C- (carboxymethyl-2,3-z-lactone) -3-deoxy-D-ribofuranose (new compound of type XII). Fine white needles made from acetone / petroleum ether, boiling point 60 to 800C. Melting point 114 to 11500.

I.R. Chloroform, 1 mm beam path v max 3400 (wide-OH) cm-1 1790 (-C = O lactone) cm-1 1720 (-C = O ester) cm 1600 (-C = C-) cm-1 N.M.R. in CDCl3 # 5.60 (s, H-1) # 4.91 (d, s = 6 Hz, H-2) 2.3 Analysis - Found: C 60.45 H 5.05 Calculated for C14H14O6: C 60.43 H 5.07 6. 5-O-Benzoyl-3-C- (carboxymethyl-2,3, -γ-lactone) -3-deoxy-1-o- (p-nitrobenzoyl) -β -D-ribofuranose. Fine white needles made of ethyl acetate / petroleum ether with a boiling point of 60 to 8000. Melting point 130 to 132 ° C.

I R. CHCl3 1 mm beam path v max 1800 (C = O lactone) cm-1 1735 (C = O Ester) cm-1 1530 (N02) cm N.M.R. in CDCl3 # 6.63 (s, H-1) 6 (d, J = 6 Hz, H-2) analysis - Found: C 58.68 t (3.98 range for C21H17NO9: C 59.00 H 4.01 7. Phenyl-5-0-benzoyl-3-C- (carboxymethyl-2,3-e-lactone) - 1,3-dideoxy-1-thio-α -D-ribofuranoside. Fine white needles made from ethyl acetate / hexane, melting point 129 bis 130 ° C.

I.R. CHCl3, 1 mm beam path, T max. 1795 (C = O lactone) cm-1, 1725 (C = O ester) cm-1 N.M.R. in CDCl3 # 5.81 (d, J1,2 = 5 Hz, H-1) # 5.23 (dd, J1,2 = 5 Hz, J2.3 = 7.5 Hz, H-2) Elemental analysis: Found: C 64.51 H 4.86 Calculated for C20H18O5S: C 64.85 H 4.89 8. 1,4-Anhydro-5-0-benzoyl-3-C- (carboxymethyl-2,3-8-lactone) -3-deoxy-D-ribitol (Compound of type XIII). Crystalline needles made from ethyl acetate / petroleum ether, boiling point 60 to 800C, melting point 130 to 133 ° C.

I R. chloroform, 1 mm beam path v max 1785 (C = O lactone) cm 1 1725 (C = O ester) cm 1 N.-M.R. in CDCl3 # 8.06 - 7.22 (m, phenyl) # 5.03 (m, H-2) 64.54 - 3.90 (m, H-1, H-4, H-5) # 3.00 - 2.44 (m, H-1, H-3) Analysis: Found: C, 64.31- H 5.38. Calculated for C14H14O5: C 64.57 H 5.33 9. 1,4-Anhydro-3-C- (carboxymethyl-2,3-Y-lactone) -3-deoxy-D-ribitol (Compound of type XIII). Manufactured as an oil, which is revealed by thin layer chromatography Moved on silica gel as single spots (verified with iodine vapors).

I.R. CHCl3, 1 mm beam path, # max. 3490 (wide, OH) cm-1 1790 (C = O Lactone) cm-1 10. 5,6-Di-O-Benzoyl-: i -C -carbomethoxymethyl-3-deoxy-1,2-0-isopropylidene-α-D-allofuranose (Connection of type XI). Crystals from methanol / ether. Melting point 63 to 65 ° C (Needles).

I.R. in CHCl3, 1 mm beam path, #max 1730 (C = O ester) cm-1, 1600 (C = C) cm-1 N.M.R. in CDCl3 # 8.08 - 7.24 (m, phenyl) # 5.83 (d, H-1, J1.2 = 4 Hz) # 4.79 (t, H-2, J2.3 = 5 Hz) 3.55 (s, OCH3) Elemental Analysis: Found: C 64.14 H 5.71 Calculated for C26H2809: C 64.48 H 5.82 11. 5,6-Di-O -benzoyl-3-C- (carboxymethyl-2,3-γ-lactone) -3-deoxy-D-allofuranose (Compound of type XII).

Ether crystals, melting point 123 to 124 ° C.

