A stereoselective synthesis of the reported structure of polyporolide

Abstract

Polyporolide, isolated from a basidiomycete, was assigned a 4-hydroxy-5-(1-hydroxyhexyl)-dihydrofuran-2-one structure with anti-placement of the three contiguous stereocenters. A stereoselective total synthesis of the reported structure of the natural product involving two different routes is presented. A comparison of the spectral data of the synthesized molecule indicates the need for structure revision of natural polyporolide.

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Introduction

The secondary metabolites generated by Polyporus species (basidiomycetes) are structurally diverse and biologically active. In 2006, Wei and co-workers isolated a new acetogenin, polyporolide 1 (Fig. 1) from the mycelial solid cultures of Polyporus strain SC0652.¹ They observed this strain to possess antibacterial activity against E. coli. Polyporolide showed weak activity against brine shrimps (Artemia salina) with LC₅₀ of 424.5 μg mL⁻¹. The structure of 1 was established by extensive spectroscopic studies. The relative configuration in 1 was assigned based on the NMR data and NOESY studies. They observed that H-3 and H-4 were anti-configured. Similarly, H-4 and H-5 were erythro-configured as shown in Fig. 1.¹

Fig. 1 Polyporolide 1.

In the course of our synthetic studies directed toward the enantioselective synthesis of pharmacologically active natural products like paraconic acids and butyrolactones,² we became interested in synthesis of the newly isolated acetogenin, polyporolide 1.

Results and discussion

Our detailed retrosynthetic approach for polyporolide 1 is outlined in Scheme 1. We visualized the γ-butyrolactone moiety in 1 can be accessed from 2 by aldol-type acetate anion addition and cyclization. Compound 2 with anti-diol group can be accessed from epoxide 3. The latter can be derived from (E)-2-octen-1-ol 6 through Sharpless asymmetric epoxidation.³ Alternatively, (S)-1-octen-3-ol 5 can be derived from 2. From this, homoacrylate ester formation and ring closing metathesis would give 4. cis-Dihydroxylation⁴ of olefin 4 and trans-lactonization was expected to give 1.

Scheme 1 Retrosynthetic analysis for polyporolide 1.

The forward synthesis of polyporolide started from known (E)-2-octen-1-ol 6⁵ (Scheme 2). The Sharpless asymmetric epoxidation,³ of 6 in presence of (+)-DIPT, Ti(Oi-Pr)₄ and TBHP in CH₂Cl₂ at −30 °C furnished the epoxy alcohol 3 in 85% yield and excellent >98% ee.⁶ Regioselective opening of epoxide ring under Payne rearrangement⁷ conditions delivered the anti-triol 7 in 71% yield. Monoprotection of primary alcohol as silyl ether (8, 76%) and acetonide protection of the internal diol furnished 9 (82%). Removal of TBS protection with TBAF liberated the primary alcohol 2 in 86% yield. The two carbon homologation was planned through aldol-type acetate anion addition. We anticipated as reported in literature⁸ the acetate anion addition on such vicinal acetonide containing aldehydes to deliver anti-C3/C4 steroegenic centres. DMP (Dess–Martin periodinane) oxidation of primary alcohol 2 to aldehyde and subsequent addition of lithiated ethyl acetate gave diastereoselectively 10 as single diastereomer in 54% yield over two steps. Removal of acetonide protection and in situ lactonization produced polyporolide 1 in 77% yield, [α]²⁵_D = +4.5 (c = 0.1, MeOH). The IR spectral data of 1 was conclusive of γ-lactone structure (ν = 1770 cm⁻¹ for C=O). However, a comparison of ¹H-NMR and ¹³C-NMR data for synthesized 1 with that reported for the natural product¹ showed discrepancy.

Scheme 2 Synthesis of polyporolide 1: reagents and conditions: (a) Ti(O-iPr)₄, TBHP, (+)-DIPT, CH₂Cl₂, −30 °C, 12 h, 85%; (b) 0.5N NaOH, 1,4-dioxane, reflux, 48 h, 71%; (c) TBSOTf, Et₃N, THF, 0 °C to rt, 5 min, 76%; (d) (OMe)₂C(Me)₂, p-TsOH·2H₂O, CH₂Cl₂, rt, 4 h, 82%; (e) TBAF, THF, 0 °C to rt, 3 h, 86%; (f) (i) DMP, CH₂Cl₂, rt, 3 h (ii) DIPA, n-BuLi, THF, −78 °C, 30 min, then EtOAc, −78 °C, 25 min, then aldehyde from 2, −78 °C, 4 h, 54% (two steps); (g) 4N HCl, MeOH, reflux, 8 h, 77%.

