untitled European Journal of Chemistry 6 (1) (2015) 93‐97 European Journal of Chemistry ISSN 2153‐2249 (Print) / ISSN 2153‐2257 (Online)  2015 Atlanta Publishing House LLC ‐ All rights reserved ‐ Printed in the USA http://dx.doi.org/10.5155/eurjchem.6.1.93‐97.1150 European Journal of Chemistry Journal webpage: www.eurjchem.com Stereoselective total synthesis of pectinolide H and 4'‐epi‐pectinolide H Ramesh Perla and Nitin Wasantrao Fadnavis * Natural Products Chemistry Division, Indian Institute of Chemical Technology, Habsiguda, Hyderabad‐500007, India * Corresponding author at: Natural Products Chemistry Division, Indian Institute of Chemical Technology, Habsiguda, Hyderabad‐500007, India. Tel.: +91.40.27191631. Fax: +91.40.27160512. E‐mail address: fadnavis@iict.res.in (N.W. Fadnavis). ARTICLE INFORMATION ABSTRACT DOI: 10.5155/eurjchem.6.1.93‐97.1150 Received: 11 September 2014 Received in revised form: 13 October 2014 Accepted: 18 October 2014 Published online: 31 March 2015 Printed: 31 March 2015 The total synthesis of pectinolide H and 4'‐epi‐pectinolide H was accomplished with 27% yield in nine steps from inexpensive and commercially available compound, (+)‐diethyl tartrate ((+)DET)) by employing swern oxidation, Wittig olefination, Grignard and lactonization reactions. KEYWORDS Reduction Pectinolide H Lactonization Swern oxidation Wittig olefination Grignard reaction Cite this: Eur. J. Chem. 2015, 6(1), 93‐97 1. Introduction Pectinolide H (1) (Figure 1) isolated from aerial parts of a Mexican terrestrial plant Hyptis pectinata displays significant antimicrobial activity against a panel of multidrug‐resistant strains of Staphylococcus aureus [1]. The molecule possesses an α,β‐unsaturated γ‐lactone motif common to many natural products exhibiting antibacterial and anti‐inflammatory activities. Many compounds with similar structures have also been reported to be potentially useful as anticancer agents and enzyme inhibitors [2‐10]. Considering the importance of new antimicrobial agents for multidrug resistant microorganisms, synthesis of molecules such as Pectinolide H in a simple and straightforward manner is necessary. To the best of our knowledge, two reports exist for the synthesis of pectinolide H (1) [11,12]. Herein, we report an easy approach to compound 1 carried out in nine simple steps. Our synthetic strategy also provides the epimer 4'‐epi‐ pectinolide H (2). 2. Experimental All commercially available chemicals were purchased from Sigma Aldrich and used without purification. All experiments were carried out under an inert nitrogen atmosphere. 