Synthesis of 2,4-dideoxy-4-hydroxyphosphonoyl-D-erythro- and -L-threo-pentofuranoses

摘要

J. CHEM. SOC. PERKIN TRANS. I 1992 Synthesis of 2,4-Dideoxy-4-hydroxyphosphonoyl-~-erythro-and -L-fhreo-pentofuranoses Tadashi Hanaya,a Ayashi Noguchi,a Margaret-Ann Armour,b Alan M. Hoggb and Hiroshi Yamamoto *A a Department of Chemistry, Faculty of Science, Okayama University, Tsushima, Oka yama 700, Japan Department of Chemistry, The University of Alberta, Edmonton, Alberta, T6G 2G2, Canada Treatment of 3,5, 6-trideoxy-I ,2-0-isopropylidene-6-nitro-~-~-erythro-hex-5-enofuranosewith di- methyl phosphonate in the presence of triethylamine, followed by catalytic hydrogenation and then deamination with nitrous acid, provided mainly a 2 :1 mixture of 3,5-dideoxy-5-dimethoxy-p hos phinoyI-1 ,2 -0-is0 prop y 1 id e n e-a-D-rib0 -a n d -p-L-/yxo-hexof ura nose in 57 ove raII yieId.T h is mixture was deacetonated, oxidized with sodium periodate, and then treated with acidic methanol to afford methyl 2,4-d ideoxy- 4-d imet hoxyp hosp h inoyl-a,p-D-erythro-pentopyra nosides (41 over-all yield from the aforementioned phosphinoylfuranose) and -L-threo-pentopyranosides (I7 overall yield). The major products were reduced with sodium dihydrobis- (2-methoxyethoxy) -aluminate, followed by hydrolysis with acid and then oxidation with hydrogen peroxide, to afford the title D-erythro compounds, whereas similar treatment of the minor pyranosides afforded the corresponding L-threo-pentofuranoses. These compounds were converted into the corresponding 1,3,5-tri-O-acetyl-5-methoxyphosphonoyl derivatives, whose structures and conformations mostly 3T2(~) for the other were established by spectroscopy. for one and 2T3(~) In view of the wide interest in their chemical and biochemical trideoxy-1,2-O-isopropylidene-6-nitro-a-~-~r~f~ro-hex-5-eno-properties, various sugar analogues having a phosphorus atom furanose 5 l1 proceeded smoothly at 25 Tin the presence of in the hemiacetal ring have been prepared in recent years: e.g., triethylamine (TEA) to give a 66:34 mixture of the a-D-ribo- analogues of D-glucopyranose 12-4 and D-ribofuranose 2.5-7 and P-L-lyxo-hexofuranose 6 in 94 yield (Scheme 1); these At the same time, other heteroatom-in-the-ring sugar analogues two compounds remained inseparable even upon repeated of the 2-deoxypentose type have drawn considerable interest chromatography.The exact assignment of the configuration of from the viewpoint of their potential derivatization to the major and minor products, respectively, to D-ribo and ~-lyxo nucleosides and nucleotides. For example, the preparation of was possible only after these compounds had been converted methyl 2-deoxy-4-thio-~-erythro-pentofuranoside3* and the into their methyl pentopyranosides 16 and 17 (see later). isolation of 1,2,4-trideoxy-l74-imino-~-ery?hro-pentitol4have Hydrogenation of compound 6 in methanol in the presence of been reported. We now describe our detailed study on the platinum(1v) oxide afforded compound 7 which, on deamin- synthesis of hydroxyphosphonoyl-in-the-ringsugar analogues ation with nitrous acid, provided a 2:l mixture of the 33- having a 2-deoxy-~-ribofuranose structure.dideoxy-D-rzbo- and -L-ljrxo-hexofuranose 8 (in 6 17; yield from An addition reaction of dimethyl phosphonate to 3,5,6-6), along with minor amounts of the dehydrated product 9 (1273, 6-chloro compounds 10 (873, and 6-O-acetyl com- hPOHU HOPOMe Hop pounds 11 (7) (Scheme 1). Compound 9 was derived from HO the chloride 10 by treatment with 1,8-diazabicyclo5.4.Oundec-7-ene (DBU), whereas compound 11 was converted into the HO corresponding alcohol 8 by treatment with sodium methoxide. OH HO OH HO HO Attempted deacetonation of compound 8 by acid hydrolysis and then acetylation (for the purposes of confirmation of 1 (R=OH, Et) 2 (R=OH, Et, Ph) 3 4 products) resulted in the formation of a considerable amount 0 CH~NH~OHCI Me0.U I 5 6 7 11 10 9 8 Scheme 1 Rqgenr.v: i, HP(=O)(OMe),.TEA; ii, H,, PtO,, HCl; iii, NaNO,, AcOH 6Ac 6' OAc 12 13 Scheme 2 Rcwgcnrs: i, H +;ii, Ac,O, py of a 1,6-anhydro-~-~-riho-hexofuranosederivative 13 (25) besides the desired triacetates 12 (60) (Scheme 2). The structure of the bicycle 13 was established by 'H NMR and mass spectrometry. The axial 6-H proton (6-Hax), which is trans-diaxial to the 5-phosphinoyl group (J6ax,P33.4 Hz), shows an NOE enhancement with the 2-H and 3-H, protons (see Experimental section). The presence of long-range coupling between P-5 and 3-H, (J3s,p4.3 Hzj supports the ~-riho configuration of compound 13. Alternatively, compounds 8 were first treated with acetic anhydride-sulfuric acid at 25 "Cfor 4 h (to yield triacetates 12) and then with sodium methoxide in methanol, thus giving the D-er)V/?ro-hexofuranoses 14 in 91 yield (Scheme 3).Periodate oxidation of trio114gave the (4RS)-3-0-forrnyl-~-gl~~ero-pento-pyranoses 15 which, upon treatment with methanol in the presence of