IE42941B1 - Furo/3,4-6/furone derivatives and their preparation - Google Patents

Abstract

Compounds of the formula (I) in which the group B is in the alpha or beta position and is a hydrocarbon radical which is substituted by one or more free or protected hydroxyl groups, of which at least one is present on the alpha carbon atom, are prepared by treating compounds of the formula (II) in which the symbols Y and Z have the meaning stated in Claim 1, with an aqueous acid. The compounds of the formula (I) are valuable as intermediates for the synthesis of prostaglandins and prostaglandin analogues.

Description

This invention, relates to novel chemical compounds, processes for their preparation and their use as intermediates. The novel compounds are useful as intermediates in the synthesis of prostaglandins and prostaglandin analogues.

The novel compounds according to the invention are represented hy the following general formula: wherein B may be in the a- β-configuration and is a group 10 of formula R2OCH2— or RgOCHgCH— V in which Rg,. Rg and R^ are the same or different and each represents an alkyl, substituted alkyl or acyl group or, when B is ih the β-configuration and X is a hydrogen atom, a hydrogen atom, or Rg and R^ together form a carbonyl group; and X is a- or β-ΟΗ, or a hydrogen atom when B is in the β-configuration. ii η, Typical acyl croups represented by a9, £^ and are benzoyl and acetyl; and typical alkyl or substituted alkyl groups represented by R^, R, and R^ contain up to 4 carbon atoms in the aikyl moiety thereof, for example, trityl, benzyl or methyl.

Preferred compounds of formula I w.ien X is a- or β-ΟΗ include: ,6-di-O-acyl-3-C-(carboxymethyl-2,3-γ-lactone,-3deoxv-D-guiofuranose; , 6-di-O-acyl-3-C-(carboxymethyl-2,3—f-lactone) -3deoxy-D-allofuranose; -O-acyl -3 -C- (carboxymethyl -2,3 -γ -lactone) -3 -deoxyD-ribofuranose; -O-acyl-3-C- (carboxymethyl-2, 3-γ-lactone) -3-deoxy15 L-iyxofuranose; 3-C-(carboxymethyl-2,3-γ-lactone)-3-deoxy-Dgulofuranose 5,6-carbonate; 3-C-(carboxymethyl-2,3-γ-lactone>-3-deoxy-D-allofuranose 5,6-carbonate; 3-C-(carboxymethyl-2,3-γ-lactone)-3-deoxy-5-0methylribofuranose; and 3-c-(carboxymethyl-2,3-γ-lactone)-3-deoxy-5-0methyl-L_-lyxo£uranose.

Preferred compounds of particular preference of 25 formula I when X is H are:1.4- anhydro-3-C-(carboxymethyl-2,3-γ-lactone )-3deoxy-D-allitoi; and 1.4- anhydro-3-C-(carboxymethyl)-2,3-γ-lactone)-3deoxy-D-ribitol.

Compounds of the formula I are useful as intermediates in the preparation of prostaglandins and prostaglandin analogues. The appropriate side chains may be added to - 4 the ring closed compounds by oxidation of the B group to an aldehyde followed by coupling of a first side chain and reduction of the lactone ring followed by coupling of a second side chain. These reactions may take place in the reverse order. A most important feature of the particular intermediates of the invention is that the stereochemistry at carbon atoms C^, C3 and CA is such as to produce prostaglandins and prostaglandin analogues of natural configuration when the side chains are added. It is these prosta10 glandins which exhibit biological activity.

In particular, the intermediates of the invention are useful in the preparation of a novel class of prostaglandins which show:activity as inhibitors of acid production by gastric mucosa and in the constriction or dilation of smooth muscle. These compounds form the subject of British Patent Application No. 17811/76 and may be represented by the following formula:- wherein A represents -C=0 or a-C---OH I I B represents Rg-C OH or Rg-C-oOH S_ represents H, lower alkvl or substituted lower 5 alkyl Z represents CH^-Cn^ or C=C in the cis configuration Rr and R_, the same or different, represent H or Of substituted or unsubstituted lower alkyl; W is -S-, -0- or -CH2Y is -S-, -0- or -CR^R, ^R,, R.- and R,,, the same or different, S t> _O ii represent H, substituted or unsubstituted lower alkyl or halogen; the tetrahydrofuran ring may be substituted at the position C 10 with a hydroxy or substituted hydroxy function and widen so substituted may form a cyclic acetal group with a a-hydroxy substituent; and esters thereof.

IS Compounds of the general formula I may be prepared by the stereospecific route described diagrammatically in the attached scheme. The significance of this route is that the starting materials are sugars of known, absolute configuration and each step is stereospecific.

Consequently, the absolute stereochemistry of the compounds I is known. This, as mentioned above, is important in prostaglandin production in which the stereochemical relationship of groups is important.

In the accompanying drawing, B of formula III is as in formula I whereas 3 in formulae IV->VII1 and XI is as in formula I, except that R^ and may also form part of an acetal ring.

Referring to the drawing: (a) Compounds of type III such as D-glucose, D-xylose and L-arabinose, whose absolute stereochemical configuration is known are converted by known methods into compounds of formula IV wherein Y is a group of the formula - 6 42941 and Rg and Rg, the same or different, are alkyl, preferably lower alkyl, hydrogen or a carbocyclic group of 4-6 carbon atoms. In particular Y may be isopropylidene or cyclo5 hexylidene. (b) Compounds IV are oxidized to compounds V for example using either ruthenium tetroxide (Lawton, Β. T. Szarch, W. A. and Jones, J.K.N., (Carbohydrate Research 10, 456-458, 1969) or dimethyl sulphoxide and an anhydride LO such as (0uodera» K, Hirano, S and Kashimura N.

Carbohydrate Research 6_ 276-285, 1968) or acetic anhydride (Sowa, W. Can. J. Chem., 46, 1586, 1968). (c) Depending on the configuration, compounds V are converted to compounds Via or VIb, wherein Z represents a L5 hydrocarbyl group, by, for example, a Wittig reaction which involves condensation with a phosphonate ylid (Rosenthal, A and Nguyen, L. Benzing. J. Org. Chem. 34 1029, 1969). Compounds Via have the B group in the β-position and compounds VIb have the B group in the a-position. (d) Compounds Via are isomerized by the use of a suitable base, such as DBN (1,5-diazabicyclo-{4,3,θ}-ηοη5-ene in dry non-hydroxylic solvent, such as benzene to give the novel compounds VII. (e) Compounds VII are reduced stereospecifically by methods known to the art, such as by catalytic reduction using, for example, palladium black in an ether or RanevNickel in an alcohol to give compounds of type VIII. (f) Compounds VIb may be converted directly into compounds VIII by stereospecific reduction by methods known in the art.

If VIII contains blocking groups R^, Rg and R,, which are acid labile they are selectively removed and replaced by acid stable groups, for example alkylidene to diacyl. (g) Compounds VIII are converted to compounds IX by removal of the blocking group Y by the use of aqueous acid e.g. acetic acid/water cr SCl/aqueous dioxane to give novel compounds of type IX. (h) Compounds of formula Via are converted to XI by stereospecific reduction, for example using a catalyst such as palladium on carbon (Rosenthal, A and Nguyen, L. Benziag J. Org. Chem. 34, 1029, 1969) or Raney-Nickel in an alcohol Compounds of type VIII may occur as a by product of this reaction sequence.