N.M.R. in CDCl3: # 5.62 (s, H-1) # 4.92 (d, J2.3 = 6 Hz, H-2) I.R. CHCl3, 1 mm beam path, #max. 1780 (C = O lactone) cm-1, 1730 (C = O ester) cm-1, 1600 (C = C) cm-1 Elemental Analysis: Found: C 64.15 H 4.86 Calculated for C22H20O8: C 64.04 H 4.89 12. Phenyl-5,6-di-O -benzoyl-3-C- (carboxymethyl-2,3-γ-lactone) -1,3-dideoxy-1-thio-α-D-allofuranoside.

Crystals from chloroform / methanol. Melting point 137 to 13800 (needles).

N.M.R. in CDCl3 # 5.82 (d, J1,2 = 5 Hz, H-1) # 5.22 (dd, J2,3 = 7.5 Hz, J1,2 = 5Hz, H-2) I.R. CHCl3, 1 mm beam path, #max. 1790 (C = 0 lactone) cm-1, 1730 (C = O ester) cm-1, 1600 (C = C) cm-1 Elemental Analysis: Found: C, 66.24 H 4.63. Calculated for C28H24S07: C 66.68 H 4.79 13. 1,4-Anhydro-5,6-di- O -benzoyl-3-C- (carboxymethyl-2,3-γ lactone) -3-deoxy-D-allitol (compound of type XIII).

Crystals from chloroform / ether, melting point 126 to 127 ° C (needles).

N.M.R. in CDC1 3 64.87-4.43 (m, H-1) # 5.11 (m, H-2) I R. CHCl3 1 mm beam path v max 1790 (C = 0 lactone) cm-1 1730 (C = O ester) cm-1 analysis - found: C 66.62 H 5.00. Calculated for 022H2007: C 66.65 H 5.09 14. 5-0-Benzoyl-1,2-0-isopropylidene-β-L-arabinofuranose (Type IV).

Prepared as described (E.M. Lacton, K.J. Ryan and L. Goodman, J. Am. Chem. Soc., 86 (1964) 5352, E.J.

Reist, P.A. Hart, L. Goodman and B.R. Baker, ibid, 81 (1959) 5176). Fine white needles made of benzene / petroleum ether, boiling point 40 to 6000. Melting point 146 to 147 ° C.

I.R. CHCl3, 1 mm beam path, v max. 1725 (C = O) cm-1 15. 5-O-Benzoyl-1,2-O-isopropylidene-ß-L-threo-pentofuranos-3-ulose (Type V).

Fine white needles made from diethyl ether, melting point 85 to 87 ° C.

I.R. CHCl3, 1 mm beam path, #max. 1727 (C = 0 ester) cm-1, 1780 (C = O Ketone) cm-1 N.M.R. in CDCl3 # 6.05 (d, J1.2 = 4Hz, H-1) # 1.50, 1.40 (2s, C (CH3) 2) 16. 5-0-Benzoyl-3-C-carbonethoxymethyl-3-deoxy-1,2-0 isopropylidene-β-L-lyxofuranose (Type VIII).

Clear syrup that shows up as a single spot on silica gel thin layer chromatography moving (detected with UV light and iodine vapors).

I R. CHCl 1 mm beam path v max 1730 (wide, C = O) cm N.M.R. in CDCl3 # 5.85 (d, J1,2 = 4Hz, H-1) 64.75 (t, J2,1 = 4Hz, -H-2) # 4.08 (m, -CH2-CH3, J = 7 , 0 Hz) # 1.60; 1.32 (2s, C (CH3) 2) # 1.20 (t, J = 7.0 Hz, -CH2CH3) 17. 5-O-Benzoyl-3-C- (carboxymethyl-2,3-γ- lactone) -3-deoxy-L-lyxofuranose (Type IX).

Fine white needles made of CHCl3 / petroleum ether, boiling point 60 to 80 ° C, Melting point 111 to 112 ° C.

I. R. CHCl3 lmm beam path # max 3450 (wide, OH). cm1 1785 (c = O lactone ) cm 1725 (C = O ester) cm 1 N.M.R. in CDCl3 # 5.55 (s, H-1) 64.94- (d, J2.3 = 7.0 Hz, H-2) 18. 5-O-Benzoyl-3-C-carboethoxymethyl-3-deoxy-1,2-O-isopropylidene-α-D-glycero-pent-2-enofuranose (Type VII).