an acidic ion-exchange resin followed by chroma- tographic separation, provided methyl 2,4-dideoxy-4-dimeth- oxyphosphinoyl-~-~-er~~t/~ro-pentopyranos~de(16a, 16 over- all yield from 14), its p-anomer 16b (29), the corresponding x-L-threo-pentopyranoside 17a (1573, and its p-anomer 17b (3.8). Besides these four epimers, minor amounts of the following 3-0-methyl derivatives were also obtained unexpec- tedly: 18a (2.2 from 14), 18b (4.8"/,), 19a (6.3"/,), and 19b (1.7).Although these 3-0-methyl products appear to be formed as the result of an acid-catalysed p-elimination of formate from compound 15 and subsequent addition of MeOH to the A3.4-pentose inermediate, the exact mechanism remains to be further studied. The structural and conformational assignments of these eight compounds (1619a, b) were made on the basis of their NMR 0 CH20H MeO, IIi. ii8 -OH 14 0 II (Me0)2pvMe +OR O'R R=H 17b R = Me 19b 1 7a 1 9a OMe16a, b 2 OH 20 H2ppoMe17a, b HO II,OH lrOMevi, vii -"OPOH Aviii ix AcOPOAc OH AcO 21 22 0 0 FrOMePo"-P O H -vi, viii :,OH viii, ix AcO OH OAc HO J. CHEM. soc. PERKIN TRANS. I 1992 data (see Experimental section).The presence of C-2-phosphorus coupling (3J2.p1G13 Hz) in the 13CNMR spectra and of equatorial 2-H (2-He,)-phosphorus coupling (J,,,., 4-6 Hz) in the 'H NMR spectra indicates that all of these compounds have conformations in which the dimethoxyphos- phinoyl group is equatorial. The smaller magnitude of the J3,4-values (2-3 Hz) in compounds 16 and 18 implies the D-cvythro configuration with 4C,(~)conformation. In contrast, the larger magnitude of J3.4(9-1 1 Hz) for compounds 17 and 19 supports the L-tlireo configuration with 'C,(L) conformation. The anomeric orientation at C-1 is readily perceived by the magnitude of J,.zax;namely, 3.44.3 Hz for 1619a (x-anomers) and 7.9-8.5 Hz for 1619b (P-anomers). The major, ~,P-D-cYJ~~/woproducts 16a, b were then reduced with sodium dihydrobis-(2-methoxyethoxy)aluminate(SDMA) to give the 4-phosphino derivative 20 which, by the action of hydrochloric acid in aq.propan-2-01 and then oxidation with hydrogen peroxide, afforded 2,4-dideoxy-4-hydroxyphos-phonoyl-~-er~~r/tro-pentofuranoses21 (Scheme 3). As the separation and purification of compound 21 was extremely difficult, unambiguous structural assignment was made by its conversion into the 4-methoxyphosphonoyl tri- acetates 22 by treatment with acetic anhydride-pyridine and then ethereal diazomethane. After purification of the crude products by column chromatography on silica gel, the follow- ing four diastereoisomers were obtained, although some of the minor products were not completely separable (see Experimental section): 1,3,5-tri-0-acetyl-2,4-dideoxy-4-C(R)-methoxyphos-phonoy~-~-~-er~~t/?ro-pentofuranose22a (6.1"/, overall yield from 16), its x-anomer 22b (3.9:4), the corresponding 4-(S)- methoxyphosphonoyl-p-isomer 22c (7.5'4, and its x-isomer 22d (5.2).Similar treatment of the minor, x,P-~-t/treoproducts 17a, b afforded 2,4-dideoxy-4-hydroxyphosphonoyl-~-t/ir~~~-pentofur- anoses 24 vicr 5-phosphino compounds 23 (Scheme 3). Compound 24 was also converted into 4-methoxyphosphonoyl triacetates 25: 1,3,5-tri-O-acetyl-2,4-dideoxy-4-(R)-methoxyphosphonoyl-x-~-t/~reo-pentofurano~e25a ( 1 1"/, from 17), its p-anomer 25b (5.40/,), the corresponding 4-(S)- iii MeO' OCHO OR bR bMe 16b 16a 18b 18a 0 0 23 24 25 Scheme 3 Rcrtgcwls: i, Ac,O, H,SO,: ii, NaOMe; iii, NaIO,; iv.MeOH. Amberlite (H'); v, SDMA; vi. H +; vii, HzOz:viii. AczO, Py: ix. CH,N, J. CHEM. SOC. PERKIN TRANS. I 1992 0 0 OMe OMe ACOCH~ c! ..OMe AcOCH2 ..OMe AcOCH2 1.-OMe AcOCH2 6:::Z-OvoAL0 A*oAC A S O A ~AWoAc ASOA~ amp;-::;-' AcOCH2 Aamp; H* 22a 0 0 OAc OAC 25a 25b methoxyphosphonoyl-Z-isomer 25c (4.8), and its p-anomer 25d (2.4'4). The molecular composition of compounds 22a-d and 25a-d was confirmed by their EI, high-resolution mass spectra, most of which gave the (M + 1) ions at m/z 322 corresponding to C,,H,,O,P. As the C-4 configuration of compounds 22a-d (D-erj+rkro) and 25a-d (L-threo) is maintained during the transformation from substrates 16a, b and 17a, b, the favoured conformations of the furanoid ring, the anomeric orientation of C-1, and the orientation of the ring P=O group of these triacetates are established by analysis of their 500 MHz 'H NMR spectra; see Table 1 for the assignments of all signals.Compounds 22W have large J,,,-values (27-29 Hz) and small J,.,-values (5-6 Hz) and thus are considered to exist predominantly in the T2 conformation. The relatively large J2,,3-and J,.,-values (8-10 Hz) of these compounds further support the above conformation. In contrast, compounds 25a-d have small J,.,-values (2-8 Hz) and large values for J3,p(25-32 Hz) and J,.., (2632 Hz), therefore existing predominantly in the * T3conformation; the relatively small J,..,-values (2-4 Hz) support this conformation.Compound 22a has appreciably close J2,p (1 1 Hz)-values compared with those (19 Hz) and J3,p of its stereoisomers 22b-d. This suggests an averaging between the interconverting 'T2 and 2T3conformations with a slight tendency towards ,T2 form (cu. 3:2), judging from the magnitudes of the corresponding J-values. The presence of a small, long-range, W-coupling (J1 ,, 0.5 Hz) observed for species 22a, c and 25b, d indicates, respectively, the p-D-and P-L-configuration for I-H of these compounds. The orientation of the ring P=O group was established by examination of the amp;values of 3-H for compounds 22a-d and of 2-H for 25a-d. Namely, a slight downfield shift of the 3-H signals was observed for compounds 22a and 22b compared with those of the respective anomers 22c and 22d, thus showing nearly a 1,3-diaxial proximity of the P=O group to 3-H in the case of isomers 22a and 22b {i.e., both possess a 4-(I?,) configuration).A similar downfield shift indicative of the same configuration of the ring phosphorus was observed for the 2-H signals of isomers 25a and 25b (in comparison with those of the corresponding diastereoisomers 25c and 25d). The rest of the spectral data of compounds 22a-d and 25a-d are completely in conformity with the structures shown. It has often been rather difficult2-3.5 to determine the exact configurations of methoxyphosphonoyl sugar analogues com- pared with the case of the corresponding alkyl- or aryl-phosphonoyl congeners..4-6.7 Therefore, a complete set of the present data summarized in Table 1 is of high value in the structural analysis of related 2,4-dideoxy-4-phosphonoyl-pentofuranoses, some of which are currently being prepared. Experimental M.p.s were determined with a Yanagimoto MP-S3 instrument and are uncorrected. All reactions were monitored by TLC 22b 22c 22d -6Ac OAc 25c 25d (Merck silica gel 60F, 0.25 mm) with an appropriate solvent system AcOEt (Solvent A); (19: 1) Ac0Et:EtOH (Solvent B); (19:1) CHC1,-MeOH (Solvent C); and (5:3:1) propan-2-01- AcOEt-water (Solvent D); components were detected by spraying of the plates with 20 sulfuric acid-thanol, with subsequent heating. Column chromatography was performed by Wako C-200 silica gel.The NMR spectra were measured in CDCI, with Varian VXR-500 (500 MHz for 'H, 126 MHz for I3C) and VXR-200 (81 MHz for ,'P) instruments (the SC-NMR Lab., Okayama Univ.) at 21 "C, unless otherwise stated. Chemical shifts are reported as amp;values relative to tetramethylsilane (internal standard for 'H and I3C) and 85 phosphoric acid (external standard for ,'P). J Values are given in Hz. The assignments of all signals were made by employing a first-order analysis with the aid of decoupling techniques and, if necessary, 2D COSY and NOEDS measurements. The mass spectra were taken on an A.E.I. MS 50 ultra-high-resolution instrument and were given in terms of m/z (relative intensity) compared with the base peak.3,5,6- Tr ideosy- 5-dimethoxyphosphinoyf-1,2-0-isoprupyf-idene-6-nitro-x-~-ribo-and -~-L-lyxo-hexofuranose 6.-TEA (0.60 cm3, 4.3 mmol) was added dropwise at 0 "C to a mixture of compound 5 l1 (3.00 g, 13.9 mmol) and dimethyl phos- phonate (1 5.0 g, 136 mmol), and the mixture was stirred for 1 h at 25 "C. The excess of phosphonate was distilled off at -40 "C (0.2 Torr). The residue was purified on a column of silica gel with AcOEt-hexane as eluent, giving an inseparable mixture of the he-xojurunoses 6 (ribo:Iyxo 66: 34) as a syrup (4.22 g, 9473, the ratio being determined by 'H and ,'P NMR spectroscopy Found: C, 40.4; H, 6.1; N, 4.0; (M' -CH,), 310.0690. CloH2,N08P requires C, 40.62; H, 6.20 N, 4.3104; (M -15), 310.06921; R, 0.37 (Solvent A); 6, for ribo-6 1.30 and 1.50 (3 H, each, 2 x s, CMe,), 1.73 (1 H, ddd, J3R.3S 13.7, J3R.4 10.7, J2.3R 4.9, 3-H,), 2.37 (1 H, dd, J3s.4 4.4, J2,3s -0, 3-H,), 3.04 (1 H,ddt, J5,p21.1, J4.58.2, 6.2, J5.6 6.0,5-H), 3.77 and 3.78 3 H each, 2 x d, JPOMe10.7 and 10.9, P(OMe),, 4.40 (1 H, dddd, J4.p 6.6,4-H), 4.64 (1 H, td, J6.6, 14.6, Jb,.p 14.3,6-H'), 4.73 (1 H, ddd, J6,p16.0, 6-H), 4.74 (1 H, dd, J1., 3.8, 2-H) and 5.76 (1 H, d, 1-H); 6, for ribo-6 26.01 and 26.61 (CMe,), 38.49 (3J,,p3.5, C-3), 39.84 (1J5.p 141.2, C-5), 53.05 and 53.38 (2Jc.p 6.9 and 6.3, MeOP), 71.89 (C-6), 74.16 (C-4), 80.41 (C-2), 104.87 (C-1) and 11 1.53 (Me,C); 6, for riho-6 25.0; 6, for lj,.ro-6 1.30 and 1.49 (3 H each, 2 x s, CMe,), 2.07 (1 H, ddd, J3R.3S 13.5, J3~.4 10.9, J2.3R 4.8, 3-H,), 2.17 (1 H, dd, J3s.4 4.6, J2.3s -0, 3-H,), 3.33 (1 H, dddd, J5.p 23.1, J5.6' 7.3, J5.6 5.9, J4.5 3.5, 5-H), 3.76 and 3.78 3 H each, 2 d, JpOMe 10.8, P(OMe),, 4.52 (1 H, dddd, J4.p 16.3, 4-H), 4.60 (1 H, ddd, J6.6.14.1, J6e.p 10.6, 6-H'), 4.61 (1 H, ddd, J6.p 10.8, 6-H), 4.75 (1 H, dd, J1.2 3.6, 2-H) and 5.78 (1 H, d, 1-H); 6, for 1v.w-6 26.05 and 26.68 (Me,C), 35.49 (C-3), 38.05 (1J5.p 140.7, C-5), 52.73 and 53.33 (,Jeep 6.4 and 6.3, MeOP), 71.70 (C-6), 74.81 (C-4), 80.33 (C-2), 105.20 (C-1) and 111.72 (Me2C); 6, for fj*so-6 24.4; nz/z 310 298 J. CHEM. SOC. PERKIN