2.1. Instrumentation 1H and 13C NMR spectra were recorded on Bruker Avance 300 MHz and Bruker Avance 75 MHz spectrometers, respect‐ tively, using CDCl3 as solvent and SiMe4 as the internal standard. FT‐IR analyses were performed using Perkin Elmer RX1 FT‐IR spectrophotometer. Mass spectra analyses were performed on VG Auto spec instrument. Optical rotations were determined using Jasco Dip 360 digital polarimeter. 2.2. Synthesis 2.2.1. Synthesis of diethyl (4R,5R)‐2,2‐dimethyl‐1,3‐ dioxolane‐4,5‐dicarboxylate (7) A solution of compound 6 (10 g, 48.54 mmol), p‐toluene sulfonic acid (100 mg) in CH2Cl2 (100 mL) and 2,2‐ dimethoxypropane (12 mL, 97 mmol) was stirred at room temperature for 4 h. The reaction mixture was quenched with solid NaHCO3, filtered, solvent was evaporated under vacuum. The crude product was purified by flash column chroma‐ tography (Hexane:EtOAc, 98:2, v:v) to give compound 7. Color: Colorless liquid. Yield: 10.75 g, 90%. FT‐IR (Neat, ν, cm‐1): 2990, 1753, 1216. 1H NMR (300 MHz, CDCl3, δ, ppm): 1.31 (t, 6H, CH3‐CH2‐O), 1.50 (s, 6H, (CH3)2C), 4.27 (q, 4H, CH2‐OCO), 4.76 (s, 2H, CH‐COO). 94 Perla and Fadnavis / European Journal of Chemistry 6 (1) (2015) 93‐97 Figure 1. Structure of pectinolide A‐C, H and 4‐epi‐pectinolide H. EtO OEt O O O O (+)-DET HO OH O O TBDPSO OH O O RO O O OEt O RO O O + O OEt RO O O O H RO O O OH RO O O OAc HO O O OAc O O OAc O EtO OH O OAc O OH O OAc O + a b c d e f g h i j R=TBDPS 6 7 8 9 10a 10b 11 12 13 14 15 1 2 10a:10b = 80:20 Reagents and conditions: a) 2,2‐DMP, PTSA(cat.) CH2Cl2, rt, 4 h, 90 %. b) LiAlH4, THF, 0 °C to rt, 1 h, 85%. c) TBDPSCl, NaH, THF, 0 °C to rt, 2h, 90%. d) (i) (COCl)2, DMSO, CH2Cl2, Et3N, ‐78 °C. (ii) Ph3PCHCOOEt, MeOH, ‐50 °C to rt, (88% in two steps). e) DIBAL‐H, CH2Cl2, ‐78 °C, 30 min. f) Mg, nBuBr, THF, (66% in two steps). g) Ac2O, DMAP, Pyridine, CH2Cl2, rt, 3 h, 99%. h) TBAF, THF, rt, 5 h, 92%. i) (i) (COCl)2, DMSO, CH2Cl2, Et3N, ‐78 °C. (ii) (F3CCH2O)2POCH2COOEt, 18‐ crown ether, KHMDS, dry THF, ‐78 °C, 4 h, (80% in two steps). j) TsOH, MeOH, 2 h, 93%. Scheme 1 13C NMR (75 MHz, CDCl3, δ, ppm): 13.9, 26.2, 61.7, 76.9, 113.5, 169.5. ESI‐MS (m/z): 247 (M+1)+, 269 (M+Na)+. 2.2.2. Synthesis of ((4S,5S)‐2,2‐dimethyl‐1,3‐dioxolane‐4,5‐ diyl)dimethanol (8) A solution of compound 7 (6 g, 24.4 mmol) in THF (20 mL) was slowly added to a suspension of LiAlH4 (3.7 g, 97.5 mmol) in THF (100 mL) at 0 °C over a period of 20 min under nitrogen atmosphere. After 2 h, aqueous NH4Cl (10%, w:v, 20 mL) was added and the reaction mixture was filtered through celite. The filtrate was dried over anhydrous MgSO4 and evaporated under vacuum. The crude product was purified by flash column chromatography using EtOAc as eluent to afford pure compound 8 (Scheme 1). Color: Colorless liquid. Yield: 3.35 g, 85%. FT‐IR (Neat, ν, cm‐1): 3403. 