Manufactured as an oil that shows up as a single stain on silica gel thin layer chromatography moving (proven with iodine vapors).

I.R. CHCl3, 1 mm beam path, 1750 (wide C = O) em 1610 (C = C) cm a Process for the production of a prostaglandin (P) as defined above from an intermediate of formula (II) is described in the following example.

a) (3R) -3- [carboxymethyl-3,4-γ-lactone] - (4R) -4-hydroxy- (2S) -2- [3'-oxo-trans-1'-octenyl] tetrahydrofuran (i) A mixture of 2.5 g of 1,4-anhydro-3-C- (carboxymethyl-2,3-ry-lactone) -3-deoxy-D-allitol (Formula II) and 2.84 g of sodium metaperiodate in 50 ml of 80% methanol was used for 15 minutes stirred at room temperature. After adding 50 ml of ether, the mixture was used for removal of the precipitated sodium iodate (NaIO3) filtered. The filtrate was reduced under The pressure was evaporated, the residue was taken up in 20 ml of ethyl acetate and dried over Na2S04 and filtered and the solvent removed under reduced pressure, a Oil was obtained. This oil was dissolved in 200 ml of dry benzene and in a Dean-Stark trap refluxed for 45 minutes. After removing the benzene 1.77 g of 1,4-anhydro-3-C- (carboxymethyl-2,3-γ-lactone) -3-deoxy-D-ribit-5-aldehyde were obtained under reduced pressure obtained as oil.

ç max.GHC13 1780 (C = O lactone) and 1740 (C = O aldehyde) cm 1. The compound was not further characterized, § was used immediately for the next reaction.

A solution of 1.92 g of dimethyl 2-oxoheptylphosphonate in 10 ml of dry DME was added at 0 ° C. to a suspension of 0.272 g of sodium hydride (60% dispersion in oil) in 65 ml of dry dimethoxyethane (DME) under nitrogen. The mixture was stirred for 30 minutes at room temperature, cooled to OOC and a solution of 1.06 g of the aldehyde prepared in the manner described above in 25 ml of dry DME was added. The mixture was stirred for an additional 2 hours at room temperature. After neutralization with acetic acid, the solution was filtered through "Celite" diatomaceous earth. The filtrate was evaporated to dryness under reduced pressure. The oil obtained was chromatographed on silica gel with ethyl acetate / n-hexane (1: 4 # 2: 3), whereby 1.39 g of a compound of the formula was obtained, which crystallized from ether / petroleum ether (40-60 ° C) as platelets with a melting point of 65 to 67 ° C [α] D22 + 34 ° (C 0.9 CHCl3).

I.R. Spectrum #max. CHCl3, 1790 (C = O lactone), 1680 (C = O) and 1640 (CH = CH) cm 1 Analysis: Found: C 66.60 H 7.91. Calculated for C14H20O4: C 66.67 H 7.99 N.M.R. in 'CDC13: # 0.87 (3H, t J = 7.0 Hz, CH2-CH3) 61.2-1.74 (6H, m, - (CH2) 3-) # 2.54-3.02 (3H, m, H-3 and -CH2-CO-) # 3.94-4.23 (2H, m, H-5 (a + ß)) # 4.32 ( 1H, t, H-2, H2,3 = J2,1 = 5Hz) 65.08 (1H, m, H-2) 0 # 2.52 (2H, t, J = 7 Hz-CH2-C-CH = CH-) # 6.30 (1H, dd, H-2 ', J1', 2 '= 15.75 Hz, J2.2' = 1.0 Hz) 66.66 (1H, dd, H-1 ', J1', 2 '= 15.75 Hz J2.1 '(= 5.0 Hz) b) (3R) -3- [carboxymethyl-3,4-γ-lactone] - (4R) -4-hydroxy- (2S) -2 - [(3'RS) -3'-hydroxy-trans-1 ' -octenyl] tetrahydrofuran (ii) To 1.95 g of sodium borohydride in 50 ml of dry dimethoxyethane, 3.4 g were fresh given molten ZnC12.

The mixture was stirred at 0-500 for 18 hours. After filtration the clear solution (about 0.5 molar) was used immediately under nitrogen.