If XI contains blocking groups Rj, Rg and R^ which are acid hydrolysable, then they are selectively removed and replaced by acid stable groups, for example, alkylidene to diacyl. (i) Compounds XI are converted to compounds XII by removal of the blocking group Y with aqueous acid to give novel compounds XII. Compounds XII may be converted into compounds X by reaction w ith a suitable haloaoid in a solvent such as a dry acid or dry non-hydroxy solvent optionally containing an acid chloride; or by anhydride treatment followed either by reduction of the halo substituted intermediate with a suitable catalyst, such as 10% palladium on carbon in the presence of hydrogen and a nitrogenous base, such as a trialkylamine; or by reaction with the salt of an alkyl or aryl mercaptan to give the corresponding mercapto-intermediate followed by desulfurization, for example with Raney-Nickel, or by acylation of - 8 39 4 2· the hydroxy group and treatment with an alkyl or aryl mercaptan in the presence of a Lewis acid such as BFgetherate to give the corresponding mercapto-intermediate followed by desulfurization, for example, with RaneyNickel. (j) Compounds X and XII are a sub-group Within the group of compounds of formula I. B in compounds X and XII has the same meaning as in formula I.

The novel compounds and the processes for their preparation are further illustrated in the Examples 1 to 15 that follow in which parts by weight (w) and parts by volume (v) bear the same relationship as the kilogram to the litre. Example 16, illustrates the use of the novel compounds to prepare 11-oxoprostaglandins.

Example 1 Preparation of l,2:5,6-di-0-isopropylidene-ei-D-glucofuranose (compound of type IV) Anhydrous D-glucose (600w), dry acetone (4000v), anhydrous pulverized zinc chloride (480w), 89% orthophosphorio acid (30v) and anhydrous copper sulphate (lOOw) were mechanically stirred for 30 hours at room temperature. Undissolved glucose was filtered and washed with acetone. .The filtrate was cooled to 0°-5°C, made alkaline with sodium hydroxide (340w in 34OW water) and filtered. The filtrate was evaporated under reduced pressure to remove solvent, the residue diluted with v/ater and extracted with chloroform. The combined chloroform 2 Ο - 9 extract was washed with water, concentrated, dried and evaporated to give crude product (462w, 91% on recovered glucose), white crystals, mp 95-101°C. Recrystallisation from hexane/chloroform (2:1) afforded 1,2: 5,6-di-05 isopropylidene-ra-D-glucofuranose, mp 1O5-1C9°C.

Example 2 Preparation of I,2:5,6-di-O-isopropylidene-G-E-ribohexofuranos-3-ulose (type V) using ruthenium dio:iics 1,2:5,6-di-O-isopropylidene-a-D-glucofuranose (80w) v/as dissolved in 500v warm carbon tetrachloride. Saturated sodium bicarbonate solution (lOOv) was added at room temperature to give a two phase mixture. Ruthenium dioxide (Iw) was dissolved in lOOv 10% sodium metaperiodate and the resulting ruthenium fcofcroxido extracted into carbon tetra·· chloride. The extract was added to tha well stirred two phase mixture. Whenever the solution turned black, a 10% aqueous sodium metaperiodate solution was added until a yellow-green colour appeared. The reaction was followed by thin layer chromatography on silica gel using hexane/ ethyl acetate (3:2). When the reaction was complete, isopropyl alcohol (lOv) was added and the mixture filtered through celite. The carbon tetrachloride layer was washed with aqueous sodium thiosulphate and evaporated under reduced pressure to give the hydrate of the ketone.

Distillation of the hydrate at 120°C bath temp, 0.1 mm Kg vacuum gave 1,2:5,6-di-O-isopropylidene-a-D-ribohexofuranos-3-ulose. (78% yield) I.R. (CKC1-) 1 mm light -1 J path,v max 1770 cm (C=0), Example 3 Preparation of l,2:5,6-di-0-isopropylidene-a-D-ribohexafuranos-3-uiose (type V) using dimethyl sulphoxide and acetic anhydride 2941 - 10 30 A v;ell shaken mixture of 1,2:5,6-di-0.~i sopropyl i. dene α-D-glucofuranose (26w) in dimethyl sulphoxide (150v) and acetic anhydride (lOOv) was left for 48 hours at room temperature. Solvents were removed by distillation in vacuo and the residue distilled at 0.1 mm Hg at a bath temperature of 120°C to give an oil (21w). I.R. (CHCl ) -1 3 mm light path v max 1770 cm (C=0). Sowa, Vi. Can. J. Chem. 46, 1586, 1968.

Example 4 Preparation of 3-C-Carboethoxymethylene-3-deoxy-l,2:5,6di-O-isopropylidene-oj-D-ribo-hexofuranose (type Via) A solution of triethylphosphonoacetate (53, 8w), potassium t-butoxide (12w) in anhydrous dimethylformamide (150v) at 0°C was added to a solution of 1,2:5,6-di-015 isopropylidene-a-D-ribohexofuranos-3-ulose (42w) in dry dimethylformamide (15Ov) by positive N2 pressure. The mixture was stirred thoroughly at 0°C under for one hour and then at room temperature for 48 hours. The solvent was removed in vacuo and hexane added to the residue. After filtration the filtrate was evaporated to dryness under reduced pressure and the semi-crystalline solid purified by chromatography on silica gel using hexane/ethyl acetate initially in the proportion 4:1 (v/v) followed by 3:2 (v/v). A crystalline product (36w) resulted which was recrystallized from petroleum ether bp 4O-6O°C mp 71-72°C (needles).

N.M.R. in CDClgS 56.34 (q, C-l'H, J112=l,25Hz and σχ 4=2,0 Hz)? 5 5,84 (d, H-l, 2=4,O Ha) 55,72 (two t, H-2, J2 ^=4,0 Hz and J2 χ1=1,25 Hz: 54,66 (m, H-4) 54,05 (m, H-5 and H-6) 54,23 (q, -CH2-CH3, J = 7,0 Hz) £ SC - 11 ΰ 1,30 (t -CH,.-CH,, J = 7,0 Hz; d J 51,36? 51,44 and 51,50 (4s, C(CH^)„) Z IR CCl^ 1 mm light path, υ max 17.,0 (C=0 ester) cm 1660 (C=C) cm-1 Analysis Found c 58,47 H 7,31 C,,1-/.0., requires C 58,52 H 7,36 16 24 7 Example 5 Preparation of 3-C-Carboethoxymethyl-3-decxy~l,2s5,6-di-010 i sooropylidene-g-D-erythro-hex-3-enofurano ss (type VXXnovel compounds) 3-C.-Carboethoxymefchylene-3-deoxy-l,2:5,6-di-O-isopropylidene-g-D-ribo-hexofuranose (IOw) was dissolved in dry 'benzene (5v) and 1,5-diazabicyclo-^4.3.0}-non-5-ene (QBN) (3.73w) was added and the mixture stirred at room temperature (26°C) under nitrogen for 48 hours. The reaction was followed by thin layer chromatography using silica gel and hexane/ethyl acetate 3:2 (v/v). The disappearance of starting material can be followed by spraying the plate with 9.5% chromic acid in 80% sulphuric acid solution followed by heat. On completion of the reaction the solvent was removed under reduced pressure and the product purified by column chromatography using silica gel and hexane/ethyl acetate 3:2 (v/v) to afford the pure product as a pale yellow oil (7,4w).