1H NMR (300 MHz, CDCl3, δ, ppm): 1.43 (s, 6H, (CH3)2C), 2.77 (br. s, 2H, 2 ‐OH), 3.68‐3.81 (m, 4H, CH2‐OH), 3.98‐3.99 (m, 2H, CH‐CH2‐OH). 13C NMR (75 MHz, CDCl3, δ, ppm): δ 26.9, 62.0, 78.1, 109.2. ESI‐MS (m/z): 162 (M+). [α]D25: ‐8.16 (c 1, CHCl3). 2.2.3. Synthesis of ((4S,5S)‐5‐((tert‐butyldiphenylsilyloxy) methyl)‐2,2‐dimethyl‐1,3‐dioxolan‐4‐yl) methanol (9) To a stirred solution of diol (8) (1.62 g, 10 mmol) in anhydrous THF (50 mL), NaH (264 mg, 11 mmol) was added at 0 °C under nitrogen atmosphere and the contents were stirred for 30 min. A solution of tert‐butylchlorodiphenylsilane (TBDPS‐Cl) (2.74 g, 10 mmol) dissolved in anhydrous THF (20 mL) was added and stirring was continued for 2 h at room temperature. The reaction mixture was quenched with water (40 mL) and THF was evaporated. The residue was extracted with CH2Cl2 (3×10 mL), dried over anhydrous MgSO4, and concentrated under vacuum. The crude product was subjected to flash column chromatography (Hexane:EtOAc, 4:1, v:v) to afford compound 9 (Scheme 1). Color: Colorless oil. Yield: 3.6 Perla and Fadnavis / European Journal of Chemistry 6 (1) (2015) 93‐97 95 g, 90%. FT‐IR (Neat, ν, cm‐1): 3466, 2931, 1428, 1245, 1080, 702. 1H NMR (300 MHz, CDCl3, δ, ppm): 1.06 (s, 9H, (CH3)3C‐ Si), 1.38 (s, 3H, CH3‐C‐O), 1.41 (s, 3H, CH3‐C‐O), 3.63‐3.84 (m, 4H, CH2‐OH, CH2‐OSi), 3.93‐3.99 (m, 1H, CH‐CH2‐OH), 4.04‐ 4.10 (m, 1H, CH‐CH2‐OSi), 7.36‐7.43 (m, 6H, Ar‐H), 7.64‐7.68 (m, 4H, Ar‐H). 13C NMR (75 MHz, CDCl3, δ, ppm): 19.1, 26.7, 26.9, 27.0, 62.5, 64.1, 77.4, 79.5, 109.1, 127.7, 127.8, 129.8, 129.9, 132.8, 135.5. ESI‐MS (m/z): 423 (M+Na)+. [α]D25: ‐1.5 (c 14.5, CHCl3). 2.2.4. Synthesis of (Z)‐ethyl 3‐((4S,5S)‐5‐((tert‐butyl diphenylsilyloxy)methyl)‐2,2‐dimethyl‐1,3‐dioxolan ‐4‐yl) acrylate (10a) and (E)‐ethyl 3‐((4S,5S)‐5‐((tert‐butyl diphenylsilyloxy) methyl)‐2,2‐dimethyl‐1,3‐dioxolan‐4‐yl) acrylate (10b) To a solution of oxalyl chloride (0.7 mL, 8 mmol) in dry CH2Cl2 (20 mL), DMSO was added drop‐wise (1.14 mL, 16 mmol) at ‐78 °C over 20 min under nitrogen atmosphere and stirred for 30 min at the same temperature. To this reaction mixture, compound 9 (1.6 g, 4 mmol) in CH2Cl2 (5.0 mL) was added drop‐wise over 15 min at ‐78 °C, and resulting mixture was stirred for 3 h at same temperature. The reaction was quenched with Et3N (5.0 mL) and allowed to reach