To a solution of 252 mg of the compound (I) in 4 ml of anhydrous DME was added 1.0 ml of the zinc borohydride solution. The mixture was stirred at room temperature until reduction was complete (about 60 minutes), after which saturated potassium hydrogen tartrate was added dropwise until no further gas evolution was observed. After adding 25 ml of ethyl acetate, the solution was dried over sodium sulfate and filtered. The filtrate was evaporated to dryness to give a colorless oil. This oil was purified on a silica gel column with chloroform and chloroform / methanol (95: 5) to give 245 mg of an oil which crystallized on standing. Recrystallization from chloroform / petroleum ether (40-60 ° C.) gave a compound of the formula obtained in the form of platelets with a melting point of 94 to 970C. yes722 + 4 ° C (C 1.8 CHC13) or max OHO 13 3480 (OH) 1780 (C = O), 1610 (CH = CH) cm NMR in CDCl3: # 0.90 (3H, t, J = 6 , 0 Hz, -CH2-CH3) # 1.20-1.60 (8H, m, - (CH2) 4-) II 62.35-2.98 (3H, m, H-3 and -CH2CO-) OH ô 3.88-4.27 (4H, m, -CH-, H-5 (a + ß) and H-2 65.08 (1H, m, H-4) 5.74 (2H, m, - CH = CH-) c) (3R) -3-g-carboxymethyl-3,4ty-lactone-7- (4R) -4-hydroxy- (2S) -2 - [(3'RS) -3'-tetrahydropyranyloxy-trans -1'-octenyl] tetrahydrofuran (iii) of To a solution / 1.02 g (4017 mmol) of the compound (ii) in 10 ml of anhydrous dichloromethane was added a solution of 1.5 ml of toluenesulfonic acid monohydrate (TsOH) in tetrahydrofuran (50 mg TsOH / 10 ml THF) and 0.66 ml of dihydropyran were added. The mixture was stirred at room temperature for 30 minutes. The reaction was followed by thin layer chromatography. Then 15 drops of pyridine and then 40 ml of dichloromethane were added. The solution was washed with saturated sodium chloride solution, dried over Na 2 SO 4 and filtered. Evaporation of the solvent under reduced pressure gave an oil which was purified on a silica gel column with CHCl3e5% MeOH / CHCl3 to give 1.31 g of a compound (iii) in the form of an oil whose OH groups were blocked as tetrahydropyranyl ether became.

#Max. CHCl3 1780 (C = O) cm-1 and no -OH absorption d) (3R) -3- [formylmethyl-3,4-γ-lactol] - (4R) -4-hydroxy- (2S) -2- [(3'RS) -3'-tetrahydropyranyloxy-trans-1'-octenyl] tetrahydrofuran (iv) A solution of 1.20 g of compound (iii) in 10 ml of anhydrous toluene was cooled to -60 ° C under nitrogen. A solution of 5.8 ml of diisobutylaluminum hydride (20% strength solution in hexane) was added dropwise. The mixture was stirred at -60 ° C. for 20 minutes. Excess reagent was destroyed by the dropwise addition of methanol until the evolution of gas ceased. The mixture was then stirred for a further 15 minutes at room temperature. After adding 50 ml of ethyl acetate, the solution was dried over sodium sulfate and filtered. By evaporating the solvent under reduced pressure and purifying the residue on a silica gel column with chloroform # 5 Xsç; Methanol / chloroform, 1.15 g of oily lactol were obtained: max CHO13 3420 (-OH) and 1610 (CH = CH) cm -1 e) [8R, 12S] - (9R, 15S) -9,15-dihydroxy-11-oxa-prosta-cis-5: 6-trans -13: 14-dienoic acid (Va) A mixture of 0.96 g (24 mmol) of 60% sodium hydride in mineral oil and 10 ml of dimethyl sulfoxide (DMSO) was stirred for 45 minutes under nitrogen at 70 to 750C.

The resulting dark solution was cooled to 5 ° C. The solution became a solution of 5.88 g (12 mmol) of 4-carboxybutyl-triphenylphosphonium iodide in 10 ml of DMSO given.