N.M.R. in CDC13: 55,99 (d, J6Hz, IH); 55,31 (d, uSKz, IH); 54,71 (t, J7Hz, IH)? 54, 3,91 (m, 4H); 53,43-3,19 (q, J17HZ, 2H) ? 51,43 (s, 9H)f 5 1,36 (s, 3H)? 5 1,26 (t, J7Hz, 3H) I.R. CHCl3, 1 mm light path, v max 1735 (C=0, aster) 438 44 - 12 'Example 6 Preparation of 3-C-carboethoxymethyl-3-deoxy-l,2:5,6-di-0isopropylidene-a-D-gulofuranose (type VIII-novel compounds) Freshly prepared 3-C-carboethoxymethyl-3-deoxy-l»2: i 5,6-di-0-isopropylidene-a-D-erythro-hex-3-enofurano se (O.lw) in dry ether (5v) was added to palladium black (0.2w) and 2 the mixture shaken under at a pressure of 1,2 kp/cm for .5 hours. The mixture was filtered and evaporation afforded a crystalline product (0,09w) mp. 80-82°C (needles) .0 N.M.R. in CDClgS 55,81 (d, H-l, 2 = 4,0 Hz) 54,70 (t, H-2, J2 3 = 4,0 Hz) X.R.: CHCl^ 1 mm light path, υ max 1735 (C=0 ester) cm b Analysis Found: C 58,32 H 7,86 .5 C1gH2g0^ requires C 58,17 H 7,93 Example 7 Preparation of 3-C-carboethoxymethyl-3-deoxy-l,2-0isopropylidene-a-D-gulofuranose (type VIII) 3-C.-Carboethoxymethyl-3-deoxy-l,2:5,6-di-O-isopropyl0 idene-a-D-gulo£uranose (Iv?) in acetic acid/water 3:2 (v/v) was stirred in an open flask for 30 minutes at 70°C. The mixture was cooled to 0°C and neutralized with potassium carbonate (3,45w). Acetone (30v) was added and the mixture filtered. The residue was washed with acetone and the combined filtrate was evaporated to dryness. The residue was purified by column chromatography on silica gel using chloroform initially followed by 5% methanol/chloroform (v/v) to. afford 3-C-carboethoxymethyl-3-deoxy-1,2-isopropylidene-a-D-gulofuranose (0,2w) as an oil.

N.M.R. in CDC13 65,83 (d, J 2 = 4Hz, H-l) 54,76 (t, J1>2 = 4Hz, H-2) 63,04 (s, OK) 64,15 (q, J = 8Hz, -CH.CH.) —2 ύ 61,26 (t, σ = 8Hz, -CH ch3) CHCl. -V cm 1 mm light path v max. 3450 (-0H) 1720 (~C=0) cm-1 Example 8 Preparation of 5,6-di-0-acetyl-3-C-earboefeho2qzmethyi~3deoxy-1,2-0-isopropylidene-a-D-gulofuranoss (type VIII) Acetic anhydride (O.74w) and pyridine (G,6w) was added to 3-C-carboethoxyiaethyl-3-deoxy-I,2-isopropyIidenecs-D-guIofuranose (Iw) in chloroform (lOv). The mixture was stirred for 36 hours at room temperature (26°C). The mixture was diluted with ice-cold 5% hydrochloric acid and the chloroform solution washed with the acid solution to remove all traces of pyridine. The chloroform solution was washed with saturated aqueous sodium bicarbonate then water, and dried over anhydrous sodium sulphate. Removal of the chloroform under reduced pressure gave 5,6-di-Oacetyl-3-C-carboethoxymethyl-3-deoxy-1,2-0-isopropylidensα-D-gulofuranose (O,98w).

IR. CHCi^ 1 mm light path vmax 1730 cm (C=0, broad) Example 9 Preparation of 5,6-di-0-aeetyl-3-c-(carboxymethyI)-2,3-γlactone)-3-deoxy-D-gulofuranose (type IX) ,6-di-0-acetyl-3-C-carboethoxymethyl-3-deoxy-l,2-0isopropylidene-cs-D-gulofuranose (Iw) was dissolved in acetic acid/water (20v) 4:1 (v/v) and stirred at SO°C for 6 hours. The solvent was removed under vacuum and the residual water removed as a benzene azeotrope. The 2 9 4 4 - 14- product was purified by column chromatography on silica gel using 2% methanol/chloroform (v/v) to give a crystalline product (0,53w) Mp. 118-12O°C.

I.R.s CHCl^ 1 a™ light path V max 3450 (-0H) cm-1 1810 (lactone) cm-'' 1725 (C=0 ester) cm Example 10 Preparation of 3-C-carboethoxymethyl-3-deoxy-1,2:5,6-di-010 isopropylidene-a-D-allofuranose (type XI) A solution of triethylphosphonoacetate (55w), potassium t-butoxide (15,8w) in anhydrous dimethylformamide (75v) at 0°C was added to a solution of 1,2:5,6-di-0-isopropylidene-α-D-ribohexofurano s-3-ulo se (36.8w) in dry dimethyl15 formamide (75v) by positive Big pressure. The mixture was stirred thoroughly at 0°C tinder nitrogen for one hour and then at room temperature for 48 hours. The solvent was removed in vacuo and the residue extracted with dry hexane (4 x lOOv). The combined hexane extract was filtered and evaporated to give a syrup which crystallized on standing. Raney-Nickel (30w) in methanol (lOOv) was added and the mixture shaken under Hg (2 atmospheres pressure) at room temperature for 3.5 hours. Filtration and evaporation of the solvent gave a syrup which was purified by column chromatography using silica gel and chloroform as eluant. The product obtained from the column was recrystallized from cyclohexane to give crystalline 3-C-carboethoxymethyl3-deoxy-l,2:5,6-di-O-isopropylidene-a-D-allofuranose (33,4w) mp 90-91°C (needles).

N.M.R. in CDClgj 65,75 (d, H-l, σχ g = 4,0 Hz) 4,78 (t, H-2, Jg'g = 4,0 Hz) 3S 4 - 15 30 52,32 (m, H-3? 54,14 (q, -CB2-CH3, J = 7,0 Ha) 51,26 (t, -CH -CH„, J = 7,0 Hz) Δ -J Si,29? 51,31; 51,39 and 1,48 i4s, C(CHn)„} *· o 2 I.R. : CCl. 1 mm light path, vmax 7730 (C=0 ester) -1 4 cm Analysis Found : C 58,33 H 7,88 C.,Η.^0- requires C 58,17 H 7,93 2q / In larger scale preparations crystalline 3-C-carbo10 athoxymethyI-3-deoxy-l,2:5,S-di-O-isopropylidene-a-Dgulofuranose was isolated from the column chromatography described above. The compound was purified by recrystallization from petroleum ether (bp 4O-6O°C), mp 80-32°C.