room temperature over 30 min. The solvent was removed on rotavapor and the residue was purified by a flash column chromatography (Hexane:EtOAc, 10:1, v:v) to obtain crude aldehyde which was employed in the next step immediately. The solution of crude aldehyde (1.52 g, 3.82 mmol) in MeOH (15 mL) was added to a solution of Ph3P=CHCOOEt (4 g, 11.5 mmol) in MeOH (100 mL) at ‐50 °C drop‐wise over 30 min. The resulting solution was stirred for 1 h at same temperature, diluted with water and extracted with CH2Cl2 (3×25 mL). The organic layer was dried over anhydrous MgSO4 and the solvent was removed under vacuum. The residue was purified by flash column chromatography (Hexane:EtOAc, 50:1, v:v) to obtain pure compounds 10a and 10b in 80:20 ratio (Scheme 1). (Z)‐Ethyl 3‐((4S,5S)‐5‐((tert‐butyldiphenylsilyloxy)methyl)‐ 2,2‐dimethyl‐1,3‐dioxolan ‐4‐yl)acrylate (10a): Color: Colorless oil. Yield: 1.32 g, 70%. FT‐IR (Neat, ν, cm‐1): 2932, 1720, 1111. 1H NMR (300 MHz, CDCl3, δ, ppm): 1.04 (s, 9H, (CH3)3C‐Si), 1.21 (t, 3H, CH3‐CH2‐O), 1.432 (s, 3H, CH3‐C‐O), 1.439 (s, 3H, CH3‐C‐O), 3.80‐3.88 (m, 3H, CH2‐OSi, CH‐CH2‐OSi), 4.07 (q, 2H, CH2‐OCO), 5.44‐5.52 (m, 1H, CH‐CH=CH), 5.86 (dd, 1H, J = 10.5, 1.5 Hz, HC‐COO), 6.12 (dd, 1H, J = 9.0, 3.0 Hz, HC=CH‐COO), 7.32‐7.43 (m, 6H, Ar‐H), 7.67‐7.69 (m, 4H, Ar‐H). 13C NMR (75 MHz, CDCl3, δ, ppm): 14.1, 19.1, 26.7, 27.0, 27.1, 60.3, 64.1, 73.4, 82.1, 117.0, 122.9, 127.5, 127.7, 129.5, 130, 135.6, 135.7, 145.3, (C=O not seen). ESI‐MS (m/z): 469 (M+1)+, 491 (M+Na)+. (E)‐Ethyl 3‐((4S,5S)‐5‐((tert‐butyldiphenylsilyloxy) methyl)‐ 2,2‐dimethyl‐1,3‐dioxolan‐4‐yl)acrylate (10b): Color: Colorless oil. Yield: 0.33 g, 18%. FT‐IR (Neat, ν, cm‐1): 2933, 1719, 1112. 1H NMR (300 MHz, CDCl3, δ, ppm): 1.07 (s, 9H, (CH3)3C‐Si), 1.29 (t, 3H, CH3‐CH2‐O), 1.4 (s, 3H, CH3‐C‐O), 1.44 (s, 3H, CH3‐C‐ O), 3.81‐3.88 (m, 3H, CH2‐OSi, CH‐CH2‐OSi), 4.20 (q, 2H, CH2‐ OCO), 4.57‐4.62 (m, 1H, CH‐CH=CH), 6.10 (dd, 1H, J = 15.8, 1.5 Hz, HC‐COO), 6.93 (dd, 1H, J = 10.5, 5.2 Hz, HC=CH‐COO ), 7.35‐ 7.43 (m, 6H, Ar‐H), 7.65‐7.70 (m, 4H, Ar‐H). 13C NMR (75 MHz, CDCl3, δ, ppm): 14.2, 19.1, 26.7, 26.9, 27.0, 60.4, 63.1, 77.4, 80.7, 109.8, 122.1, 127.5, 127.7, 129.5, 129.7, 132.8, 135.5, 135.7, 144.4, 165.9. ESI‐MS (m/z): 469 (M+1)+, 491 (M+Na)+. 