TRANS. I 1992 Table I 'H and 31PNMR parameters for compounds 22ad and 25a4 in CDCl, Chemical shifts (6) Compound 1-H 2-H 2-H' 3-H 4-H 5-H 5-H' POMe 1-, 3-.and 5-OAc" 31P 22a 5.07 2.45 2.13' 5.28 2.39 4.39 4.28 3.87 2.16,2.07, 2.07 56.5 22b 5.03 2.73 1.95 5.13 2.44 4.35 4.35 3.83 2.13, 2.07, 2.06 55.2 22c 5.12 2.42 2.18 5.20 2.50 4.31 4.22 3.79 2.12, 2.08, 2.07 54.0 22d 4.82 2.69 2.05' 4.98 2.59 4.33 4.24 3.88 2.17, 2.08, 2.07 52.2 25a 4.66 2.14b 2.60 5.52 2.59 4.34 4.2 1 3.91 2.18, 2.07,2.04 54.3 25b 4.93 2.24 2.49 5.38 2.55 4.36 4.26 3.79 2.10, 2.07, 2.06 60.5 2 5.15 I .96 2.62 5.48 2.52 4.37 4.32 3.83 2.12,2.11, 2.05 54.9 25d 4.96 2.14b 2.51 5.3 1 2.4 1 4.43 4.38 3.88 2.14,2.11, 2.05 60.5 Coupling constants (Hz) 22a 5.0 7.2 0.5 4.9 5.3 19.0 14.3 7.1 c 7.4 10.6 7.0 7.8 16.3 9.9 13.8 11.7 11.2 22b 5.1 7.2 0 7.0 6.9 28.7 14.2 7.9 7.0 8.0 5.9 7.3 7.3 17.0 12.7 12.7 10.9 22c 3.3 4.9 0.5 5.8 5.6 27.1 14.4 9.6 7.4 8.4 5.3 7.4 7.9 16.4 16.4 8.8 11.3 10.8 22d 5.0 8.8 0 8.8 6.5 28.1 14.0 8.5 c 9.3 5.3 7.2 7.6 15.8 15.8 8.8 11.4 10.9 25a 10.9 8.6 0 4.9 3.4 c 14.4 2.6 31.7 5.0 30.7 9.5 6.0 18.4 9.2 4.9 11.3 11.2 25b 6.9 1.6 0.5 2.8 3.4 2.4 16.1 2.3 26.6 5.0 32.2 8.6 6.6 17.5 11.1 5.2 11.2 11.0 2 8.8 7.8 0 5.8 4.3 8.3 14.4 4.2 25.7 5.0 25.4 7.8 8.3 15.9 8.7 13.1 11.3 10.8 25d 7.8 2.1 0.5 2.7 3.6 c 15.5 3.4 26.2 5.1 29.5 6.6 8.2 16.4 7.8 8.6 11.4 10.8 "Acetoxy assignments may have to be interchanged.bChemical shifts were confirmed by 2D COSY experiments in spite of the presence of overlapping acetoxy signals. 'Values are uncertain because of overlap with acetoxy signals.(M+ -CH3,61), 268 (loo), 250 (19), 221 (IS), 210 (to), 203 J4,58.0, J5,6r4.8, J5,64.1, 5-H), 3.75 and 3.79 3 H each, 2 x d, (2 191 (6.6), 165 (15), 149 (47), 137 (57) and 109 (45). JpOMe 10.9 and 10.7, P(OMe),, 3.87 (1 H, td, J6,,, 11.5,J6r.p10.5, 6-H'), 3.95 (1 H, ddd, J6.p 24.9, 6-H), 4.57 (1 H, dtd, J4,p 8.9, 4- 1,2-0-isoprop~didene-a-H), 4.74 (1 H, dd, J,,,3.6,2-H) and 5.78 (1 H, d, 1-H);6, for ribo-33-Dideoxy-5-dimethoxyphosphinoyl-D-ribo-and -P-L-lyxo-hexofuranose 8, 6-Chloro-6-deoxy Deriv- 10 26.6; BP for Iyxo-10 25.7; m/z 301 (M+ -CH3, lo), 299 atives 10, 6-O-Acetyl Derivatives 11, and 3,5,6-Trideoxy-5- (M+ -CH,, 28), 257 (55)and 239 (14). dimethoxyphosphinoyl-1,2-0-isopropylidene-x-~-erythro-hex-5-Fraction B Rf0.31 (Solvent B) gave 6-O-acety1compounds enofuranose 9.-Compounds 6 (3.78 g, 11.6 mmol) dissolved in 11 (ribo:lyxo 2:l) as a syrup (275 mg, 7) Found: (M + l)+, a mixture of methanol (100 cm3) and 2 mol dm-, hydrochloric 339.1224.C13H2408P requires (M + l), 339.12091; 6, for acid (5.80 cm3, 11.6 mmol) were hydrogenolysed in the presence ribo-11 1.31 and 1.50 (3 H each, 2 x s, CMe,), 1.87 (1 H, ddd, 13.5, J3~,411.0, J2.3, 4.8, ~-HR), of platinum(1v) oxide (670 mg, 2.95 mol) at 25 "C under an J~R,~s 2.05 (3 H, S, 6-OAc), atmospheric pressure of H,. After 16 h, the catalyst was filtered 2.24 (1 H, dd, J3s.4 4.2, J2,3s -0, 3-H,), 2.38 (1 H, ddt, J5,p off, and the filtrate was evaporated under reduced pressure to 21.7, J4.5 7.1, J5.6, 5.2, J5.6 4.9, 5-H), 3.75 and 3.77 3 H each, give the 6-aminohexofuranose hydrochloride derivative 7 as a 2 x d, JpOMe 10.9, P(OMe),, 4.39 (1 H, ddd, J6,,, 13.9, J6,6.syrup; R, 0.39 (Solvent D). 11.5, 6-H'), 4.43 (1 H, ddd, J6,p 19.6, 6-H), 4.47 (1 H, tdd, J4,p To a stirred solution of the amine 7 in water (35 cm3) at 0 "C 10.0, 4-H), 4.73 (1 H, dd, J1,,3.6, 2-H) and 5.78 (1 H, d, 1-H); were added acetic acid (3.0 cm3, 52.4 mmol) and then sodium 6, for ribo-11 27.3; 6, for ly-xo-11 1.31 and 1.50 (3 H each, nitrite (4.60 g, 66.7 mmol). After 2 h, the mixture was extracted 2 x s, CMe,), 2.13-2.15 (2 H, m, 3-HR,s), 2.55 (1 H, ddd, J5.p twice with CHCI,. The combined organic layers were washed 22.2, J,.,. 7.6, J5.65.0, J4,53.9, 5-H), 3.74 and 3.76 3 H each, successively with aq. NaHCO, and water, dried (Na,SO,), and 2 X d, JpOMe 10.8, P(OMe),, 4.28 (1 H, td, J6.6r= J6,,, = 11.3, evaporated under reduced pressure.The residue was separated 6-H'), 4.40 (1 H, m, 6-H), 4.53 (1 H, dddd, J4,, 18.4, J3R,49.0, by column chromatography, giving three fractions, A-C. J3s.4 7.0, 4-H), 4.73 (1 H, dd, J2,3R 4.8, J1.2 3.7, J2,3,y -0, 2-H) Fraction A R,0.42 (Solvent B) gave a syrup (680 mg) and 5.82 (1 H, d, 1-H); 6, for 1y.xo-11 26.7; m/z 339 (M' + 1, which consisted of the hexenofuranose 9 (12 from 6) 18), 323 (loo), 281 (90), 263 (ll), 239 (53), 221 (54), 203 (31), Found: (M+ -CH,), 263.0686. CloH1606P requires 191 (14), 179 (12), 137 (64), and 109 (31). (M -15), 263.06853 and the chloride 10 (8, ribo:lyxo -3:1) Fraction C R,0.20 (Solvent B) gave a 2:l mixture of the Found: (M' -CH,), 301.0423 and 299.0447.CloH,,C106P he.wfuranoses 8 as a syrup (2.11 g, 61) Found: C, 45.0 H, requires (M -15), 301.0422 and 299.04511, the relative 7.4; (M + l)+, 297.1108. CllH2107P requires C, 44.60; H, amounts of products 9 and 10 being determined by the intensity 7.14;(M + l), 297.1 