Example 11 Preparation of 5,6-di-C-acetyi-3-C-carboethoxymethyl--3deoxy-1,2-0-isopropylidene-a-D-allofuranose (type XI) 3-C-carboethoxymethyl-3-deoxy-l,2:5,6-di-0-isopropylidene-ot-D-allofuranose (33,4w) in acetic acid/water 4:1 (v/v) (100v) was heated at 70° C for 40 minutes. The mixture was cooled in an ice bath and potassium carbonate (160w) was added in portions. Acetone (500v) was added and the mixture filtered through a celite pad and the fixtrate evaporated. The residue was dissolved in chloroform (250v) and filtered. Evaporation of the filtrate afforded a syrup which was purified by column chromatography using silica gel as stationary phase and first chloroform then chloroform/methanol (97.5:2.5) (v/v) as eluant to give pure 3-C-carboethoxymethyl-3-deoxy-l,2-0-isopropylidene-a-Dallofuranose, (22,4w), colourless oil.

I.R. CHC13 1 mm light path, vmax 3500 (OH) cm-1; - 16 1735 (C=0 ester) cm 3-C-carboethoxymethyl-3-deoxy-l,2-0-isopropylidene-aD-allofuranOse (88w) in dry chloroform (50v) was added to dry pyridine (52,7w) in acetic anhydride (68,2w). The mixture was left at room temperature for 28 hours. Chloroform (300v) was added and the mixture extracted first with water, then with 5% hydrochloric acid followed by 5% aqueous sodium bicarbonate. The chloroform layer was dried over anhydrous sodium sulphate filtered and evaporated under .0 reduced pressure to dryness to give a syrup. Purification of the syrups by column chromatography using silica gel and hexane/ethyl acetate (4:1) (v/v) afforded crystalline 5,6di-O-acetyl-3-C-earboethoxymethyl-3-deoxy-1,2-O-isopropylidene-a-D-allofuranose (88 w) after recrystallisation from .5 petroleum ether bp 40-60°C, mp 53-54°C. (needles).

R. in CDC1: 55,79 (a. H-l, Jl,2 = 3,7 Hz) 55,08 (m. H-5) 54,78 (t.H2' J2„3 = 4,0 Hz) 54,14 (Φ ’CK2-CH3, J = 7,0 Hz) 54,04-4,50 (m, H-6 and H-6 1) 53,95 (dd, H-4, J3 4 - 10 Hz and J $ = 5,0 Hz) 52,2-2,9 (m, H-l' and H-3) .2,02 and 52,04 (2s, CH^-CO-) !5 51,48 and 1,30 {2s, C(CH3)2) 51,26 (t, J = 7,0 Hz) —3 I.R.s 1 mm light path, vmax 1740 (broad C=0 ester) cm Analysis Found : C 54,26 H 6,95 10 C17H26°9 requires C 54,53 H 7,00 ΙΟ Example 12 Preparation of 5, 6-di-0-acetyl-3-£-(carbcxymethyi-2,3-γlactone)-3-deoxy-D-allofuranose (type XII) ,6-ai-0-acetyl-3-C-carboethoxymethyl-3-deoxy-l,2-0isopiopylidene-ct-E-ullofuranose (36,2w) was dissolved in acetic acid/water 4:1 (v/v) (200v) and heated at 90°C for 3 hours. The solvent was distilled off in vacuo and the residual water removed as a benzene azeotrope. Purification of the residue by column chromatography on silica gel and first hexane/ethyl acetate 3:2 (v/v), followed by 1:1 (v/v) and 2:3 (v/v) as eluants afforded pure 5,6-di-Oacetyi-3-C-(carboxymethyl-2,3-γ-lactone)-3-deoxy-D-allofuranose as an oil (20w). 2C N.M.R. in CDCl '3: 65,56 (s, H-I) 65,18 (m, H-5) 64,88 (d, H-2,J2, . - 6.0 Hz) 3 54, 0—4 „56 (m, i H-4, H-6 and H-6'5 62,40- -3,24 r (m, H-I1 and H-3) 62,08 and 2,10 (2s , CHg-CO-) I.R. : CHC1 1 mm light path, vmax 3420 (OH) cm 1785 (0==0 lactone) cm and 1735 (C=0 ester) Treatment of 5,6-di-0-acetyl-3-C-(oarboxymethyl-2,3γ-lactone)-3-deoxy-D-allofuranose (0,lw) with acetic anhydride (IV) and pyridine (XV) gave after usual isolation crystalline, 1,5,6-tri-0-acetyl-3-o-(carboxymethyI-2,3-γlactone-3-deoxy-p-D-allo£uranose (0,08w), mp. 106-107 C (plates).

N.M.R. in CDCI δ 6,34 (s, H-l) 3' - 18 55,09 (m, H-5) δ4,93 (d, H-2, J„ = 6,0 Hz) Z / J 54,18 (dd, H-4, = 4,0 Hz and J3 4 = 8,5 Hz) 64,58-3,88 (m, H-6 and H-6') i 63,26-2,40 (m, H-l' and H-3) 62,04; 62,10 and 62,11 (3s, CH--C0-) I.R. : CHCl_: 1 nun light path, ymax 1785 (C=0 —1 —1 lactone) cm and 1750 (C=0 ester) cm Analysis Found : C 50,95 H 5,44 .0 01ΛΗ1θ09 requires C 50,93 H 5,49 Example 13 Preparation of 5,6-di-O-acetyl-1,4-anhydro-3-C-(carboxymethyl -2,3-γ-lactone)-3-deoxy-D-allitol (type X) via mercapto-intermediates .5 (a) 5,6-di-0-acetyl-3-C-(earboxymethyl-2,3-γlactone)-3-deoxy-D-allofuranose (7,2w), 4-nitrobenzoylchloride (5w), pyridine (2.2w) and dry chloroform (lOOv) were stirred at room temperature for 24 hours. Water (lOv) was then added and the mixture stirred for 0.5 hours. :0 The chloroform phase was washed with IN sulphuric acid, aqueous sodium bicarbonate and water, dried over anhydrous sodium sulphate and filtered. Evaporation of the solvent gave 5,6-di-0-acetyl-3-C-(carboxymethyl-2,3-γ-1actone)-3deoxy-l-O-p-nitrobenzoyl-D-allofuranose as a syrup (10,4w).

This compound was dissolved in dry dichloromethane (100 v), cooled to 0°C and dry HBr gas bubbled through for 0.75 hours. The flask was stoppered and kept at 4°C for 72 hours. The mixture was filtered to remove the p-nitrobenzoic acid formed and the filtrate evaporated in vacuo below 50°C. A solution of thiophenol (2,93 w) and potassium hydroxide (1,35 w) in ethanol (50v) was added to the residue and the mixture warmed on a waterbath (5O-6O°C) for d 2 ii 5 : minutes. Tha solvent was evaporated and the residue purified by column chromatography using silica gel and hexane/ethylacetate 3:2 (v/v) as eluant. The product obtained from the column (7,7 w) gave after recrystallizatior from chloroform-ether crystalline phenyl 5,6-di-Oacetyl-3-C-(carboxymethyl)-2,3-γ-lactone)-1,3-dideoxy-1thio-a-D-allofuranoside, mp. 113-115°C (needles) N.M.R, in CDCl : 67,2-7,56 (m, phenyl) 65,75 (d, H-l, 2 = 5,0 Hz) 65,20 (dd, H-2, J , = 5,0 Hz) and J , = 7,5 Hz . Irradiation of the H-l signal at 65,76 collapsed the H-2 signal to a doublet of J, 3 = 7,5 Hz) 65,18 (m, H-5) 64,52-4,0 (m, H-4, H-6 and H-6') 63,16-2,44 (m, H-l' and H-3) 52,04 and 2,08 (2s, CH -CO-) I.R. : CHCl, 1 mm light path, umax 1790 (C=0 J -1 -1 lactone) cm and 1745 (C=0 ester) cm Analysis Found : C 56,95, H 5,19 ^13^20^^7 requires C 56,83 H 5,30. (b) To a solution of 70 w, 1,5,6-tri-O-acetyl-3C-(carboxymethyl)-2,3-γ-lactone)-3-deoxy-p-D-allofuranose in 300 v dry benzene was added 10,5 v BF3-etherate and 27,5 w thiophenol and the mixture stirred at room temperature for 16 hr. Ether (500 v) was added and the mixture extracted with saturated sodium bicarbonate (2 x 100 v). The organic layer was dried over Na2S0^ and evaporated under reduced pressure. Crystallization of the residue from chloroform-ether gave 60 w of phenyl 5,6-di-0-accfcyl42941 - 20 3-0-(carboxymethyl-2,3-y-lactone)-1,3-dideoxy-l-thio-a-Dallofuranoside, m.p. 113-115°C, + 343 (c 1,2 CHCl^).