The resulting dark red solution was 30 minutes at room temperature stirred and cooled to OOC. This solution became a solution of 1.36 g (4 mmol) of the lactol prepared in the previous stage in 2 ml of DMSO was added. The received The mixture was stirred at room temperature for 15 hours. The mixture turned to ice and Added water (200 ml) and the solution to remove neutral impurities extracted with petroleum ether (40 to 600C) and ether. The aqueous phase was with Oxalic acid acidified to pH 2 and extracted with ether (three times 50 ml).

The organic layer was washed with an aqueous sodium chloride solution, dried over sodium sulfate and filtered. Evaporation of the solvent under reduced pressure gave a crude product in the form of an oil, which was immediately hydrolyzed by stirring a solution of the oil in 10 ml of acetic acid / water (7: 3) for 4 hours at room temperature. Evaporation of the solvent under reduced pressure below 50 ° C. gave 1.82 g of an oil. This oil was chromatographed on plates for preparative thin layer chromatography with glacial acetic acid / ethyl acetate (2:98), 500 mg of the compound (V) in the form of an oil and 300 mg of the somewhat more polar compound (Va) in the form of an oil, which crystallized when left to stand were obtained. The compound (Va) was recrystallized from ether / petroleum ether (boiling point 40 to 60 ° C) at 4 ° C.

(V) RS-C-15-OH (Va) S-C-15-OH Analysis of the compound (Va): Found: C 67.0 H 9.4 Calculated for C19H32O5 'C 67.0 H 9.7 Melting point 66-67 ° C; [α] D26 + 59 ° (c 1,3 -CHCl3) # max CHCl3 3450 (OH) 1720 (C = O) and 1610 (CH = CH) cm -1 N.M.R. in CDCl3 60.89 (3H, t,. J = 6.0 Hz, CH2 - CH3) # 1.20-2.26 (15H, m, H-8 and CH2 of aliphatic chains) ô 2.33 (2 H, t, J = 7.0 Hz-CH2-CO2H) 63.77-4.22 (4H, m, H-9, H-10 (+ ß) and H-15) # 4.31 (1H, t, H-12, J8.9 = J12.3 = 4.0Hz) 64.3 (2H, m, H-5 and H-6) 65.68 (2H, m, H-13 and H-14) 65.20 (3H, (broad) OH and CO2H disappears on addition of -D20) -enantiomeric mixture (V) Analysis: Found: C 66.9 H 9.5 Calculated for C19H32O5: C 67.0 H 9.7 [α] D26 + 42 (c 1.4 CHCl3) v max CHCl3 3460 (OH), 1720 (C = O) and 1610 (CH = CH) cm-1 N.M.R. in CDCl3 60.89 (3H, t, J = 6.0 Hz, -CH2-CH3) 61.20-2.26 (15H, H-8 and CH2 of aliphatic chains) # 2.34 (2H, t, J = 7.0 Hz, -CH2-CO2H) 63.60-4.40. (5H, m, H-9, H-10 (α + B), H-12 and H-15) # 5.20 (broad singlet 3H, OH and CO2H disappears on addition of D2O) 65.46 (2H, m, H-5 and H-6).

# 5.69 (2H, m, H-13 and H-14).

Claims (1)