1031; 6, for ribo-8 1.31 and 1.51 (3 H each, ratio of their l-H signals; 6, for 9 1.32 and 1.52 (3 H each, 2 x s, CMe,), 1.73 (1 H, ddd, J3R,3S13.7,J3R,410.8,J2,3R 4.8, 3-2 x s, CMe,), 1.74 (1 H, ddd, J3R,3S13.5, J,,., 10.9, J2.3~4.7, HR), 2.20 (1 H, ddt, J5.p 20.3,J4.5 9.0, J5.6 5.7,J5.6~5.5,5-H), 2.30 ~-HR), -0,3-HS),3.76and2.39 (1 H, dd, J3S.4 4.5, J,,,, -0, 3-H,), 3.73 6 H, d, (lH,brs,OH),2.34(1H,dd,J3S,44.3,J2,3S JpOMe 10.9, P(OMe),, 4.76 (1 H, dd, J1,, 3.6, 2-H), 4.79 (1 H, 3.78 3 H each, 2 x d, JpOMe 10.8 and 10.9,P(OMe),, 3.98 (1 H, = J4.3~)1.5, 4-H), 5.88 (1 H, d, I-H), 6.12 ddd, J6e.p 17.2,J6.6, 11.7, 6-H'), 4.00 (I H, ddd, J6.p 15.8, 6-H),tdt, J4.p 9.2, J4,6(~) 1.6, 6-H(Z) and 6.19 I H, dt, 4.40 (1 H, dddd, J4., 6.1, 4-H), 4.73 (1 H, dd, Jl.23.6, 2-H) andI H, dt, J6(~).p22.6, J~(z).~(E) 1.31 and 1.51 (3 J6(E).P45.9, 6-H(E); 6, for 9 18.0 m/z 263 (M+ -CH,, 5.79(1 H, d, 1-H);6, for ribo-8 28.7; 6, for 1~9.~0-8 480/,), 221 (loo), 203 (32), 191 (7), 175 (15), 163 (47), 137 (29) H, each, 2 x s, CMe,), 1.92 (1 H, ddd, J,,.,, 13.6, J3R.411.1, 2.20 (1 H, dd, J3S.4 4.8, J2.3, -0, 3-H,), 2.30 and 109 (22); 6, for ribo-10 1.29 and 1.51 (3 H each, 2 x s, J2.3, 4.7, ~-HR), 21.4, J4,55.7, J5.65.6,J5.6,5.0,CMe,), 1.89 (1 H, ddd, J,,,,, 13.6,J3R,411.0, J2.3~4.7, 3-HR), (lH, br s, OH) 2.46 (1 H, dq, JSqp 2.26 (1 H, dd, J3s.44.3, J,,,, -0, 3-Hs), 2.42 (1 H, ddt, J5.,22.0, 5-H), 3.77 and 3.79 3 H, each, 2 x d, JpOMe 11.1 and 11.0, J.CHEM. SOC. PERKIN TRANS. 1 1992 P(OMe),, 3.90 (1 H, ddd, J6j.p 18.2,J6,6, 11.7, 6-H'), 3.92 (1 H, ddd, J6,p 15.3, 6-H), 4.55 (1 H, tt, J4,p 10.1, 4-H), 4.75 (1 H, dd, J1,,3.7, 2-H) and 5.82 (1 H, d, 1-H); dP for lyxo-8 29.0; m/z 297 (M' + 1,2.6), 281 (85),239 (loo),221 (25), 209 (17), 191 (23), 179 (17), 153 (32), 137 (29) and 109 (27). Dehydrochlorination of Compound 10.-To a solution of compound 10 (350 mg, 1.1 1 mmol) and the hexenofuranose 9 (460 mg) in dry CH,Cl, (10 cm3) at 0 "C was added DBU (0.20 cm3, 1.3 mmol).The mixture was stirred for 2 h at 25 "C, and then concentrated under reduced pressure. The residue was purified by column chromatography to give the hexeno- furanose 9 (745 mg, 92) as a syrup. Deacetylation of6-Acetate 11.-To a solution of the acetate 11 (120 mg, 0.355 mmol) in abs. methanol (1.0 cm3) at 0 "C was added a 25 methanolic solution of NaOMe (0.010 cm3, 0.044 mmol), and the mixture was stirred for 30 min before being neutralized with Amberlite IR-120 (H'). The resin was filtered off and washed with MeOH. The combined filtrate and washings were evaporated under reduced pressure. The residue was purified by column chromatography to give compounds 8 (ribo: lyxo 2: 1) (96.0 mg, 91).Acid Hjidrolysis and Acetylation of Compounds -Corn-pounds 8 (55 mg, 0.19 mmol) were dissolved in a mixture of propan-2-01 (0.2 cm3) and 0.25 mol dm-, hydrochloric acid (1.8 cm3), and the mixture was then refluxed for 2 h. The reactants were neutralized with Amberlite IRA-45. The resin was filtered off and the filtrate was evaporated under reduced pressure. The residue was acetylated with acetic anhydride (0.5 cm3) and dry pyridine (1.0 cm'), worked up, and separated by column chromatography into two fractions. The faster eluting fraction R,0.34 (Solvent B) gave (5RS)-1,2,6-tri-O-acetyl-3,5-dideoxy-5-dimethoxyphosphinoyl-a,~-~-into To a cold solution of the above compound 12 in abs. MeOH (10 cm3) was added a 25 methanolic solution of NaOMe (0.40 cm3, 1.7 mmol), and the mixture was stirred at 0 "C for 1 h before being neutralized with Amberlite IR-120 (H+) ion-exchange resin.The resin was filtered off and washed with MeOH. The filtrate was evaporated under reduced pressure to give the hexofuranose 14 (675 mg, 91) as a syrup; R,0.55 (Solvent D); 6,(60 MHz) 2.00-2.35 (3 H, m, 3-H, and 5-H), 3.25-3.60 (3 H, m, 1-, 2-, and 6-OH, D,O-exchangeable), 3.78 6 H, d, JPOMe11.0, P(OMe),, 3.90-4.85 (4 H, m, 2-, 4-H, and 6-H2) and 5.28 (1 H, br s, 1-H). Methyl 2,4-Dideoxy-4-dimethoxyphosphinoyl-a-~-erythro-pentopyranoside 16a, the P-Anomer 16b, the x-L-threo-Pento-pyranoside 17a, the 0-Anomer 17b, Methyl 2,4-Dideoxy-4- dimethoxyphosphinoyl-3-O-methyl-a-~-erythro-pentopyrano-side 18a, the P-Anomer 18b, the a-L-threo-Pentopyranoside 19a and the P-homer 19b.