KEVIN DESISTO, PH.D

KEVIN DESISTO, PH.D

KEVIN DESISTO, PH.D

Kevin DeSisto’s entire Synthesis, Characterization, and Analysis of Proline Templacted Amino Acids Dissertation is presented on these Thesis pages as a viewable and downloadable PDF.

View and Download (or Print) here> 

The first ten pages of the Thesis Chapter 5 are also presented as web text below with accompanying illustrations. The Part 1 and Part 2 sections also have the first ten pages (with illustrations) of the Thesis Chapters 1 and 3.

Kevin DeSisto’s entire Synthesis, Characterization, and Analysis of Proline Templacted Amino Acids Dissertation is presented on these Thesis pages as a viewable and downloadable PDF.

View and Download (or Print) here>   

The first ten pages of the Thesis Chapter 5 are also presented as web text below with accompanying illustrations. The Part 1 and Part 2 sections also have the first ten pages (with illustrations) of the Thesis Chapters 1 and 3.

CHAPTER 5 – EXPERIMENTAL SECTION

EXPERIMENTAL METHODS

All reactions were run under an inert atmosphere of nitrogen (dried through DRIERITEÒ tube), unless otherwise noted. NMR spectra were collected using a Bruker ARX-500 MHz instrument. Chemical shifts are reported as parts per million downfield from tetramethylsilane (d) Infrared spectra were collected using a Perkin-Elmer System 2000 FT-IR spectrophotometer. Samples were prepared as thin films on NaCl disks. Low resolution mass spectra were obtained using a Finnegan 4610 quadrupole mass spectrometer, using isobutene for chemical ionization (CI) analysis at 100 eV. High-resolution mass spectra were obtained and performed by Washington University Resource for Biomedical and Bioorganic Mass Spectrometry (St Louis, MO). Flash chromatography performed with 120-mesh silica gel and thin layer chromatography (TLC) with Merck 60 PF 254 silica gel plates. Staining solutions include ninhydrin (3% in EtOH w/ 0.3% AcOH), phosphomolybdic acid (PMA) (2% in EtOH), and an iodine chamber as needed. Atlantic Microlabs (Norcross, GA) performed microanalysis. HPLC was performed in-lab using RP (C8/C18) silica gel, and Chiracel AD columns on an analytical scale and RP (C18) on a semi preparative scale (Rannin SD-200). Anhydrous solvents and reagents were stored under nitrogen and transferred via syringe or cannula. Tetrahydrofuran (THF) was distilled from sodium-benzophenone. acetonitrile (ACN), dichloromethane (DCM), trimethylamine (TEA), and xylenes were distilled from calcium hydride. Other anhydrous solvents such as diethyl ether, dimethylsulfoxide (DMSO), dimethylformamide (DMF) and trimethylorthoformate were purchased as such, and if applicable stored over 3Å molecular sieves under nitrogen.

Section 5.1 – 3-Substititued PTAAs

5.1.1 – Norleucine Series

tert-Butyl(4S,5S)-5-[(2,2-dimethyl-1,1diphenyl-silapropoxy)methyl]-2-oxo-4-propylpyrrolidinecarboxylate