We explored an alternative strategy for polyporolide 1 as shown in Scheme 3. The acetonide alcohol 2 (from Scheme 2) was converted into iodide and subsequent zinc-mediated elimination provided (S)-1-octen-3-ol 5 in 80% yield from 2. Esterification of 5 with 3-butenoic acid 11 under Steglich conditions⁹ provided the diene 12 in 70% yield. The ring-closing metathesis¹⁰ of diene 12 with Grubbs-II catalyst (1.0 mol%) gave δ-lactone 4 in excellent yields of 96%. The subsequent Sharpless asymmetric dihydroxylation⁴ with (DHQ)₂-PHAL ligand gave the diol and in situ trans-lactonization (from 6-membered to 5-membered lactone) furnished polyporolide 1, [α]²⁵_D = +4.7 (c = 0.1, MeOH). The spectral data of this was same as that prepared in Scheme 2.

Scheme 3 Alternative synthesis of polyporolide 1: reagents and conditions: (a) (i) PPh₃, imidazole, I₂, THF, rt, 3 h, 93%, (ii) Zn, AcOH, Et₂O, rt, 4 h, 86%; (b) DCC, DMAP, CH₂Cl₂, 11, 0 °C to rt, 6 h, 70%; (c) Grubbs-II cat. (1 mol%), CH₂Cl₂, reflux, 12 h, 96%; (d) K₃Fe(CN)₆, K₂CO₃, MeSO₂NH₂, (DHQ)₂PHAL, K₂OsO₄·2H₂O, t-BuOH/H₂O (1 : 1), 0 °C, 24 h, 71%.

The ¹H NMR data for C3, C4 and C5 protons (chemical shifts values, δ ppm) for polyporolide 1,¹ synthetic 1, and related compounds: (+)-mupirocin H 13,¹¹ (−)-muricatacin 14¹² and (+)-δ-muricatacin 15¹³ are shown in Fig. 2. Polyporolide 1 is assigned the anti-relative stereochemistry for C3, C4 and C5 contiguous protons (Fig. 1).¹ Similar relative stereochemistry exists in (+)-mupirocin H 13. However, the chemical shifts values of reported 1 for C3, C4 and C5 protons as shown, completely mis-match with that in 13. But there exists a good match of these protons shifts of 13 with that of synthetic 1. A similar correlation can be extended for synthetic 1 with that of (−)-muricatacin 14 for C4 and C5 protons with regards to δ values. It can be further extended even to (+)-δ-muricatacin 15 for the C5 and C6 protons which are similar to C4 and C5 in polyporolide 1. The ¹³C NMR data for reported 1 for C3 (70.1), C4 (91.6) and C5 (71.4) do not match with that of synthetic 1 for C3 (67.9), C4 (91.6) and C5 (71.4), respectively. Thus, the synthetic 1 has the structure as depicted in Fig. 2. It is apparent from this mis-match of data of synthesised 1, that the proposed structure of polyporolide needs revision.

Fig. 2 Chemical shifts values (δ ppm) for molecules related to polyporolide 1.

Conclusions

In conclusion, a stereoselective synthesis of the reported structure of polyporolide 1 has been achieved in 7–9 steps and 12.3–13.5% overall yields. The key steps involve Sharpless epoxidation and diastereoselective aldol-type acetate anion addition. Alternatively ring-closing-metathesis, asymmetric dihydroxylation and trans-lactonizaton also yielded polyporolide 1. The reported polyporolide 1 had specific rotation value of [α]²⁰_D = +13.1 (c = 0.2, MeOH),¹ while the synthesized compound showed [α]²⁵_D = +4.7 (c = 0.1, MeOH). A comparison of the spectral data of synthetic 1 with that of proposed structure and known similar molecules is conclusive of the need of structure revision for proposed polyporolide.