-Sodium periodate (750 mg, 3.51 mmol) was added to a solution of trio1 14 (675 mg, 2.63 mmol) in water (5.0 cm3) at 0 "C.The solution was then stirred at 25 "C for 4 h and triturated with ethanol (50 cm3). The precipitate was filtered off, and the filtrate was evaporated ~~ under reduced pressure. The residue was extracted with CHCl,, dried (Na,SO,), and evaporated under reduced pressure tb give (4RS)-2,4-dideoxy-4-dimethoxyphosphinoyl-3-O-formyl-a,P-D-glycero-pentopyranoses 15 as a syrup: R,0.63 (Solvent D); 6,(60 MHz) 1.80-2.50 (3 H, m, 2-H, and 4-H), 3.32 (1 H, br s, OH, D,O-exchangeable), 3.74 and 3.76 3 H each, 2 x d, JpOMe 10.8, P(OMe),, 3.7M.30 (3 H, m, 1-H and 5-H,), 4.75-5.25 (1 H, m, 3-H), and 8.08 (1 H, br s, 3-OCHO).A solution of formate 15and Amberlite IR-120 (H') (7 cm3) in abs. methanol (15 cm3) was refluxed for 8 h. The mixture was evaporated under reduced pressure to give a pale yellow syrup, which was separated by column chromatography with a gradient eluent of CHCl, -(19:l) CHC1,-MeOH erythro-hexofuranoses 12 as a syrup (44 mg, 60); 6, for the predominant component (presumably 1,2,6-tri-O-acetyl-3,5-dideoxy-5-dimethoxyphosphinoyl-~-~-ribo-hexofuranose)2.05, 2.07 and 2.08 (3 H each, 3 x s, AcO), 2.26 (1 H, dd, J,,,,, 14.5, J3s.4 6.1, 3-Hs), 2.32 (1 H, ddd, J3~,49.7, J2,3R 4.4, ~-HR), 2.33 (1 H,ddt, J5+p21.8,J4.59.7,J5,6 = J5,6, = 4.8, 5-H), 3.77 6 H, d, JPOMe10.9, P(OMe),, 4.35-4.42 (2 H, m, 6-H,), 4.70 (1 H, tt, J4,p6.4, 4-H), 5.15 (1 H, dd, JIs20.8, 2-H) and 6.12 (1 H, d, 1-H).The slower eluting fraction R,0.25 (Solvent B) gave 2-0-acetyl-1,6-anhydro-3,5-dideoxy-5-dimethoxyphosphinoyl-p-D-rho-hexofuranose 13 as a syrup (13 mg, 25) Found: C, 43.2; H, 6.45; M', 280.0723. CloH1707Prequires C, 42.86; H, 6.11; M, 280.07121; 6, 1.77 (1 H, br dd, J5,p19.9, J5,6ax5.0, Js,~~,1.0, J4.5 0.5, 5-H), 2.07 (3 H, S, AcO), 2.15 (1 H, dddd, J,,,,, 14.2, J3s,46.9, J3s,p4.3, J2,3s3.0, 3-H,), 2.35 (1 H, br dd, J2-3, 7.3, J3~,40.5, ~-HR),3.78 and 3.88 3 H each, 2 d, JpOMe 10.8, P(OMe),, 4.02 (1 H, ddd, J6ax,p 33.4, J6ax,6eq12.8, 6-Ha,), 4.14 (1 H, br t, J6eq,P13.4, 6-He,), 5.08 (1 H, br t, J4,p7.3,4-H), 5.30 (1 H, br s, Jl,,0.5, 1-H) and 5.37 (1 H, br dd, 2-H); NOEDS experiment observed NOES() by irradiation of 6-Ha,: 5-H 14, 3-H, 5.2, 2-H 11; 6p 28.2; m/z 280 (M', 4.4), 238 (99), 221 (4.6), 209 (72), 192 (15), 179 (32), 163 (36), 137 (86), and 110 (loo).(5RS)-3,5-Dideoxy-5-dimethoxyphosphinoyl-a,~-~-erythro-hexofirranose 14.-Conc. sulfuric acid (0.20 cm3) was added to a solution of compound 8 (860 mg, 2.90 mmol) in acetic anhydride (10 cm3)at 0 "C.The mixture was stirred at 25 "C for 4 h, diluted with CHCI,, and washed successively with cold aq. NaHCO, and water. The organic layer was dried (Na,S04), and evaporated under reduced pressure to give 1,2,6-tri-O-acetyl derivative 12 (1.08 g) as a syrup.four fractions, A-D. Fraction A R,0.40 (Solvent C) gave a mixture (1 10 mg) of the 3-O-methyl-~-erythro-pentopyranosidesMa, b and the 3-O-methyl-~-threo-pentopyranosides19a, b as a syrup (see later). Fraction B R,0.34 (Solvent C) gave the x-D-erythro- pentopyranoside 16a as needles (98.2 mg, 16 from 14), m.p. 106-107deg;C (from AcOEt-hexane) Found: C, 40.1; H, 7.3; (M + l)', 241.0832. C8H1706P requires C, 40.00; H, 7.13; (M + l), 241.08411; 6" 1.82 (1 H, dt, J2ax,2eq =14.5, J1+2ax J2ax.3 = 3v5, 2-Hax), l.99 (1 H, dddd, JZeq,P 6e4, J2eq.3 3.09J1,Zeq 1.4, 2-He,), 2.32 (1 H, dddd, J4,p 21.7, J4,5ax12.0,J4.5eq4.6, J3.4 2.3,4-H), 3.37 (3 H, s, 1-OMe), 3.70 (1 H, br s, HO), 3.73 (1 H, m, 5-He,), 3.74, 3.75 3 H each, 2 x d, JpOMe 10.8 and 11.0, P(OMe),, 4.10 (1 H, td, J5ax,P11.7, 5-Ha,), 4.31 (1 H, dq, J3,p 6.6, J1,,2.0, 3-H) and 4.76 (1 H, dt, 1-H); 6, 35.48 (3J,,, 11.4, C-2), 40.18 (1J4.p142.0, C-4), 52.46 (2Jc,p7.0, MeOP), 52.84 (2Jc,p6.5, MeOP), 53.77 (,J5,, 3.9, C-5), 55.50 (1-OMe), 62.95 (2J3,p6.7, C-3) and 98.19 (C-1); 6, 28.0; m/z 241 (M' + 1, 0.273, 225 (0.4), 208 (24), 191 (40), 180 (ll), 154 (38), 149 (30), 137 (loo), and 109 (32) Fraction C R,0.29 (Solvent C) gave a syrup (121 mg) which consisted of the L-threo-pentopyranosides 17a (1 5 from 14) and 17b (3.8), the relative amounts being determined from the integral ratio of their 1-H and 1-OMe signals Found: (M + l)', 241.0848.CgH,806P requires (M + l), 241.08411; 6, for 17a 1.58 (1 H, ddd, J2ax,2eq13.3, J2ax.3 10.9, J1.Zax 3.6, 2-Hax), 2.13 (1 H, dddd, J4,p 16.1, J3.4 10.7, J4.5ax 9.5, J4.5eq 7-59 4-H), 2.14 (1 H, dtd, J2eq.p 5-97JZeq.3 4-99 J1,Zeq 1-59 2-Heq), 3.31 (3 H, s, 1-OMe), 3.70-3.73 (2 H, m, 5-H,), 3.77 and 3.79 3 H each, 2 x d, JpOMe 10.9, P(OMe),, 3.93 (1 H, br s, HO), 4.21 (1 H, tdd, J3,p8.2, 3-H) and 4.80 (1 H, dt, J1,5eq2.2, 1-H); 6, for 17a 37.84 (,J,,, 13.3, C-2), 42.57 (1J4.p136.3, C-4h 52.67 ('JcsP8.2, MeOP), 52.80 (2Jc,p7.7, MeOP), 54.89 (1-OMe), 56.58 (2J5.p-0, C-5), 62.49 ('J3,, 6.3, C-3) and 99.98 (C-1); S, for 17a 28.8; 6, for 17b 1.55 (1 H, ddd, J2eq,2ax13.1, JZax.3 9.2, J1.2ax 7.9, 2-Ha,), 2.13 (1 H, dtd, J4.p 16.5, J3,4 9.5, J4.5ax 8.9, J4,5eq 4-39 4-H), 2-28 (1 H, dtd, J2eq.3 4.5, J2eq.P 4-37 J1,2eq2.4, 2-He,), 3.07 (1 H, br s, HO), 3.45 (3 H, s, 1-OMe), 3.52 (1 H, ddd, JSeq,sax12.3, JSax,,4.4, 5-Ha,), 3.77 and 3.79 3 H, each, 2 x d, JpOMe 11.0, 10.8, P(OMe),, 4.05 (1 H, tdd, J3.p7.0, 3-H), 4.12 (1 H, ddd, JSeq.,10.6, 5-He,) and 4.40 (1 H, dd, 1-H); 6, for 17b 28.9; m/= 241 (M+ + I, O.lx), 208 (13), 191 (26), 180 (13), 154 (54), 137 (100) and 109 (29).Fraction D R,0.24 (Solvent C) gave the P-D-erythro- pentopyranoside 16b as needles (184 mg, 29 from 14), m.p. 101-102 "C (from AcOEt-hexane) Found: C, 40.2; H, 7.3; (M + l)', 241.0837. C8H,,06P requires