2.2.5. Synthesis of (Z)‐1‐((4S,5S)‐5‐((tert‐butyldiphenylsilyl oxy)methyl)‐2,2‐dimethyl‐1,3‐dioxolan‐4‐yl)hept‐1‐en‐3‐ol (12) To a stirred solution of compound 10a (2.0 g, 4.27 mmol) in CH2Cl2 (50 mL), diisobutylaluminium hydride (DIBAL‐H) (2.48 mL, 4.27 mmol) was added drop‐wise at ‐78 °C, and the reaction mixture was stirred for 30 min at same temperature. The reaction was quenched with aqueous MeOH (10 mL, 50%, v:v) at 0 °C. Saturated sodium potassium tartrate solution (10 mL) was added and the contents were extracted with CH2Cl2. The combined organic layer was dried over anhydrous MgSO4, concentrated under vacuum to obtain the crude aldehyde 11 which was used in next step without further purification. A solution of n‐butyl bromide (0.92 mL, 8.54 mmol) in THF (5 mL) was added to a suspension of Mg (0.2 g, 8.33 mmol) in THF (30 mL) and refluxed for 20 min. The reaction mixture was cooled to 0 °C and solution of crude aldehyde 11 in THF (10 mL) was added. After 1 h the reaction was quenched with aqueous NH4Cl, filtered through a celite. The filtrate was dried anhydrous MgSO4, concentrated under vacuum, and purified by flash column chromatography (Hexane:EtOAc, 80:20, v:v) to afford diastereoisomeric mixture of compound 12 (Scheme 1). Color: Pale yellow oil. Yield: 1.36 g. 66%. FT‐IR (Neat, ν, cm‐1): 3441, 2931, 1428, 1113. 1H NMR (300 MHz, CDCl3, δ, ppm): 0.89 (t, 3H, CH3‐CH2‐), 1.06 (s, 9H, (CH3)3C‐Si), 1.23‐1.37 (m, 4H, CH2‐CH2‐CH3), 1.43 (s, 6H, (CH3)2C), 1.46‐1.53 (m, 2H, CH2‐ (CH2)2‐CH3), 3.69‐3.86 (m, 3H, CH2‐OSi, CH‐CH2‐OSi), 4.09 (q, 1H, CH(OH)), 4.43 (t, 1H, HC‐CH=), 5.65 (dd, 1H, J = 8.3, 6.7 Hz, =CH‐CH(OH)), 5.78 (dd, 1H, J = 9.8, 6.0 Hz, CH=CH‐CH(OH)), 7.35‐7.43 (m, 6H, Ar‐H), 7.65‐7.70 (m, 4H, Ar‐H). 13C NMR (75 MHz, CDCl3, δ, ppm): 13.9, 19.2, 22.5, 26.7, 26.9, 27.0, 27.4, 36.6, 62.7, 71.9, 78.0, 81.4, 109.0, 127.4, 127.6, 129.6, 129.7, 133.1, 135.6, 137.5. ESI‐MS (m/z): 505 (M+Na)+. HRMS calcd. for C29H42O4NaSi [M+Na]+: 505.27446, Found: 505.27282. 2.2.6. Synthesis of (Z)‐1‐((4S,5S)‐5‐((tert‐butyldiphenylsilyl oxy)methyl)‐2,2‐dimethyl‐1,3‐dioxolan‐4‐yl)hept‐1‐en‐3‐yl acetate (13) To a stirred solution of alcohol 12 (482 mg, 1.03 mmol) in CH2C12 (10 mL) were added catalytic amount (5 mg) of 4‐ dimethylaminopyridine (DMAP) and pyridine (0.126 mL, 1.55 mmol) at 0 °C. Under stirring at same temperature, acetic anhydride (0.147 mL, 1.55 mmol) was added and the resulting mixture was stirred for 3 h at room temperature. The reaction mixture was quenched with aqueous NaHCO3 solution (10%, w:v, 5 mL), and extracted with EtOAc. The organic layer was dried over anhydrous MgSO4, concentrated under vacuum, and purified by flash column chromatography (Hexane:EtOAc, 9:1, v:v) to afford compound 13 (Scheme 1). Color: Colorless oil. Yield: 0.54 g, 99%. FT‐IR (Neat, ν, cm‐1): 2932, 1740, 1238, 1113. 