The mother liquor (10 w) gave after chromatography on silica gel with first hexane-ethyl acetate (4:1) followed by (3:2) and (1:1) as eluants a further 2 w of the 1-a-phenyl-thio compound and 6 w of the corresponding l-β isomer (yield: 84% overall). Ι-β-phenylthio isomer m.p. 82-3°C _ 173° (c 3,2CHC13) Analysis: C 56,7 H 5,1 Calc, for C^g^QSO? C 56,8 H 5,3 N.M.R. (CDC13 - 60 mHz) 55,6 (d, H-l, σχ 2«1 Hz) 65,01 (dd, H-2, J2 χs»l Hz and J2 3 = 6 Hz).

The thio-intermediate from (a) or (b) above, (7w) in ethanol (75v) containing Raney-nickel (35w) was refluxed for 2 hours. Filtration and evaporation of the solvent gave 5,6-di-0-acetyl-l,4-anhydro-3-C-(carboxymethyl-2,3-γlactone)-3-deoxy-D-allitol (4,5w). Purification by column chromatography on silica gel using first hexane/ethyl acetate 4:1 then 1:1 (v/v) afforded an oil (4w) .

N.M.R. in CDC13: 55,05 (m, H-2 and H-5) 54,52-3,92 (m, H-l and H-6) 53,85 (dd, H-4, J3 = 7,5 Hz and J4 5 = 5,5 Hz) 52,95-2,50 (m, H-l' and H-3) 2,05 and 62,07 (2s, CH..-C0-) I.R. s CHCl.. 1 mm light path, umax 1790 (C=0 J -1 -I lactone) cm and 1750 (C=0 ester) cm Analysis Found : C 52,63 H 5,94 C12H16°7 retIuires c 52,84 H 5,92 Example 14 1,4-Anhydro-3-C-(carhoxymethyl-2,3-γ-lactone)-3-deoxy-Dallitol (type X novel compounds) A mixture of 5,6-di-0-acetyl-l,4-anhydro-3-C-(carboxy5 methyl-2,3-y-lactone)-3-deoxy-D-allitol (4 w) and anhydrous potassium carbonate (4 w) in methanol/water 5:3 (v/v)(40v) was heated for 2 hours at 70°C. The solution was then acidified with Dowex 50 W resin to pH 3, and filtered. The filtrate was evaporated and residual water removed as a 1C benzene azeotrope to give a syrup which crystallized on standing. Recrystallization frcm methanol/diethyl ether or absolute ethanol/diethyl ether gave crystalline needles (2,5w), mp. 134-i3P°C.

Analysis Found : C 51,04 H 6,31 C8H12^5 re<5u^res c 51,05 H 6,45 Example 15 By similar methods the following compounds were prepared: 1. 1,2-0-Iscpropylidene-a-D-xylofuranose (type IV compound) from D-xylose (Levene, P.A., Raymond, A.L. J. Biol. Chem. 102., 317, 1933).

A colourless oil which slowly crystallized, m.p. 34-40°C. 2. 5-0-Benzoyl-l,2-0-isopropylidene-a-D-xylo25 furanose (type IV compound). (Levene, P.A., Raymond, A.L. J. Biol. Chem. 102, 317, 1933.

White needles from chloroform/hexane, m.p.

S3°C.

I.R. : CHCl1 mm light path vmax 3470 (-0H) ci»·1 1710 (-C=0) cm-1 1600 (-C=C-) cm-J· . 5-O-benzoyl-i, 2-0,-isopropylidene-a-Derythro-pentofuranos-3-ulose (type V compound) (Tong, G.L., Lee, W.W. and Goodman, L. J. Org. Chem. 32, 1984, 1967) White needles from ether/chloroform/hexane m.p. 94-95°C. 4. 5-O-benzoyl-3-C-carbomethoxymethyl-3-deoxyl, 2-0-isopropylidehe-a-D-ribofuranose (type XI compound-novel compound).

Fine white iieedles from chloroform/hexane m. p. 86-87°C.

I.R. : CHC13 1 mm light pathυmax 1720 (C=0) cm-1 1600 (-C=C-) cm1 ,M. ,R. in CDd. δ 5,86 (d, J. . = 4H , H-l);. 1,2 z δ 4,80 (t.J2,l = 4HZ’ H2); δ 3,66 (s. 0CH3); δ 1,50; 1, 31 (2s, C(CH3)2) Analysis Found s C 61,66 H 6,21 <18^22θ7 retIui^®s C 61,70 H 6,33 . 5-O-Benzoyl-3-C-(earboxymethyl-2,3-y-lactone)3-deoxy-D-ribofuranose (type XII compoundnovel compound). Fine white needles from acetone/petroleum ether bp 60-80°C. mp. 114-115°C.

I.R. : chloroform, 1 mm light path vmax 3400 (broad OH) cm 1 1790 (-0=0 lactone) cm 1720 (-0=0 ester) cm 1 1600 (-C=C-) cm 1 f P t «ϋ tJ/ - 23 H.K.R. in CDCl, 6 5, 60 (s, H-l) 64,91 (d, _ z, 3 = 6 Hz, H-2) Analysis Found : C 60,45 H 5,05ciA4°- requires c 60,43 H 5,07 6. 5-0-Benzoyl-3-C-(carboxymethyl-2,2-γ-lactone)3-deoxy-l-0-(p-nitrobenzoyl)-β-D-ribofuranose. Fine white needles from ethyl acetate/ petroleum ether bp 6O-8O°C, mp. 13O-132°C.

I.R. CHCl^ 1 mm light path Vmax 1800 (c=o lactone) cm 1735 (C—0 ester) cm b 1530 (no,) ι cm-1 N.M.R. in CDCl3 66,63 (s, H-l) 65,19 (d, J2 = 6 Hz, H-2) Analysis Found : C 58,68 H 3,98 C2iK,?NOg requires C 59,00 H 4,01 7. Phenyl 5-0-benzoyl-3-C-(carboxymethyl-2,3-γ~ lactone) I,3-dideoxy-l-thio-a-D-ribofuranoside. Fine white needles from ethyl acetate/hexane Mp. 129-13O°C.