C, 40.00; H, 7.13; (M + 1), 241.0841); BH 1.61 (1 H, ddd, JZax.Zeq 13.5, JI,tax 8.2, J2ax.3 2.8, Z-HaX), 2.04 (1 H, dtd, J2eq.3 = J2eq.P = 4.8, J1,Zeq 2.5, 2-He,), 2.31 (1 H, dddd, J4,p 21.0, J4,Sax 10.0, J4,Seq 4.4, J3.4 2.8, 4-H), 3.44 (1 H, s, 1-OMe), 3.75 (1 H, br s, HO), 3.76 6 H, d, JmMe 10.9, P(OMe),l, 3-96 (1 H, dddd, JSax,Seq 11.7, JSeq,P 7.9, J3.Seq 0.8, 5-He,), 4.02 (1 euro;4, ddd, JSax,p 3.5, Skia,), 4.43 ' (1 H, ddtd, J3,p11.6, 3-H) and 4.74 (1 H, dd, 1-H); 6, 37.74 (3J2.p10.4, C-2), 39.67 ('J4,, 137.2, C-4), 52.71 (2Jc,p7.0, MeOP), 52.89 f2JC,,6.2, MeOP), 56.22 (1-OMe), 59.47 (2Js.p 3.1, C-5), 64.15 (2J3s,5.4, C-3) and 99.10 (C-1); 6, 29.3; m/z 241 (M+ + 1, 0.5), 208 (17), 191 (17), 154 (30), 149 (41), 137 (100) and 109 (30).Fraction A (110mg) was rechromatographed with a gradient eluent of AcOEt -(19: 1) AcOEt-EtOH into three fractions, A 1-A3. Fraction A, Rf0.42 (Solvent B) gave the a-L-threo-pento- pyranoside 19a as a syrup (41.9 mg, 6.3 from 14) Found: C, 42.3; H, 7.75; (M + l)+, 255.0983.C9HI9O6P requires C, 42.52; H, 7.53; (M + l), 255.09981; 6, 1.47 (1 H, ddd, 12ax.2eq 12-7,J2ax.3 10.8, J1,Zax 3m4, 2-Hax), 2-18 H, dtd, J4.P 16.6, J4.Sax 11.0, J3,4 10.1, J4.5eq 5.9,4-H), 2.26 (1 H. ddd, JZeq,p 5.8, JZeq.3 2.0, 2-He,), 3.31 (3 H, s, 1-OMe), 3.38 (3 H, 4.5, J1,2eq s, 3-OMe), 3.73 and 3.75 3 H each, 2 x d, JpOMe 11.0 and 10.8, P(OMe),, 3.8C3.84 (2 H, m, 5-H,), 3.87 (1 H, tdd, J3,, 8.1, 3-H) and 4.80 (1 H, dt, J1,Seq2.3, 1-H); Bc 34.97 (3J2,,11.5, C-2), 41.31 ('J4,, 139.4, C-4), 51.92 ('JC., 6.9, MeOP), 52.83 ('JC,,6.2, MeOP), 54.78 and 55.99 (1- and 3-OMe), 57.90 (2Js,p -0, C-5), 72.20 ('J,., 6.4, C-3) and 98.80 (C-1); 6, 28.5; FAB m/z 255 (M+ + 1, 25), 237 (223), 191 (loo), 185 (19) and 93 (32). Fraction A2 Rf 0.36 (Solvent B) gave a syrup (43.6 mg) which consisted of the p-anomers 18b (4.8 from 14) and 19b (1.773, the relative amounts being determined from the integral ratio of their 1-H and I-, 3-OMe signals; hHfor 18b 1.53 (1 H, ddd, J~ax,Zeq 13.7, J1,2ax 7-97 JZax.3 3.2, 2-H,,), 2-24 (1 H, dtd, J2cq.3 = JZeq.p = 4.9, J1.teq 2.7, 2-He,), 2-35 (1 H, dddd, J4,p J. CHEM.SOC. PERKIN TRANS. I 1992 each, 2 x d, JPOMe10.9 and 10.8, P(OMe),, 3.84 (1 H, dqd, J3.p 9.1, J1,31.0, 3-H), 4.16 (1 H, td, JSax.P2.4, 5-Ha,) and 4.62 (1 H, ddd, 1-H); 6, 28.4. 1,3,5-Tri-O-ucetj+2,4-dideo-~y-4-( and S)-metho.yjyphos-R phono)~l-x,P-~-erythro-pentofurunose22a-d.-To a stirred solution of compounds 16a, b (200 mg, 0.822 mmol) in dry benzene (3 cm3) at 5 "C was added a solution of SDMA (3.4 mol dm-3 in toluene; 0.90 cm3, 3.1 mmol) in dry benzene (1 cm3) in small portions under argon.The mixture was stirred at this temperature for 30 min. Water (0.5 cm3) was added and the mixture was stirred for a further 30 min. The precipitate was centrifuged and, after removal of the supernatant, extracted with several portions of benzene. The organic layers were combined, and evaporated under reduced pressure to give the 4-phosphino derivative 20 as a syrup: R, 0.50 (Solvent C). The above syrup was immediately treated at 90deg;C with propan-2-01 (1.5 cm3) and 0.5 mol dm-3 hydrochloric acid (3 cm3) for 1 h under argon.After cooling, the reactants were neutralized with Amberlite IRA-45. The resin was filtered off and washed with water, and the filtrate was evaporated under reduced pressure. The residue was dissolved in water (1.5 cm3), treated, at 25 "C, with 30 aq. hydrogen peroxide (0.3 cm3) for 10 h, and concentrated under reduced pressure to give crude 2,4-dideoxy-4-hydroxyphosphonoyl-x,P-~-erythro-pen-tofuranoses 21 as a syrup: R,0.15-0.10 (Solvent D). This product was acetylated with acetic anhydride (0.5 cm3) in dry pyridine (1.5 cm3) for 1 d at 25 "C and the mixture was then concentrated under reduced pressure. The residue was passed through a column of Amberlite IR-120 (15 cm3) and the eluent was concentrated under reduced pressure.The residue was dissolved in dry CH2C12 (1 cm3) and methylated with ethereal diazomethane, at 0 "C. The solvent was evaporated off under reduced pressure and the residue was separated by column chromatography with a gradient eluent of (3 : 1) AcOEt-hexane -+ AcOEt, into two fractions, A and B. Fraction A Rf 0.45 (Solvent A) gave a syrup (26.4 mg) which consisted of the 4-(R)-metho.~yphosphonoy/-P-~-erythro-pentofuranose 22a (6.1 from 16) and the correspond- ing x-isomer 22b (3.979, the relative amounts being determined from the integral ratio of their 1-H and MeOP signals Found: (M+ -CH2CO), 280.0713. Cl0HI7O7Prequires (M -42), 280.07121; 'H and 31P NMR data, see Table 1; ni/z 280 (M+ -CH2C0, 2.9), 238 (loo), 178 (10) and 150 (22).Fraction B R,0.42 (Solvent A) gave a syrup (33.6 mg) which consisted of the 4-(S)-metho.~yphosp/zonoy/-~-isumer 22c (7.5 from 16) and its corresponding x-isomer 22d (5.2) Found: C, 45.1; H, 6.2; (M + I)+, 323.0893. C1,H,,O,P requires C, 44.73; H, 5.94; (M + l), 323.08961; 'H and 31P NMR data, see Table 1; mj: 323 (M + + 1, 2.5), 280 (17), 238 (loo), 220 (22), 209 (30), 178 (39), 150 (56) and 123 (25). 