1H NMR (300 MHz, CDCl3, δ, ppm): 0.87 (t, 3H, CH3‐CH2‐ ), 1.06 (s, 9H, (CH3)3C‐Si), 1.20‐1.34 (m, 4H, CH2‐CH2‐CH3), 1.43 (s, 6H, (CH3)2C), 1.51‐1.65 (m, 2H, CH2‐(CH2)2‐CH3), 2.05 (s, 3H, CH3‐CO), 3.68‐3.84 (m, 3H, CH2‐OSi, CH‐CH2‐OSi), 4.44‐4.50 (m, 1H, HC‐CH=), 5.21‐5.27 (m, 1H, CH(OAc)), 5.68‐5.72 (m, 2H, CH=CH), 7.35‐7.43 (m, 6H, Ar‐H), 7.65‐7.70 (m, 4H, Ar‐H). 13C NMR (75 MHz, CDCl3, δ, ppm): 13.8, 19.1, 21.1, 22.3, 26.7, 26.8, 26.9, 27.1, 33.9, 62.5, 73.5, 77.8, 81.2, 109, 127.6, 129.4, 129.6, 131.9, 133.0, 135.5, 170. ESI‐MS (m/z): 547 (M+Na)+. HRMS calcd. for C31H44O5SiNa [M+Na]+: 547.2964, Found: 547.2954. 2.2.7. Synthesis of (Z)‐1‐((4S,5S)‐5‐(hydroxymethyl)‐2,2‐ dimethyl‐1,3‐dioxolan‐4‐yl)hept‐1‐en‐3‐yl acetate (14) To a stirred solution of compound 13 (945 mg, 1.8 mmol) in dry THF (20 mL), TBAF (5.45 mL, 1 M in THF, 5.41 mmol) was added at room temperature and the resulting solution was stirred for 5 h. The solvent was evaporated under vacuum and purified by flash column chromatography (Hexane:EtOAc, 6:1, v:v) to afford compound 14 (Scheme 1). Color: Colorless oil. Yield: 0.493 g, 92%. FT‐IR (Neat, ν, cm‐1): 3451, 2934, 2873, 1738, 1240, 1048. 1H NMR (300 MHz, CDCl3, δ, ppm): 0.89 (t, 3H, CH3‐CH2), 1.25‐1.36 (m, 4H, CH2‐CH2‐CH3), 1.43 (s, 6H, (CH3)2C), 1.59‐1.63 (m, 2H, CH2‐(CH2)2‐CH3), 2.04 (s, 3H, CH3‐ CO), 3.55‐3.85 (m, 3H, CH2‐OH, CH‐CH2‐OH), 4.32 (m, 1H, HC‐ CH=), 5.25 (m, 1H, CH(OAc)), 5.63‐5.83 (m, 2H, CH=CH). 13C 96 Perla and Fadnavis / European Journal of Chemistry 6 (1) (2015) 93‐97 NMR (75 MHz, CDCl3, δ, ppm): 13.8, 21.2, 22.3, 26.90, 26.99, 27.2, 33.9, 60.5, 73.6, 77.2, 81.0, 109.3, 129.1, 133.3, 170.3. ESI‐MS (m/z): 287 (M+1)+, 309 (M+Na)+. HRMS calcd. for C15H27O5 [M+H]+: 287.1781, Found: 287.1652. 2.2.8. Synthesis of (Z)‐ethyl 3‐((4S,5S)‐5‐((Z)‐3‐acetoxyhept‐ 1‐enyl)‐2,2‐dimethyl‐1,3‐dioxolan‐4‐yl)acrylate (15) To a stirred solution of (COCl)2 (0.25 mL, 2.8 mmol) in dry CH2Cl2 (30 mL) was added anhydrous DMSO (0.4 mL, 5.6 mmol) at ‐78 °C over a period of 20 min under nitrogen atmosphere, and the reaction mixture was stirred for 30 min. A solution of compound 14 (400 mg, 1.4 mmol.) in CH2Cl2 was added and the resulting solution was stirred for 1 h at ‐78 °C. The reaction was quenched with Et3N (1.17 mL, 8.4 mmol), allowed to reach room temperature and then extracted with CH2Cl2. The combined organic layer was dried over anhydrous MgSO4 and evaporated under vacuum to obtain crude aldehyde which was employed to the next step immediately. To a stirred solution of (F3CCH2O)2POCH2COOEt (0.354 mL, 1.67 mmol), 18‐crown‐6 (1.478 g, 5.6 mmol) in dry THF (2 mL) at ‐78 °C was added KHMDS (0.362 g, 1081 