(2.1): A 2.0M solution of propyl magnesium chloride in Et2O (33.2 mL, 66.4 mmol) was added to a suspension of copper(I)bromide.dimethylsulfide complex (6.89 g, 33.2 mmol) in dry Et2O (25 mL0 at -20 oC. After 15 min, a solution of (2.0) (3.00 g, 6.64 mmol) with TMS-Cl (1.69 mL, 13.3 mmol) in THF (25 mL) was added to the above solution ay -20 oC. After 30 min, the reaction was quenched with 10% aqueous NH4Cl (25 mL) and allowed to warm to room temperature, split, and the organic layer washed with 10% aqueous NH4Cl until the blue color disappeared in the washings (4 * 50 mL). The aqueous layer is backwashed with Et2O (50 mL) and the organic layers arecombined, dried (Na2SO4), and concentrated to a yellow oil. Flash chromatography on silica gel (6:1 hexanes:ethyl acetate) yields (2.1) (2.96 g, 5.96 mmol, 90%) as a colorless oil: [a]25D = -23.8o (c = 0.46 CHCl3); 1H NMR (CDCl3, 500 MHz) d 7.66-7.60 (m, 4H), 7.47-7.36 (m, 6H), 3.91-3.84 (m, 2H), 3.73 (d, J = 3.7 Hz, 1H), 2.91 (dd, J = 8.9, 18.1 Hz, 1H), 2.31 (m, 1H), 2.18 (m, 1H), 1.55-1.42 (s, 10H), 1.42-1.31 (m, 3H), 1.08 (s, 9H), 0.94 (t, J = 7.0 Hz, 3H); 13C NMR (CDCl3, 125 MHz) 175.4, 150.9, 136.7, 133.4 132.7, 129.0, 128.2, 83.3 64.1 38.8, 37.2, 33.0, 28.1, 27.8, 21.0, 19.4, 14.6 ppm; IR (film) 2959, 2930, 2858, 1696, 1394, 1112 cm-1; MS (CI) m/z 496 (MH), 440, 396, 260, 92. Anal. Calcd for C29H41NO4Si: C, 70.26; H, 8.34; N, 2.83. Found C, 70.17; H, 8.40; N, 2.80.

tert-Butyl(2S,3S)-2-[(2,2-dimethyl-1,1diphenyl-silapropoxy)methyl]-3-propylpyrrolidinecarboxylate

(2.2):A 1.0 M solution of lithium triethylborohydride in THF (7.17 mL, 7.17 mmol) in THF (15 mL) at -78 oC. After 30 min, the reaction mixture is quenched with 10% aqueous NH4Cl (25 mL) and allowed to warm to 0 oC. Then 30% H2O2 (0.3 mL) is added and the resulting mixture is allowed to stir at 0 oC for 20 min followed by extraction with ethyl acetate (3 * 5 mL). The organic layers are combined and washed with HO followed by aqueous saturated NaCl (5 mL), then dried over Na2SO4. Evaporation gives the crude hemiaminal as a pale yellow oil (3.36 g), which is carried on without purification. A solution of the crude hemiaminal and triethylsilane (1.05 mL, 6.57 mmol) in DCM (10 mL) is cooled to -78 oC, boron trifluoride etherate (832 mL, 6.57 mmol) is then added dropwise. After 20 min, an additional aliquot of triethylsilane (1.05 mL, 6.57 mmol) and BF3.OEt2 (832 mL, 6.57 mmol) is added at -78 oC. After 2h the reaction is quenched with saturated aqueous NaHCO3 (7 mL) and allowed to warm to room temperature. The layers are separated and the aqueous layer is then extracted with DCM (2 * 5 mL). The organic layers are combined, dried (Na2SO4), and concentrated. Flash chromatography on silica gel (7:1 hexanes:ethyl acetate) yields (2.2) (1.81 g,3.76 mmol, 63%) as a colorless oil: [a]25D = -24.8o (c = 0.86 CHCl3); 1H NMR (CDCl3, 500 MHz) d 7.67-7.58 (m, 4H), 7.45-7.33 (m, 6H), 3.91 (sb, 0.4H), 3.68 (m, 1H), 3.45 (m, 1H), 3.25 (m, 1H), 2.38 (sb, 0.6H), 2.30 (sb, 0.4H), 1.99 (dt, J = 7.2, 5.0 Hz 1H), 1.49-1.23 (m, 14H), 1.06 (s, 9H), 0.98-0.86 (m, 3H); 13C NMR (CDCl3, 125 MHz) 154.3, 135.3, 133.4, 129.4, 127.4 78.8, 78.5, 64.0, 63.7, 63.0, 45.1, 45.4, 40.5, 39.5, 36.1, 29.7, 28.8, 28.2, 26.6, 20.8, 19.0, 13.9 ppm; IR 9film) 2959, 2931, 2859, 1696 cm-1; MS (CI) m/z 482 (MH), 426, 368, 212, 156, 112. Anal. Cacld for C29H43NO3Si: C, 72.30; H, 9.00; N, 2.90. Found C, 72.17; H, 8.98; N, 2.92.