Experimental section

General information

Solvents were dried by standard procedures. Thin-layer chromatography was performed on EM 250 Kieselgel 60 F254 silica gel plates. The spots were visualized by staining with KMnO₄ or by using UV lamp. ¹H-NMR and ¹³C-NMR were recorded on Varian 400, Bruker Avance^III 400 and 500 spectrometers and the chemical shifts are based on TMS peak at δ = 0.00 pm for proton NMR and CDCl₃ peak at δ = 77.00 ppm (t) in carbon NMR. IR spectra were obtained on Perkin Elmer Spectrum One FT-IR spectrometer. Optical rotations were measured with Jasco P-2000 digital polarimeter using Sodium D line (589 nm). HRMS were recorded using Micromass: Q-Tof micro (YA-105) spectrometer. Compound 6 was prepared following literature procedure.⁵

(2S,3S)-2,3-Epoxyoctan-1-ol (3)⁶. To flame dried molecular sieves 4 Å (0.7 g) in CH₂Cl₂ (15 mL) were added (+)-diisopropyl L-tartrate (95 mg, 0.406 mmol, 0.2 equiv.) and Ti(OiPr)₄ (0.12 mL, 0.406 mmol, 0.2 equiv.). The suspension was cooled to −30 °C and allyl alcohol 6 (0.260 g, 2.03 mmol) was added. The reaction mixture was then stirred for an additional 30 min, and then t-BuOOH (3.8 M solution in decane, 1.1 mL, 4.1 mmol, 2 equiv.) was added. The reaction mixture was stirred to −30 °C for 12 h. After completion of reaction, the mixture was quenched with water (15 mL) and NaOH solution (30% aq.). It was then treated with saturated aq. NaCl (20 mL), and the resulting mixture was stirred vigorously for an additional 30 min at room temperature. The mixture was then vacuum filtered through a pad of celite, and the filter cake was washed with CH₂Cl₂ (50 mL). The organic phase was separated, and the aqueous phase was extracted with CH₂Cl₂ (3 × 20 mL). The combined organic layers were washed with water, brine, dried (Na₂SO₄) and concentrated. The residue was purified by silica gel column chromatography using petroleum ether/EtOAc (4 : 1) as eluent to afford 3 (0.248 g, 85%) as colorless oil. [α]²⁵_D = −41.2 (c = 0.7, CHCl₃), lit.⁶ [α]²⁴_D = −43.0 (c = 0.45, CHCl₃). IR (CHCl₃): ν_max = 3424, 2952, 2929, 2859, 1457, 1158, 1109, 1045, 865, 704, 668 cm⁻¹. ¹H NMR (400 MHz, CDCl₃/TMS): δ 3.91 (dd, J = 12.6, 2.4 Hz, 1H), 3.62 (dd, J = 12.5, 4.3 Hz, 1H), 2.97–2.90 (m, 2H), 1.71 (br. s, 1H, OH), 1.59–1.53 (m, 2H), 1.48–1.39 (m, 2H), 1.36–1.27 (m, 4H), 0.89 (t, J = 7.1 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 61.7, 58.5, 56.02, 31.5, 31.46, 25.6, 22.5, 13.9 ppm.

(2R,3S)-Octane-1,2,3-triol (7). To a solution of epoxy alcohol 3 (0.5 g, 3.47 mmol) in 1,4-dioxane (10 mL) was added 0.5 N NaOH (2 mL) at room temperature. The mixture was stirred under reflux for 48 h, then cooled to room temperature and concentrated to a volume of 1.0 mL. The mixture was extracted with CH₂Cl₂ (3 × 10 mL). The combined organic layers were washed with water, brine, dried (Na₂SO₄) and concentrated. The reduced was purified by silica gel column chromatography using petroleum ether/EtOAc (1 : 1) to give compound 7 (0.399 g, 71%) as white solid. Mp 95–96 °C, [α]²⁵_D = −20.9 (c = 0.75, EtOH), lit.¹⁴ 104–105 °C, [α]²⁰_D = −21.4 (c = 0.98, EtOH). IR (CHCl₃): ν_max = 3398, 3018, 2956, 2932, 2873, 2861, 1466, 1072, 916, 880, 671 cm⁻¹. ¹H NMR (400 MHz, acetone-d6): δ 3.76–3.71 (m, 2H), 3.67–3.48 (m, 2H), 3.41 (dd, J = 10.4, 6.1 Hz, 1H), 1.68–1.52 (m, 2H), 1.43–1.27 (m, 6H), 0.88 (t, J = 6.8 Hz, 3H) ppm. ¹³C NMR (125 MHz, acetone-d6): δ 74.1, 71.9, 63.1, 32.4, 31.3, 24.7, 21.9, 13.0 ppm. HRMS: m/z calcd for C₈H₁₈O₃Na [M + Na]⁺ 185.1154; found: 185.1151.