I.R. : CHCl, 1 mm light path vmax 1795 (C=0 lactone) cm 1725 (C=0 ester) cm ~ N.M.R. in CDCl, 65,81 (d, 2 = 5 Hz, H-l) 65,23 (dd, 2 = 5 Hz, J2 3 = 7,5 Hz, Analysis Found : C 64,51 ίϊ 4,86 ^20^18^5^ re<3u4res c 54,85 H 4,S9 LO L5 iO - 24 8. 1,4-Anhydro-5-0-benzoyl-3-C-(carboxymethyl) 3-deoxy-D-ribitol (type X compound). Crystall ine needles from ethylacetate/petroleum ether bp. 60-80°C, mp. 13O-133°C.

I.R.: Chloroform, 1 mm light path υmax 1785 (C=0 lactone) cm 1725 (C=0 ester) cm N.M.R. in CDC13 δ 8,06-7,22 (m, phenyl) 55,03 (m, H-2) 4,54-3,90 (m, H-l, H-4, H-5) 53,00-2,44 (m, H-l', H-3) Analysis Found : C 64,31 H 5,38 C14H14°5 requires C 64,57 H 5,33 9. l,4-Anhydro-3-C-(carboxymethyl-2,3-y-lactone)3-deoxy-D-ribitol (type X compound).

Obtained as an oil which moved as a single spot on silica gel thin layer chromatography (detected with iodine vapour).

I.R.: CHCl, 1 mm light path -ymax 3490 (broad, OH) cm 1790 (C=0 lactone) cm . 5,6-di-0-Benzoyl-3-C-carbomethoxymethyl-3deoxy-l,2-0-isopropylidene-a-D-allofuranose (type XI compound). Crystals from methanol/ ether mp. 63-65°C (needles).

I.R.s CHCl 1 mm light path vmax - J -1 1730 (C=0 ester) cm 1600 (C=C) cm N.M.R. in CDC13 58,08- -7,2- 4 (m. phenyl) 55,83 (d, H-l,Jl,2 = * Hz) 54,79 (t. H-2,J2,3 = 5 Hz) 53, 55 (s. °ch3: ) Analysis Pound s C 64,14 H 5,71C26K28°9 requires C 64,48 H 5,82 II. 5,6-di-Ο-Benzoyl-3-C-(carboxymethyl-2,3-γlactone)-3-deoxy-D-allofuranose (type ΧΪΧ compound). Crystals from ether mp. 12310 124°C.

N.M.R. in CDC13 δ 5,62 (a, H-l) 4,92 (d, , = 6 Hz, H-2) I.R.: CHCl, 1 mm light path vmax ** J 1780 (C=0 lactone) cm 1730 (C=0 ester) cm 1600 (C=C) Analysis Found : C 64,15 H 4,86 C22H2O°8 re‘2ulres c 54,04 H 4,89 12. Phenyl 5,6-di-0-Benzoyl-3-C-(carboxymethyl2,3-γ-lactone)-1,3-dideoxy-l-thio-a-Dallofuranoside. Crystals from chloroform/ methanol, mp. 137-138°C (needles).

N.M.R. in CDC13 ¢5,82 (d, 2 = 5 Hz, H-l) 55,22 (dd, J = 7,5 Hz, σχ 2 = 5 Hz H-2) I.R.: CHCl. 1 mm light path vmax J _i 1790 (C=0 lactone) cm 1730 (C=0 ester) cm 1600 (C=C) - 26 13. 14.

. Analysis Found : C 66,24 H 4,63 C28H24S°7 retTuires c 66, 68 H 4,79 I, 4-Anhydr o-5, 6-di-0-benzoyl -3 (carboxymethyl2,3-y-lactone)-3-deoxy-D-allitol. (Type X). Crystals from chloroform/ether, mp. 126-127°C (needles).

N.M.R. in CDC13 54,87-4,43 (m, H-l) 55,11 (m, H-2) X.R. : CHCl. 1 mm light path vmax 1790 (C=0 lactone) cm 1730 (C=0 ester) cm Analysis Found : C 66,68 H 5,00 C22H2O°7 reSu-'-res c 66,65 H 5,09 -0-Benzoyl-1,2-0-isopropylidene-β-L-arabinofuranose (Type IV). Prepared as described (Ε. M. Acton, K. J. Ryan and L. Goodman, J. Am. Chem. Soc., 86, 5352 (1964); E. J.

Reist, P. A. Hart, L. Goodman and B. R. Baker ibid, 81, 5176 (1959). Fine white needles from benzene/petroleum ether bp 40-60°C, m.p. 146-147°C.

I.R.: CHCl 1 mm light path vmax 1725 -I3 (C=0) cm. . -0-Benzoyi-l,2-0-isopropylidene-p-L-threopentofuranos-3-ulose (Type V). Fine white needles from diethylether, mp. 85-87°C.

I.R.s CHCl, 1 mm light path vmax 3 -1 1727 (C=0 ester) cm 1780 (C=0 ketone) cm~ £ 2f.

N.M.R. in CDC13 ^6,05 (a, J 2 = 4 Hz, &'-> «1,50, 1,40 (2s, C(CH3)2) 16. 5-0-Benzoyl-3-C-carboethoxymethyl-3-deoxy5 1,2-0-isopropylidene-p-L-lyxofuranose (Type VIII) A clear syrup which moved as a single spot on silica gel thin layer chromatography detected with uv light and iodine vapour.

I.R.: CHC13 1 mm light path vmax 1730 (broad, C=0) cm ~ N.M.R. in CDC1„ 6 5,85 (d, X 2 = 4Hz, H-l) 6 4,75 (t. : = 4Hz, H-2) 6 4,08 (m. -CH2-CH3, J = 7,0 Hz) 61,60; 1 —1 32 (2s, C(CH3)2) 61,20 (t, J = 7,0 Hz, -CH2CH3) 17. 5-0-Benzoyl-3-C-(carhoxymethyl)-2,3-y-lactone)3-deoxy-L-lyxofuranose (Type IX). Fine white 0 needles from CHCl3/petroleum ether bp 60-80 C, mp. 111~112°C.

I.S.· CHCl 1 mm light path vmax 3450 (broad, OH) cm 1785 (C=0 lactone) cm 1725 (C=O ester) cm 1 N.M.R. in CDCl3 65,55 (s, H-l) 64,94 (d, J2 3 = 7,0 Hz, H-2) 18. 5-O-Benzoyl-3-C-carboethoxymethyl-3-deoxy30 1,2-O-isopropylidene-a-D~glyeero-pent-3429 41 ! - 28 enofuranose (Type VII). Obtained as an oil which moved as a single spot on silica gel thin layer chromatography (detected with iodine vapour).

I.R. CHC1_ 1 mm light path 1750 (braod C=0) cm 1610 (C=C) cm-1 The following Example illustrates a method of produc ing a prostaglandin (P) as hereinbefore defined from an intermediate of the formula II.

Example 16 (a) (25,3R,4R)-4-Hydroxy-2-{3'-oxo-trans-1'-octenyl} -3{Carboxymethyl-3,4-y-lactone}-tetrahydrofuran (i) A mixture of 1,4-anhydro-3-C-(carboxymethyl-2,3-γ5 lactone)-3-deoxy-D-allitol (2.5 g) (Formula I) and sodium metaperiodate (2.84 g) in 50 ml. 80% ethanol was stirred at room temperature for 15 minutes.