mmol) and stirred for 30 min. The solution of crude aldehyde in THF (5 mL) was added, reaction mixture was stirred for 4 h at same temperature. The reaction was quenched with saturated aqueous NH4Cl (5 mL) and extracted with ethyl acetate. The combined organic layers were dried over anhydrous MgSO4, concentrated under vacuum, and the residue was purified by flash column chromatography (Hexane:EtOAc, 8:2, v:v) to afford compound 15 (Scheme 1). Color: Colorless oil. Yield: 0.396 g, 80%. FT‐IR (Neat, ν, cm‐1): 2937, 1725, 1371, 1234, 1048. 1H NMR (300 MHz, CDCl3, δ, ppm): 0.88 (t, 3H, CH3‐ (CH2)2), 1.25‐1.31 (m, 7H, ((CH2)2‐CH3, CH3‐CH2‐O), 1.45 (s, 6H, (CH3)2C), 1.53‐1.66 (m, 2H, CH2‐(CH2)2‐CH3), 2.0 (s, 3H, CH3‐ CO), 4.03‐4.22 (m, 3H, O‐CH2‐CH3, CH‐CH=CH), 5.22‐5.30 (m, 1H, CH‐CH=CH‐COO), 5.38‐5.46 (m, 1H, CH(OAc)), 5.71‐5.76 (m, 2H, CH=CH‐CH(OAc)), 5.93 (d, 1H, J = 11.3 Hz, CH‐COOEt), 6.12 (dd, 1H, J = 8.3, 3.0 Hz, HC=CH‐COOEt). 13C NMR (75 MHz, CDCl3, δ, ppm): 13.8, 14.0, 21.1, 22.3, 26.9, 27.01, 27.06, 33.8, 60.2, 73.2, 75.8, 81.4, 109.8, 123.3, 127.9, 133.2, 143.8, 164.9, 170.0. ESI‐MS (m/z): 377 (M+Na)+. HRMS calcd. for C19H30O6Na [M+Na]+: 377.2042, Found: 377.1987. 2.2.9. Synthesis of pectinolide H (1) and 4‐epi‐pectinolide H (2) A solution of compound 15 (25 mg, 0.706 mmol) in MeOH (10 mL) was stirred with a catalytic amount of PTSA (2 mg) at room temperature. After 4 h MeOH was evaporated and the crude product was purified by preparative thin layer chromatography (Hexane: EtOAc, 1:1, v:v) to obtain pure compounds 1 and 2 in 1.2 : 1 ratio (Scheme 1). (1S,4S,Z)‐1‐hydroxy‐1‐((S)‐5‐oxo‐2,5‐dihydrofuran‐2‐yl)oct‐ 2‐en‐4‐yl acetate (Pectinolide H) (1): Color: Colorless oil. Yield: 9.6 mg, 50.8 %. FT‐IR (Neat, ν, cm‐1): 3439, 2931, 2862, 1750, 1241, 1042. 1H NMR (300 MHz, CDCl3, δ, ppm): 0.89 (t, 3H, CH3‐(CH2)2), 1.22‐1.36 (m, 4H, (CH2)2‐CH3), 1.50‐1.70 (m, 2H, CH2‐(CH2)2‐CH3), 2.06 (s, 3H, CH3‐CO), 3.07 (br. 1H, OH), 4.28‐ 4.33 (m, 1H, CH‐OH), 5.00‐5.04 (m, 1H, CH(OAc)), 5.15‐5.22 (m, 1H, CH‐CH=CH‐COO), 5.62‐5.84 (m, 2H, CH=CH‐CH(OAc)), 6.19 (dd, 1H, J = 4.5, 1.5 Hz, =CH‐COO), 7.47 (dd, 1H, J = 6.7, 1.5 Hz, CH=CH‐COO). 13C NMR (75 MHz, CDCl3, δ, ppm): 13.8, 21.1, 22.2, 27.0, 33.7, 72.2, 73.7, 85.5, 122.9, 128.4, 133.2, 153.2, 170.5, 172.6. ESI‐MS (m/z): 291 (M+Na)+. [α]D25: ‐39.0 (c 0.32, CHCl3). HRMS calcd. for C14H20O5Na [M+Na]+: 291.1202; Found: 291.1200. (1S,4R,Z)‐1‐hydroxy‐1‐((S)‐5‐oxo‐2,5‐dihydrofuran‐2‐yl)oct‐ 2‐en‐4‐yl acetate (4‐epi‐pectinolide H) (2): Color: Colorless oil. Yield: 8 mg, 42.3%. FT‐IR (Neat, ν, cm‐1): 3444, 2928, 2856, 1750, 1241, 1043. 