(2R,3S)-1-(tert-Butyldimethylsilyloxy)octane-2,3-diol (8). To a stirred solution of 7 (150 mg, 0.925 mmol) in dry THF (6 mL) at 0 °C were sequentially added Et₃N (0.52 mL, 3.7 mmol, 4.0 equiv.) and TBSOTf (0.330 mL, 1.437 mmol, 1.55 equiv.). The reaction mixture was stirred at room temperature for 5 min. It was then quenched with water (0.2 mL) and the aqueous layer extracted with EtOAc (3 × 15 mL). The combined organic layers were washed with water, brine, dried (Na₂SO₄) and concentrated. The residue was purified by silica gel column chromatography using petroleum ether/EtOAc (17 : 3) as eluent to afford 8 (194.4 mg, 76%) as colorless oil. [α]²⁵_D = −5.2 (c = 0.4, CHCl₃). IR (CHCl₃): ν_max = 3305, 2949, 2929, 2857, 1464, 1252, 1095, 1068, 912, 836, 666 cm⁻¹. ¹H NMR (400 MHz, CDCl₃/TMS): δ 3.80–3.75 (m, 2H), 3.74–3.66 (m, 1H), 3.58–3.52 (m, 1H), 1.9 (br. s, 2H, OH), 1.52–1.25 (m, 8H), 0.92–0.84 (m, 12H), 0.07 (s, 6H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 73.5, 73.4, 64.1, 33.2, 32.1, 26.1, 25.9, 22.8, 18.4, 14.2, −5.2, −5.3 ppm. HRMS: m/z calcd for C₁₄H₃₂O₃SiNa [M + Na]⁺ 299.2013; found 299.2015.

(2R,3S)-1-(tert-Butyldimethylsilyloxy)-2,3-(isopropylidenedioxy) octane (9). To a solution of diol 8 (180 mg, 0.651 mmol) in CH₂Cl₂ (15 mL) was added pTsOH·2H₂O (4 mg) and 2,2-dimethoxypropane (0.28 mL, 2.28 mmol, 3.5 equiv.). The reaction mixture was stirred at room temperature for 4 h and then quenched with saturated aq. NaHCO₃ (0.5 mL) and stirred for additional 15 min. The solution was extracted with CH₂Cl₂ (3 × 15 mL) and the combined organic layers were washed with brine, dried (Na₂SO₄) and concentrated. The residue was purified by silica gel column chromatography using petroleum ether/EtOAc (9 : 1) as eluent to afford 9 (169 mg, 82%) as colorless oil. [α]²⁵_D = −3.2 (c = 0.3, CHCl₃). IR (CHCl₃): ν_max = 2957, 2931, 2859, 1464, 1380, 1364, 1260, 1097, 1046, 912, 839, 809, 777, 735, 672 cm⁻¹. ¹H NMR (400 MHz, CDCl₃/TMS): δ 4.15–4.10 (m, 1H), 4.08–4.03 (m, 1H), 3.66 (dd, J = 10.2, 7.4 Hz, 1H), 3.57 (dd, J = 10.3, 5.0 Hz, 1H), 1.60–1.48 (m, 3H), 1.41 (s, 3H), 1.38–1.25 (m, 5H), 1.33 (s, 3H), 0.91–0.86 (m, 12H), 0.06 (s, 3H), 0.057 (s, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 107.5, 77.9, 77.7, 62.1, 31.9, 29.0, 28.3, 26.4, 25.9, 25.6, 22.6, 18.2, 14.0, −5.4, −5.5 ppm. HRMS: m/z calcd for C₁₇H₃₆O₃SiNa [M + Na]⁺ 339.2326; found 339.2327.