Patent claims 9. 1. Compounds of the formula in which the group B is in the α or β position and is a hydrocarbon radical in which the α carbon atom is activated by a blocked or unblocked functional group that makes it oxidizable. 2. Compounds according to claim 1, characterized in that the a-carbon atom can be oxidized to an aldehyde by the functional group. 5. Compounds according to claim 1 and 2, characterized in that B is a hydrocarbon radical which is substituted with one or more or unsubstituted hydroxyl groups, at least one of which is on the a-carbon atom is substituted. 4. Compounds according to claim 1, characterized in that the group B is a group of the formula R OCH - and R3OCH2 CH -R40, in which R2, R; and R4 that can be the same or different, each represent a blocking group or R; and R4 together form part of a cyclic carbonate. 5. 5,6-Di-O-acyl -) - C- (carboxymethyl-2,3-T-lactone) -3-deoxy-D-gulofuranose 6. 5,6-Di-O-acyl-3-C - (carboxymethyl-2,3-y-lactone) -3-deoxy-D-allofuranose 7. 5-0-acyl-3-C- (carboxymethyl-2,3-y-lactone) -3-deoxy-D- ribofuranose 8. 5-0-acyl-3-C- (carboxymethyl-2,3-y-lactone) -3-deoxyl-L-lyxofuranose 9. 3-C- (carboxymethyl-2,3-8-lactone) -3-deoxy-D-gulofuranose-5,6-carbonate 10. 3-C- (carboxymethyl-2, -lactone) -3-deoxy-D-allofuranose-5,6-carbonate 11. 3-C- (carboxymethyl 2,3-8-lactone) -3-deoxy-5-0-methylribofuranose 12. 3-C- (carboxymethyl-2,3-γ-lactone) -3-deoxy-5-O-methyl-L-lyxofuranose 13. Compounds of the formula wherein A is a group of the formula or is, B is a hydrocarbon radical in which the carbon atom is activated by a blocked or unblocked functional group and can thereby be oxidized, and R and R1, which are identical or different, each represent hydrogen or together with the oxygen atom form a removable group . 14. Compounds according to claim 15, characterized in that the a-carbon atom can be oxidized to an aldehyde by the functional group. 15. Compounds according to claim 13 and 14, characterized in that that B is a hydrocarbon radical substituted with one or more or unsubstituted hydroxyl groups, at least one of which is on the a-carbon atom is substituted. 16. Compounds according to claim 13 to 15, characterized in that B is a group of the formula R20CH2 - and where R2, R3 and R4, which are identical or different, each represent hydrogen or a blocking group, or R5 and R4 together form part of a cyclic carbonate. 17. 5,6-Di-O-acyl-3-C - (carboxymethyl-2,3-Y-lactone) -3-deoxy-D - gulit and its esters. 18. 5-O-acyl-3-C- (carboxymethyl-2,3-γ-lactone) -3-deoxy-L-lyxitol and its esters. 19. 3-C- (carboxymethyl-2,3-γ-lactone) -3-deoxy-D-gulit-5,6-carbonate and its esters. 20. 3-C- (carboxymethyl-2,3-γ-lactone) -3-deoxy-5-O-methyl-L-lyxitol and its esters. 21. 1,4-Anhydro-3-C- (carboxymethyl-2,3-Y-lactone) -) - deoxy-D-allitol and its esters. 22. 1,4-Anhydro-3-C- (carboxymethyl) -2,3-γ-lactone) -3-deoxy-D-ribitol and its esters. 23. Process for the preparation of compounds of the formula in which the group B can be in the α or β position and is a hydrocarbon radical in which the α carbon atom is activated by a blocked or unblocked functional group and can thereby be oxidized, the hydrocarbon radical having one or more substituted or unsubstituted hydroxyl groups, at least one of which is on the α-carbon atom; can be substituted, characterized in that compounds of the formula wherein 3 has the stated meaning, except that any blocking groups are acid-resistant, Y is a group of the formula R5 and R6, which are identical or different, are hydrogen or an alkyl radical or together form part of a carbocyclic ring having 4 to 6 carbon atoms, and Z is a hydrocarbon radical, treated with an aqueous acid to remove the group Y . 24. The method according to claim 23, characterized in that the compounds of the formula (XIV) are prepared by converting a) compounds of the formula (III) into a compound of the formula (IV) in which B and Y have the abovementioned meanings, converts b) the compounds of the formula (IV) to compounds of the formula in which B and Y have the abovementioned meanings, converts c) the compounds of the formula (V) into compounds of the formula in which B and Y have the abovementioned meanings and Z is a hydrocarbon radical, and d) selectively converts the compounds of the formula (VI) from the B side to compounds of the formula (XIV). 25. The method according to claim 23, characterized in that the compounds of the formula (XIV) in which B is in the a-position, prepared by a) compounds of the formula (III ') in compounds of the formula (IV') in which B and Y have the meanings given above, converted, t) the compounds of the formula (IV ') to compounds of the formula in which B and Y have the abovementioned meanings, oxidizes, c) the compounds of the formula (V ') in compounds of the formula converts, d) the compounds of the formula (VIa) to compounds of the formula isomerized, where B and Y in the formulas (VIa) and (VII) have the meanings given for the formula (IV '), and Z is a hydrocarbon radical, and e) the compounds of the formula (VII) are selective from the β side reduced to compounds of formula iIV) in which B is in the a-position.