1H NMR (300 MHz, CDCl3, δ, ppm): 0.89 (t, 3H, CH3‐(CH2)2), 1.24‐1.31 (m, 4H, (CH2)2‐CH3), 1.54‐1.68 (m, 2H, CH2‐(CH2)2‐CH3), 2.06 (s, 3H, CH3‐CO), 2.76 (br. 1H, OH), 4.27‐4.30 (m, 1H, CH‐OH), 4.99‐5.01 (m, 1H, CH(OAc)), 5.18‐ 5.24 (m, 1H, CH‐CH=CH‐COO), 5.64‐5.84 (m, 2H, CH=CH‐ CH(OAc)), 6.18 (d, 1H, J = 4.7 Hz, =CH‐COO), 7.43 (dd, 1H, J = 5.7, 4.7 Hz, CH=CH‐COO). 13C NMR (75 MHz, CDCl3, δ, ppm): 13.8, 21.2, 22.3, 27.1, 33.8, 72.5, 73.7, 85.5, 123.0, 128.3, 133.5, 153.1, 170.5, 172.5. ESI‐MS (m/z): 291 (M+Na)+. [α]D25: +21.9 (c 0.1, CHCl3). HRMS calcd. for C14H20O5Na [M+Na]+: 291.1202, Found: 291.1188. 3. Results and discussion A cursory look at the structure of compound 1 shows that (+)‐diethyl L‐tartrate (6) possesses the required (2S,3S)‐ stereochemistry. Protection of the vicinal hydroxy groups as an acetonide and reduction of compound 7 with LiAlH4 gave the corresponding diol (8) in 85% yield. Selective mono‐ protection of compound 8 was achieved with 1 equiv. of (tert‐ butyl diphenylsilyl chloride (TBDPSCl) in presence of NaH in THF. The mono protected alcohol (9) was oxidized to the corresponding aldehyde by Swern oxidation. The crude aldehyde was subjected to Wittig olefination in methanol to obtain a mixture of E and Z‐alkene (10) with E to Z ratio of 20:80. The isomers were easily separated by column chromatography [13]. Reduction of the ester group of Z‐(10a) with DIBAL‐H in CH2Cl2 and Grignard reaction of the aldehyde (11) with n‐butyl magnesium bromide gave a diastereo‐ isomeric mixture of secondary alcohols (12). Acetylation with Ac2O in pyridine provided a mixture of diastereomers (13). Deprotection of the primary alcohol with TBAF followed by Swern oxidation of the alcohol (14) gave an intermediate aldehyde which was subjected to Still‐Gennari olefination reaction [14,15] without isolation to afford the corresponding α,β‐unsaturated ester (15) in 80% yield. Deprotection of the acetonide and subsequent in situ lactonization of ester (15) with p‐toluenesulfonic acid in MeOH afforded a diastereomeric mixture of pectinolide H (1) and 4'‐epi‐pectinolide H (2) in 98% yield (Scheme 1). Both the diastereomers were separa‐ ted by preparative TLC. The 1H and 13C NMR spectral data and optical rotation of pectinolide H were in excellent agreement with the data previously reported in literature [11,12]. 4. Conclusion In conclusion, a simple stereoselective total synthesis of pectinolide H and 4'‐epi‐pectinolide H have been achieved from (+)‐DET in nine steps with 27% overall yield. 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