(2R,3S)-2,3-(Isopropylidenedioxy)octan-1-ol (2). To a solution 9 (100 mg, 0.315 mmol) in dry THF (10 mL) was added TBAF (0.48 mL, 0.48 mmol, 1.5 equiv., 1 M solution in THF) at 0 °C and the mixture warmed to room temperature over 3 h. It was then quenched with water and stirred for 15 min. THF was removed under reduced pressure and the aqueous layer extracted with EtOAc (3 × 5 mL). The combined organic layers were washed with water, brine, dried (Na₂SO₄) and concentrated. The residue was purified by silica gel column chromatography using petroleum ether/EtOAc (4 : 1) as eluent to give 2 (55 mg, 86%) as colorless oil. [α]²⁵_D = 6.2 (c = 0.2, CHCl₃). IR (CHCl₃): ν_max = 3419, 2985, 2955, 2932, 2873, 1460, 1380, 1369, 1247, 1168, 1102, 1045, 881, 666 cm⁻¹. ¹H NMR (500 MHz, CDCl₃/TMS): δ 4.16–4.11 (m, 2H), 3.62–3.57 (m, 2H), 2.09 (br. s, 1H, OH), 1.57–1.23 (m, 8H), 1.46 (s, 3H), 1.35 (s, 3H), 0.88 (t, J = 7.0 Hz, 3H) ppm. ¹³C NMR (125 MHz, CDCl₃): δ 108.0, 77.9, 77.01, 61.8, 31.8, 28.8, 28.2, 26.3, 25.5, 22.5, 14.0 ppm. HRMS: m/z calcd for C₁₁H₂₂O₃Na [M + Na]⁺ 225.1461; found 225.1452.

Ethyl(3R,4S,5S)-3-hydroxy-4,5-(isopropylidenedioxy)decanoate (10). To a solution of alcohol 2 (0.052 g, 0.256 mmol) in CH₂Cl₂ (10 mL) was added Dess–Martin periodinane (0.152 g, 0.358 mmol, 1.4 equiv.) in one portion and the reaction mixture stirred at room temperature for 3 h. The mixture was then filtered through a celite pad and the filtrate concentrated under reduced pressure. The residue was purified by silica gel column chromatography using petroleum ether/EtOAc (9 : 1) as eluent to afford the corresponding aldehyde (50 mg) as colorless oil. This was immediately used in the next reaction.

To a solution of iPr₂NH (0.08 mL, 0.563 mmol, 2.2 equiv.) in dry THF (10 mL) was added nBuLi (1.6 M in THF, 0.34 mL, 0.54 mmol, 2.1 equiv.) dropwise at −78 °C. The reaction mixture was stirred for 30 min at −78 °C. A solution of ethylacetate (0.05 mL, 0.512 mmol, 2 equiv.) in dry THF was added over 10 min, and the resulting soln. was stirred for another 15 min. Then, the solution of above aldehyde (50 mg) in THF was added slowly at −78 °C. The resulting mixture was stirred further for 4 h at the same temp., followed by quenching the reaction with saturated aq. NH₄Cl soln. The aqueous layer was extracted with EtOAc (3 × 10 mL) and the combined organic layers were washed with water, brine, dried (Na₂SO₄) and concentrated. The residue was purified by silica gel column chromatography using petroleum ether/EtOAc (4 : 1) as eluent to give 10 (40 mg, 54% from 2) as colorless oil. [α]²⁵_D = −25.9 (c = 0.1, CHCl₃). IR (CHCl₃): ν_max = 3437, 2956, 2931, 2873, 1725, 1463, 1379, 1248, 1165, 1097, 1042, 699 cm⁻¹. ¹H NMR (400 MHz, CDCl₃/TMS): δ 4.21–4.15 (m, 3H), 4.07–4.02 (m, 1H), 3.88 (dd, J = 8.8, 5.7 Hz, 1H), 2.80 (dd, J = 17.1, 2.5 Hz, 1H), 2.49 (dd, J = 17.1, 9.0 Hz, 1H), 1.75–1.42 (m, 8H), 1.39 (s, 3H), 1.32 (s, 3H), 1.28 (t, J = 7.1 Hz, 3H), 0.89 (t, J = 6.9 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 173.5, 107.8, 79.0, 78.1, 66.6, 60.8, 38.4, 31.9, 29.3, 28.2, 26.3, 25.6, 22.6, 14.2, 14.0 ppm. HRMS: m/z calcd. for C₁₅H₂₈O₅Na [M + Na]⁺ 311.1829; found 3111.1821.