After the addition of ether (50 ml) the mixture was filtered to remove the precipitated sodium iodate (NalOg).

The filtrate was evaporated in vacuo, the residue taken up in 20 ml ethylacetate, dried over NagSO^, filtered and the solvent removed under reduced pressure to give an oil. This was dissolved in 200 ml dry benzene and refluxed in a Dean-Stark apparatus for 45 minutes. Removal of the benzene under reduced pressure gave 1.77 g l,4-anhydro-3C-{carboxymethyl-2,3-γ-lactone)-3-deoxy-D-ribitol-5aldehyde as an oil. umax CHC1. 1780 (C=0 lactone) and 1740 (C=0 aldehyde) cm . The compound was not further character0 ised but immediately used for the next reaction.

To a suspension of sodium hydride (0.272 g 60% dispersion in oil) in 65 ml dry 1,2-dimethoxyethane (DME) - 29 λ ir: c 4i Λα c under at 0°C was added a solution of 1.32 g dimethyl 2-oxoheptylphosphonate in 10 ml dry ΕΜΞ. The mixture was stirred at room temperature for 30 min, cooled to 0 C, a solution of 1.06 g of the aldehyde produced above in ml dry DME was added and the mixture stirred for a further 2 hr at room temperature. After neutralization with acetic acid the solution was filtered through celite and the filtrate evaporated to dryness under reduced pressure. The oil obtained was chromatographed on silica gel with ethyl acetate/n-hexane (Ii4-*2s3) to give 1.39 g of a compound which crystallized from diethyl ether-petroleum ether (40-60°C) as plates mp 65 -67°C + 34° (c 0,9 CHCl^) I.R. Spectrum vmax CKCl, 1790 (C=0 lactone) 1680 J -1 (C=0) and 1640 (CH=CH) cm C14H2O°4 ret3;’ires C 66,67 H 7,99 Found : C 66,60 H 7,91 N.M.R. in CDC13 0,87 (3H, t J = 7,0 Hz, CH,-CH„) 1,2-1,74 (6H, m, -(CH^-) II 2,54-3,02 (3H, m, H-3 and -CH2-C-O-) 53,94-4,23 (2H, m, H-5 (α+β)) δ 4,32 (IH, t. H-2, δ 5,08 (IH, m, H-2) 62,52 (2H, t. J= 7 δ6,3Ο (IH, dd. H-2J2, 2' = 1'° Hz) δ 6/ 66 (IH, dd, H-lJ2, χ, = 5,0 ' Hz) 2.3 = J. 2.1' = 5 Hz) Β HZ -CH2-C-CH=CH-) / J j. ι 2 i ~ 15,75 Hz, , Jl' 2* = 15'75 112 (b) {2 S,3R,3'RS,4R)-4-hydroxy-(2S) -2-{(3 'RS) -3 1 hydroxy-trans-11-octenyl}-3-{carboxymethyl3,4-γ-lactone} -tetrahydrofuran (ii) To sodium borohydride (1.95 g) in dry 1,2-dimethoxyethane (50 ml) was added recently fused ZnCl2 (3.4 g).

The mixture was stirred for 18 hr at 0-5°C. After filtration under nitrogen, the clear solution (ca 0,5 M) was used immediately.

To 252 mg (i) dissolved in anhydrous DME (4 ml) was added 1.0 ml of the zinc borohydride solution. The mixture was stirred at room temperature until the reduction was complete (about 60 min) saturated potassium hydrogen tartrate was added dropwise until no further evolution of gas was observed. Ethyl acetate (25 ml) was then added, the solution was dried over sodium sulphate, filtered and the filtrate evaporated to dryness to give a colourless oil This was purified on a silica gel column with chloroform and chloroform/methanol (95:5) to give an oil (245 mg) which crystallized upon standing. Reerystallization from chloroform-petroleum ether (40-60°) gave a compound $ OH as plates, mp 94-37 C, α + 4 C (C 1,8 CHCl ) v rns:’:D -1 J CHCl, 3480 (OH) 1780 (C=0), 1510 (CH=CH) cm j N.M.R. in CDCl s 50,90 (3H, t, J = 6,0 Hz, -CH^-CELj 51,20-1,60 (SH, m, -(CHO) -) II 52,35-2,98 (3H, m, H-3 and -Cf^CO-) OH I 53,88-4,27 (4H, m, -CH-, H-5 (α+β) and H-2 55,08 (IH, m, H-4) δ5,74 (2H, m, -CH=CH-) (c) (2S,3R, 3'R,4R)-4-hydroxy-2-{3'-tetrahydropyranyloxy -trans-1 '-octenyl}-3-{Carboxymethyl-3,4-γlactone)-tetrahydrofuran (iii) To a solution of 1.02 g (4,017 mmoles) (ii) in 15 anhydrous dichloromethane (10 ml) was added a solution of 1,5 ml toluenesulphonic acid monohydrate (TSOH) in THF (50 mg Ts0H/10 ml THF) and 0.66 ml dihydropyran. The mixture was stirred at room temperature for 30 min. and the reaction was followed by thin layer chromatography (tic) . Pyridine (15 drops) was added and then dichloromethane (40 ml). The solution was washed with a saturated sodium chloride solution, dried over Ka^SO^ and filtered. Evaporation of the solvent under reduced pressure gave an oil which was purified on a silica gel column with CHCl^—>5% MeOH/CHCl^ to yield 1.31 g of a compound (iii) as an oil with the OH blocked as the tetrahydropyranyl ether vmax CHClg 1780 (C=0) cm 1 and no -OH absorption. (d) (2S, 3R, 3'RS, 4R)-4—hydroxy-2-{31-tetrahydroxypyranyloxy-trans-1'-octenyl}-3-{PormyImethyl-3,4-γ -lactol}-tetrahydrofuran (iv) ) A solution of 1.20 g of (iii) in anhydrous toluene (10 ml) under nitrogen was cooled to -60°C. A solution of 5.8 ml diisobutylaluminlum hydride (20% soln, in hexane) was added dropwise. The mixture was stirred for 20 minutes at -60°C. Excess reagent was destroyed by the > dropwise addition of methanol until the evolution Of gas ceased. Stirring was continued for an additional 15 minutes at room temperature. Ethyl acetate (50 ml) was added,, the solution was dried over sodium sulphate ahd filtered. Evaporation of the solvent under reduced ) pressure and purification of the residue on a silica gel column with chloroform—>5% methanol/chloroform gave 1.15 g of oily lactol: OTHP vmax CHCl, 3420 (OH) and 1610 (CH=CH) cm (e) (8R, 9R, 12£>, 155)-9,lo-Dihydrcxy-ll-oxa-prostaais-5-trans-13-dienoic acid (va) A mixture of 0.96 g (24 mmole) of 60% sodium hydride in mineral oil and 10 ml dimethyl sulfoxide (DMSO) was stirred under at 7O-75°C for 45 minutes. The resulting dark solution was cooled to 5°C. To this was added a solution of 5.88 g (12 mmoles) of (4-carboxybutyl)triphenylphosphonium iodide in 10 ml DMSO. The resulting dark-red solution was stirred for 30 minutes at ambient temperature and cooled to 5°C. To this solution was added 1.36 g (4 mmoles) of the lactol produced in the previous step dissolved in 2 ml DMSO. The resulting mixture was allowed to stir for 15 hr. at room t£tU* S ύ The mixture was added to ice and water (200 ml) and the solution extracted with petroleum ether (40-60°C) and diethyl ether to remove neutral impurities. The aqueous phase was acidified with oxalic acid to pH 2 and extracted with diethyl ether (3 x 50 ml). The organic layer was washed with a saturated sodium chloride solution dried over sodium sulphate and filtered. Evaporation of the solvent in vacuo gave crude product as an oil which was immediately hydrolysed by stirring a solution of it in 10 ml acetic acid/water (7:3) for 4 hr. at ambient tempora25 ture. Evaporation of the solvent under reduced pressure below 50°C yielded an oil (1.82 g). This was chromatographed on preparative tic plates with glacial acetic acid/ethyl acetate (2:98) to give 500 mg of compound (v) as an oil and 300 mg of the slightly more polar compound (va) as an oil which crystallized upon standing. Compound (va) was recrystallized from diethyl ether-petroleum ether (bp 40-60°C) at 4°C. - 34 42941 OH (v) RS-C-15-QH (va) S-C-15-OH Compound (va) Found C 67,0; H 9,4 ’ C19H32°5 c 67’° H 9,7 mp 66-67°C (¾26 + 59° (c l,3-CHCl3) v max CHCl- 3450 (OH) 1720 (C=0) and 1610 (CH=CH) -1 J cm N.M.R. in CDCl., .0 50,89 (3H, t, J = 6,0 Hz, CH^-CH^) 51,20-2,26 (15H, ra, H-8 and CH2 of aliphatic chains) 62,33 (2H, t, J = 7,0 Hz -CH2-CO2H) 53,77-4,22 (4H, m, H-9, H-10 (α+β) and H-15) .5 54,31 (IH, t, H-12, Jg g = J12 3 = 4,0 Hz) 54,3 (2Ξ, m, H-5 and H-6) 65,68 (2H, ra, H-13 and H-14) 65,20 (3H, (broad) OH and C02H disappears upon addition of D20) :0 Enantiomeric mixture (v) Analysis Found ; C 66,9 H 9,5 C19H32°5 re<Iu;i-res c 67H 9,7 {a}D26 + 42 (c 1,4 CHC13) vmax CHCl3 3400 (OH), 1720 (C=0) and 1610 (CH=CH) cm“l 4294 - 35 N.M.R. in CDCl. 50,89 (3H, t, .T = 6,0 Hz, -CHg-CHg) 51,20-2,26 (15H, H-8 and CHg of aliphatic chains) 52,34 (2H, t, J = 7,0 Hz, -CHg-COgH) 53,60-4,40 (5H, m, H-9, H-10 (α+β), H-12 and H-l ) 55,20 (broad singlet 3H, OH and COgH disappears upon addition of DgO) §5,46 (2H, 31, H-5 and H-6) 55,69 (2H, m, K-I3 and H-14).