20.6, J4.5ar 10.0,J4,5eq4.2,J3.43.0,4-H),3.43and3.44(3H,each, 2 x s, 1-and 3-OMe), 3.72 and 3.75 3 H each, 2 x d, JpOMe 10.9, P(OMe),, 3.90-3.99 (3 H, m, 3-H and 5-H,) and 4.64 (1 H, dd, 1-H); 6, for 18b 28.5; 6H for 19b 1.39 (1 H, ddd, JZax,Zeq 12.9, JZax.3 10.1, J1.2ax 8.5, 2-Ha,), 2.13 (1 H, dtd, J4.p 18.0, J4,5ax 10.3, J3.4 9.5, J4.Seq 4.5, 4-H), 2.37 (1 H, dtd, JZeq,3 = JZeq.p = 4.8, Jl.2eq 2.6, 2-He,), 3.46 and 3.47 (3 H each, 2 x s, 1-and 3-OMe), 3.52 (1 H, ddd, JSax.Seq 12.3, JSax.p 3.8, 5-Ha,), 3.68 (1 H, tdd, J3.p 8.5, 3-H), 3.73 and 3.75 3 H each, 2 x d, JpOMe 11.0 and 10.8, P(OMe),, 4.17 (1 H, ddd, JSeq.,7.6, 5-He,) and 4.30 (1 H, dd, 1-H); 6, for 19b 28.7.Fraction A3 R, 0.27 (Solvent B) gave the pyranoside 18a as a syrup (14.8 mg, 2.2 from 14); 6, 1.68 (1 H, dt, J2ax.2eq 14.8, J1.Zax 4.37Jzax.3 3-79 2-HaXA 2-18(1 H, dddd, J2eq,p 5.8, JZeq,33.6, J1.2eq 2-07 '-Heq), 2.39 (1 H, ddt, J4.p 21.3, J4.Sax 10.7, J4.5eq 4.2, -73.4 3-1,4-Hk 3.36 (3 H, S, 1-OMe), 3.42 (3 H, s, 3-OMe), 3.58 (' ddd, J~eq.~ax11-37J5eq.P 5.9, 5-He,), 3.71 and 3.75 3 H '7 1,3,5-Tri-O-acetj*l-2,4-dideo~~j~-4-( S)-metho.xjphos-R and phonojfJ-+L-threo-pentojuranoses 25a-d.-The procedures similar to those for the preparation of compounds 22 from substrates 16 were employed.Thus, compounds 17a, b (1 11 mg, 0.456 mmol) were converted into the diiasfereoisonzeric pentofurunoses 25 via intermediates 23 and 24. The crude product 25 was separated by column chromatography into three fractions, A-C. Fraction A R,0.39 (Solvent A) gave the 4-(R)-metho.uy-phosphonoyl-x-L-threo-pentofuranose25a (1 6.6 mg, t tyofrom 17) as a syrup Found: C, 45.0; H, 6.15; (M+ -CH,CO), 280.0711. CI2Hl90,P requires C, 44.73; H, 5.947:); (M -42), 280.07121; 'H and 3'P NMR data, see Table 1; mji 280 (M +. -CH2CO,6.3"/;;), 238 ( loo),220 ( 18, 178 ( 15)and 150(25).Fraction euro;3 R, 0.36 (Solvent A) gave a syrup (10.5 mg) which consisted of the 4-(S)-methoxyphosphonoyl-~-isomer J.CHEM. SOC. PERKIN TRANS. I 1992 25c (4.8from 17) and its p-isomer 25d (2.4); 'H and 31P NMR data, see Table 1. Fraction C Rf0.31 (Solvent A) gave the 4-(R)-metho.uy-phosphono~~l-p-isomer25b (8.0 mg, 5.4from 17) as a syrup Found: (M + l)+, 323.0890. C,,H,,O,P requires (M + l), 323.08961; 'H and 31PNMR data, see Table 1; m/z 323 (M+ + 1, 0.2), 280 (5.3), 238 (loo), 220 (8.5), 209 (lo), 178 ( 16) and 150 (24). References For reviews, see H. Yamamoto and T. Hanaya, Sfudies in Natural Producrs Chernisrrjq, ed. T. 1. Atta-ur-Rahman, Elsevier, Amsterdam, 1990, vol.6, pp. 351 384; H. Yamamoto and S. Inokawa, Adn Curbohydr. Chem. Biochem., 1984,42, 1 35. T. Richter, P. Luger, T. Hanaya and H. Yamamoto, Curbohydr.Rex, 1989, 193, 9. H. Yamamoto, T. Hanaya, H. Kawamoto, S. Inokawa, M. Yamashita, M.-A. Armour and T. T. Nakashima, J. Org. Chem., 1985,50,3516. 301 4 H. Yamamoto, K. Yamamoto, S. Inokawa, M. Yamashita, M.-A. Armour and T. T. Nakashima, J. Org. Chem., 1983,48,435. 5 T. Hanaya and H. Yamamoto, Bull. Chem. SOL'.Jpn., 1989,62.2320. 6 P. Luger, E. Muller, H. Yamamoto and S. Inokawa, Curbohydr.Res., 1985, 145, 25. 7 H. Yamamoto, Y. Nakamura, S. Inokawa, M. Yamashita, M.-A. Armour and T. T. Nakashima, J. Org. Chem., 1984,49, 1364. 8 U. G. Nayak and R. L.Whistler, JUSIUSLiehigs Ann. Chem., 1970, 741, 131; Y.-L. Fu and M. Bobek, J. Org. Chem., 197641, 3831. 9 R. J. Nash, E. A. Bell, G. W. J. Fleet, R. H. Jones and J. M. Williams, J. Chem. Soc., Chem. Commun., 1985, 738. 10 Some of the results have been reported as a preliminary communication: T. Hanaya, A. Noguchi and H. Yamamoto, Curbohydr. Rex, 1991,209, C9. 11 J. M. J. Tronchet, K. D. Pallie and F. Barbalet-Rey, J. Curbohj-dr. Chem., 1985,4, 29. Paper 1 /033 15H Received 2nd July 1991 Accepted 17th September 1991 (c-Copyright 1992 by the Royal Society of Chemistry Ninth International Conference on Organic Synthesis ICOS 92 Montreal, Canada CIS0 92 Hosted by Universite du Quebec a Montreal June 28-July 2, 1992 Main Theme: Stereocontrol in Organic Synthesis TOPICS WILL INCLUDE: Strategies and Reagents for Stereocontrol in Synthesis Advances in Asymmetric Synthesis Biomolecules in Organic Synthesis LECTURERS: The following have agreed to present plenary lectures: P. Deslongchamps (CANADA) D. Evans (U.S.A.)L. Ghosez (BELGIUM) T. Hayashi (JAPAN) I.-F. Normant (FRANCE) G. Pattenden (U.K.) P.G. Schultz (U.S.A.) D. Seebach (SWITZERLAND) K.B. Sharpless (U.S.A.) G. Stork (U.S.A.) LOCAL ORGANIZING Chairman: Robert N. Young COMMITTEE: Co-chairmen: Sandu Goldstein Andree tefebvre Yvon Pepin Jean-Cloude Richer FOR MORE INFORMATION AND Professeur Jean-Claude Richer TO RECEIVE A SECOND Departement de chimie _-CIRCULAR PLEASE CONTACT: Universite de Montreal ._..'7 C.P. 61 28, succursale A Montreal (Quebec) IUPAC Canada H3C 3J7 lntern~tional Fax: 514 343-6624 Union of Pure and Applied Cbemistry