(4R,5S)-4-Hydroxy-5-[(S)-1-hydroxyhexyl]dihydrofuran-2(3H)-one (1). The ester 10 (30 mg, 0.104 mmol) was dissolved in methanol (10 mL) and 4 N HCl (2 mL) was added and refluxed for 8 h. The mixture was then cooled to room temperature and quenched with NaHCO₃ and filtered. The filtrate was concentrated and the residue purified by flash column chromatography using petroleum ether/EtOAc (1 : 1) as eluent to afford 1 (16.2 mg, 77%) as colorless oil. [α]²⁵_D = +4.5 (c = 0.1, MeOH). IR (CHCl₃): ν_max = 3428, 2956, 2928, 2858, 1770, 1468, 1378, 1262, 1197, 1075, 1056, 1004, 910, 839, 649 cm⁻¹. ¹H NMR (500 MHz, CDCl₃/TMS): δ 4.64 (t, J = 3.4 Hz, 1H), 4.23 (t, J = 3.4 Hz, 1H), 3.84 (t, J = 4.2 Hz, 1H), 2.94 (dd, J = 18.2, 7.3 Hz, 1H), 2.55 (br. s, 2H, OH), 2.53 (dd, J = 18.2, 4.0 Hz, 1H), 1.62–1.51 (m, 3H), 1.32–1.25 (m, 5H), 0.90 (t, J = 6.5 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 176.1, 89.8, 71.5, 67.9, 38.5, 32.6, 31.6, 25.2, 22.5, 14.00 ppm. HRMS: m/z calcd for C₁₀H₁₉O₄ [M + H]⁺ 203.1278; found 203.1279.

(S)-Oct-1-en-3-ol (5). To a mixture of triphenylphosphine (1.162 g, 4.43 mmol, 1.5 equiv.), imidazole (0.502 g, 7.38 mmol, 2.5 equiv.) and 2 (0.6 g, 2.95 mmol) in THF (30 mL) was added iodine (1.124 g, 4.43 mmol, 1.5 equiv.) portion wise at 0 °C. The resulting solution was stirred for 3 h at room temperature. The reaction was quenched by adding saturated aq. Na₂S₂O₃ and extracted with EtOAc (3 × 30 mL). The combined organic layers were washed with water, brine, dried (Na₂SO₄) and concentrated. The residue was purified by silica gel column chromatography using petroleum ether/EtOAc (9 : 1) as eluent to afford the corresponding iodide (0.862 g, 93%) as colorless oil. This was used immediately in next reaction.

To a solution of iodide (0.84 g, 2.68 mmol) in Et₂O (10 mL) at room temperature was added Zn dust (1.49 g, 22.78 mmol, 8.5 equiv.) and acetic acid (2 mL). The mixture was stirred for 4 h and then quenched with 2 N HCl and stirred for 5 min. The suspension was extracted with Et₂O (3 × 30 mL) and the combined organic layers were washed with water, brine, dried (Na₂SO₄) and concentrated. The residue was purified by silica gel column chromatography using petroleum ether/CH₂Cl₂ (4 : 1) as eluent to afford 5 (0.295 g, 86%) as colorless oil. [α]²⁵_D = +9.2 (c = 0.16, CHCl₃), lit.¹⁵ [α]²⁵_D = +9.0 (c = 0.4, CHCl₃). IR (CHCl₃): ν_max = 3434, 2956, 2932, 2859, 1648, 1464, 1380, 1262, 1092, 1036, 925, 867 cm⁻¹. ¹H NMR (400 MHz, CDCl₃/TMS): δ = 5.87 (ddd, J = 17.2, 10.5, 6.4 Hz, 1H), 5.22 (td, J = 17.2, 1.4 Hz, 1H), 5.10 (td, J = 10.4, 1.3 Hz, 1H), 4.13–4.07 (m, 1H), 1.59–1.24 (m, 9H), 0.88 (t, J = 7.2 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 141.3, 114.6, 73.3, 37.0, 31.7, 25.0, 22.6, 14.0 ppm. HRMS: m/z calcd for C₈H₁₆OK [M + K]⁺ 167.0838; found 167.0839.