Claims (11)

1. A compound of the formula wherein B may. be in the a- or β-configuration and is a 5 group of formula : r 2 och 2 - or r 3 och 2 chV in which R 2 , R 3 and R^ are the same or different and each represents an alkyl, substituted alkyl or acyl group or, when B is in the β-configuration and X is a hydrogen atom, LO a hydrogen atom, or R 3 and R^ together form a carbonyl group? and X is a- or β-ΟΗ, or a hydrogen atom when B is in the β-configuration.

2. A compound according to claim 1, in which the L5 alkyl or substituted alkyl group is trityl, benzyl or methyl.

3. A compound according to claim 1, in which the acyl group is benzoyl or acetyl.

4. A compound selected from* 20 5,6-di-0-acyl-3-C-(carboxymethyl-2,3-γ-lactone)-3-deoxyD-gulofuranose? 5. ,6-di-0-acyl-3-C-(carboxymethyl-2,3-γ-lactone)-3-deoxyD-allofuranose; - 37 Λ, ί- : . / ί, Α, * 5-O-acyl-3-C-(carboxymethyl-2,3-γ-lactone)-3-deoxy-Dribofuranose; 5-O-acyl-3-C-(carboxymethyl-2,3-γ-lactone)-3-deoxy-Llyxofuranose; 5 3-C-(carboxymethyl-2,3-γ-1&οθοηβ)-3~deoxy-0-gulofuranose 5.5- carbonate; 3-C-(carboxymethyl-2,3-y-lactone)-3-deoxy-D-allofuranose 5.5- carbonate; 3-C-(carboxymethyl-2,3-y-lactone)-3-deoxy-5-0-methyl10 rioofuranose; 3-C-(carboxymethyl-2,3-γ-lactone)-3-deoxy-5-0-methyi-Llyxofurano se; 1,4-anhydro-3-C-(carboxymethyl-2,3-γ-lactone)-3-deoxy-Daliitol and 15 1,4-anhydro-3-C-(carboxymethyl-2,3-γ-lactone)-3-deoxy-Bribitol.

5. A method of preparing a compound of claim 1 wherein X is a- or β-ΟΗ, which comprises hydrolysing with an aqueous acid a compound of the formula XIV wherein B is a group of the formula BLOCH-- or R-OCH-CH2 2 3 2| v in which Rg, Rg and R^ are the same or different and each represents an alkyl, substituted alkyl, or acyl group, or R- and R^ together form a carbonyl group, V is a group of the formula S/' 5 /χ in which R and R. are the same or different and each is 5 6 hydrogen or an alkyl group or Rg and Rg together complete a carbocyclic ring containing 4- to 6 carbon atoms, and Z is a hydrocarbyl group.

6. A method according to claim 5, in which the compound of formula XIV is prepared by (a) reacting a compound of formula III 3 0 OH III OH in which B is as defined in Claim 1, with a compound of formula x C=0 in which R_ and R. are as defined in claim 5, so as to 5 6 form an acetal compound of formula IV B .0. IV (b) oxidizing the compound of formula IV so as to form a compound of formula V - 39 10 (c) condensing the compound of formula V with a phosphonate ylid so as to form a compound of formula VI B 0 X— -0 U > o x CH I cooz in which Z is a hydrocarbyl group; and (d) selectively reducing the compound of formula VI.

7. A method according to claim 5, in which the compound of formula XIV, in which B is in the oconfiguration, is prepared by (a) reacting a compound of formula III 1 B 0 \ x Χ^,ΟΗ /Γ III' OH in which B is as defined in claim 1, with a compound Of formula R„ C=0 in which Rg and Rg are as defined in claim 5, so as to form an acetal compound of formula IV' ’X 5 'όΕ IV (b) oxidising the compound of formula IV so as to form a compound of formula V (c) condensing the compound of formula V 1 with a phosphonate ylid so as to form a compound of formula Via: ---0 \ y Via in which Z is a hydrocarbyl group; (d) isomerising the compound of formula Via into a 0 compound of formula VII VII and (e) selectively reducing the compound of formula VII & c. /3 ·' •ϋ ¢4( C <£ _ - 41

8. A compound as claimed in claim 1 substantially as herein described.

9. A method of preparing a compound of claim 1 substantially as herein described with reference to the 5 accompanying drawing.

10. A method of preparing a compound of claim I substantially as herein described with reference to the Examples.

11. A compound of claim 1 when prepared by a method 10 of any one of claims 5, 6, 7, 9 and 10.