(S)-Oct-1-en-3-yl but-3-enoate (12). To a solution of the allylic alcohol 5 (0.34 g, 2.65 mmol) in CH₂Cl₂ (20 mL) were added 3-butenoic acid 11 (1.14 g, 13.25 mmol, 5.0 equiv.), DCC (1.094 g, 5.30 mmol, 2.0 equiv.) and DMAP (33 mg, 0.27 mmol, 10 mol%) at 0 °C. The mixture was warmed to room temperature and stirred for 6 h. It was then quenched with 2 N HCl. The suspension was extracted with CH₂Cl₂ (3 × 30 mL) and the combined organic layers were washed with water, brine, dried (Na₂SO₄) and concentrated. The residue was purified by silica gel column chromatography using the petroleum ether/CH₂Cl₂ as eluent to afford 12 (0.364 g, 70%) as colorless oil. [α]²⁵_D = −5.2 (c = 0.2, CHCl₃). IR (CHCl₃): ν_max = 3085, 2956, 2933, 2862, 1741, 1644, 1467, 1426, 1379, 1323, 1252, 1293, 1174, 1094, 991, 923, 886 cm⁻¹. ¹H NMR (400 MHz, CDCl₃/TMS): δ 6.00–5.86 (m, 1H), 5.77 (ddd, J = 17.3, 10.5, 6.5 Hz, 1H), 5.29–5.12 (m, 5H), 3.11 (td, J = 7.0, 1.3 Hz, 2H), 1.70–1.50 (m, 2H), 1.42–1.20 (m, 6H), 0.88 (t, J = 6.3 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 170.8, 136.5, 130.4, 118.5, 116.6, 75.1, 39.4, 34.1, 31.5, 24.7, 22.5, 14.0 ppm. HRMS: m/z calcd for C₁₂H₂₀O₂Na [M + Na]⁺ 219.1361; found 219.1351.

(S)-6-Pentyl-3,6-dihydro-2H-pyran-2-one (4). To a stirred and degassed solution of 12 (100 mg, 0.51 mmol) in dry CH₂Cl₂ (70 mL) was added Grubbs second-generation catalyst (4.3 mg, 0.005 mmol, 1.0 mol%) at room temperature and the mixture refluxed for 12 h. It was then cooled and filtered through a small pad of silica gel and the filtrate concentrated. The residue was purified by silica gel column chromatography using petroleum ether/EtOAc (6 : 1) as eluent to give 4 (82.3 mg, 96%) as colorless oil. [α]²⁵_D = +35.2 (c = 0.24, CHCl₃). IR (CHCl₃): ν_max = 2956, 2932, 2861, 1735, 1467, 1382, 1240, 1165, 1118, 1057, 829, 704 cm⁻¹. ¹H NMR¹⁶ (400 MHz, CDCl₃/TMS): δ 5.88–5.81 (m, 2H), 4.99–4.96 (m, 1H), 3.07–3.05 (m, 2H), 1.78–1.71 (m, 2H), 1.40–1.25 (m, 6H), 0.89 (t, J = 6.9 Hz, 3H) ppm. ¹³C NMR¹⁶ (100 MHz, CDCl₃): δ 169.2, 126.6, 121.4, 79.7, 35.6, 31.4, 29.9, 23.9, 22.5, 13.9 ppm.

(4R,5S)-4-Hydroxy-5-[(S)-1-hydroxyhexyl]dihydrofuran-2(3H)-one (1) from 4. To a mixture of K₃Fe(CN)₆ (0.942 g, 2.86 mmol, 3.0 equiv.), K₂CO₃ (0.396 g, 2.86 mmol, 3.0 equiv.), MeSO₂NH₂ (90.6 mg, 0.952 mmol, 1.0 equiv.), (DHQ)₂PHAL (7.6 mg, 0.0096 mmol, 1.0 mol%) and K₂OsO₄·2H₂O (1.4 mg, 0.0038 mmol, 0.4 mol%) were added t-BuOH (3 mL) and water (5 mL). The mixture was stirred for 5 min and cooled at 0 °C in ice bath. To the cooled mixture, a solution of the olefin 4 (160 mg, 0.952 mmol) in t-BuOH (2 mL) was added. The reaction mixture was stirred at 0 °C for 24 h and then quenched with solid Na₂SO₃ and stirred for 30 min. The solution was extracted with EtOAc (3 × 20 mL) and the combined organic layers were washed with 2 N KOH (10 mL), brine, dried (Na₂SO₄) and concentrated. The residue was purified by silica gel column chromatography using petroleum ether/EtOAc (1 : 1) as an eluent to give 1 (0.156 g, 71%) as a colorless oil. [α]²⁵_D = +4.7 (c = 0.1, MeOH). Spectral data is same as before.

Acknowledgements

We thank the Board of Research in Nuclear Sciences (BRNS), Grant no. 2013/37C/59/BRNS for financial support. P.H.P thanks University Grants Commission (UGC), New Delhi for research fellowship.

Notes and references

1. Z. Chen, P. Wu, Y. Huang, J. Xue and X. Wei, Nat. Prod. Res., 2006, 20, 1145.
2. (a) R. A. Fernandes and A. K. Chowdhury, Tetrahedron: Asymmetry, 2011, 22, 1114; (b) R. A. Fernandes and A. K. Chowdhury, Eur. J. Org. Chem., 2011, 1106; (c) R. A. Fernandes, M. B. Halle, A. K. Chowdhury and A. B. Ingle, Tetrahedron: Asymmetry, 2012, 23, 60; (d) R. A. Fernandes and P. Kattanguru, Asian J. Org. Chem., 2013, 2, 74; (e) R. A. Fernandes and M. B. Halle, Asian J. Org. Chem., 2013, 7, 593; (f) D. A. Chaudhari, P. Kattanguru and R. A. Fernandes, Tetrahedron: Asymmetry, 2014, 25, 1022; (g) R. A. Fernandes, P. H. Patil and A. K. Chowdhury, Eur. J. Org. Chem., 2014, 237; (h) R. A. Fernandes and P. Kattanguru, J. Org. Chem., 2012, 77, 9357.
3. (a) T. Katsuki and K. B. Sharpless, J. Am. Chem. Soc., 1980, 102, 5974; (b) Y. Gao, R. M. Hanson, J. M. Klunder, S. Y. Ko, H. Masamune and K. B. Sharpless, J. Am. Chem. Soc., 1987, 109, 5765; (c) A. Riera and M. Moreno, Molecules, 2010, 15, 1041; (d) A. Pfenninger, Synthesis, 1986, 2, 89.
4. (a) H. Becker and K. B. Sharpless, Angew. Chem., Int. Ed. Engl., 1996, 35, 448; (b) H. C. Kolb, M. S. VanNieuwenhze and K. B. Sharpless, Chem. Rev., 1994, 94, 2483; (c) K. B. Sharpless, W. Amberg, Y. L. Bennani, G. A. Crispino, J. Hartung, K.-S. Jeong, H.-L. Kwong, K. Morikawa, Z.-M. Wang, D. Xu and X.-L. Zhang, J. Org. Chem., 1992, 57, 2768.
5. (a) H. Rama Mohan and A. S. Rao, Org. Prep. Proced. Int., 1993, 25, 321; (b) J. Kiefl, G. Pollner and P. Schieberle, J. Agric. Food Chem., 2013, 61, 5226.
6. H. P. Acharya and Y. Kobayashi, Tetrahedron, 2006, 62, 3329.
7. (a) G. B. Payne, J. Org. Chem., 1962, 27, 3819; (b) J. S. Brimacombe and A. K. M. S. Kabir, Carbohydr. Res., 1986, 152, 329.
8. (a) G. Kumaraswamy and R. S. Kumar, Helv. Chim. Acta, 2013, 96, 1366; (b) I. Sanyal, P. D. Barman and A. K. Banerjee, Synthesis, 2012, 44, 1102.
9. (a) B. Neises and W. Steglich, Angew. Chem., Int. Ed. Engl., 1978, 17, 522; (b) B. Schmidt and O. Kunz, Eur. J. Org. Chem., 2012, 1008; (c) R. A. Fernandes, P. H. Patil and A. K. Chowdhury, Asian J. Org. Chem., 2014, 3, 58.
10. (a) R. H. Grubbs, S. J. Miller and G. C. Fu, Acc. Chem. Res., 1995, 28, 446; (b) A. Deiters and S. F. Martin, Chem. Rev., 2004, 104, 2199.
11. J. Wu, S. M. Cooper, R. J. Cox, J. Crosby, M. P. Crump, J. Hothersall, T. J. Simpson, C. M. Thomas and C. L. Willis, Chem. Commun., 2007, 2040.
12. K. J. Quinn, A. K. Isaacs and R. A. Arvary, Org. Lett., 2004, 6, 4143.
13. R. Doran and P. J. Guiry, Synthesis, 2014, 46, 761.
14. T. Sugiyama, M. Watanabe, T. Sassa and K. Yamashita, Agric. Biol. Chem., 1983, 47, 2411.
15. N. Kanbayashi and K. Onitsuka, Angew. Chem., Int. Ed., 2011, 50, 5197.
16. F. Caijo, F. Tripoteau, A. Bellec, C. Crévisy, O. Baslé, M. Mauduit and O. Briel, Catal. Sci. Technol., 2013, 3, 429.

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Footnote

† Electronic supplementary information (ESI) available: Copies of ¹H and ¹³C NMR spectra for all the compounds. See DOI: 10.1039/c5ra07930f

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