tert-Butyl(2S,3S)-2-(hydroxymethyl)-3-propylpyrrolidinecarboxylate

(2.3):A 1.0 M solution of TBAF in THF (13.3 mL, 13.3 mmol) is added to a solution of 2.2 (902 mg, 3.71 mmol) in THF (10 mL) at ambient temperature and allowed to react for 12 h. The reaction is diluted with ethyl acetate (20 mL) and washed with 10% aqueous NH4Cl (3 * 20 mL), dried (Na2SO4), and evaporate to a crude orange oil. Flash chromatography on silica gel (4:1 hexanes:ethyl acetate) yields (2.3) (803 mg,3.30 mmol, 89%) as a colorless oil: [a]25D = -19.2o (c = 0.57 CHCl3); 1H NMR (CDCl3, 500 MHz) d 4.96 (sb, 1H), 3.65 (m, 1H), 3.56-3.47 (m, 3H), 3.17 (m, 1H), 1.90 (m, 1H), 1.67 (m, 1H), 1.43 (s, 9H), 1.41-1.32 (m, 2H), 1.32-1.21 (m 3H), 0.88 (t,J= 7.1 Hz, 3H); 13C NMR (CDCl3, 125 MHz) 157.1, 80.2, 67.3, 66.1, 46.6, 41.4, 35.6, 30.1, 28.5, 21.0, 14.1 ppm: IR (film) 3423, 1696, 1670 cm-1;MS (CI) m/z 244 (MH), 212, 188, 156, 112

(2S,3S)-1-[(tert-butly)oxycarbonyl)]-3-propylpyrrolidine-2-carboxylic acid

(2.4): The alcohol 2.3 (150 mg, 0.616 mmol), sodium chlorite (139 mg, 1.23 mmol), and TEMPO (7.0 mg, 0.043 mmol) are dissolved (acetonitrile:NaH2PO4 [0.7 M] aqueous 3:2) (1.5 mL) and warmed to 35 oC. Sodium hypochlorite (bleach, 5.95% aq) (17 mL, 0.012 mmol) is then added via syringe and allowed to react for 2-4 h at 35 oC. The reaction is quenched into a cold, aqueous solution of sodium bisulfite (0.3 M, 5 mL) and extracted with ethyl acetate (3 * 3 mL). The organic layer are combined, dried (NaSO4), and concentrated. The crude acid is dissolved in ethyl acetate (3 mL) and extracted with a solution of saturated aqueous NaHCO3 (2 * 4 mL). The NaHCO3 solution is acidified with 12M HCl (1.0 mL) and extracted with ethyl acetate (3 * 4 mL). The organic layers are combined, dried (Na2SO4), and concentrated to yield 2.4 (138 mg,.0.536 mmol, 87%) as a white solid: mp 88 oC;  [a]25D = -33.0o (c = 1.56 CHCl3); 1H NMR (CDCl3, 500 MHz) d 10.73 (sb, 1H), 3.92 (d, J = 4.58 Hz, 0.4H), 3.78 (d, J = 5.99 Hz, 0.6H), 3.55 (m, 0.6H), 3.48-3.33 (m, 1.4H), 2.30 (m, 0.4H), 2.24  (m, 0.6H), 1.67 (m, 1H), 2.02 m, 1H), 1.59-1.47 (m, 2H), 1.42 (s 3.6H),1.37 (s, 5.4H), 1.34-1.28 (m, 3H), 0.88 (t, J = 7.7 Hz, 3H); 13C NMR (CDCl3, 125 MHz) 179.0, 177.3, 155.2, 154.0, 80.5, 80.4, 64.7, 64.3, 46.0, 45.7, 44.6, 42.9, 35.6, 30.3, 30.0, 28.4, 28.3, 20.7, 13.9 ppm; IR (film)3149, 2963, 1701, 1653 cm-1; MS (CI)m/z 258 (MH),202, 156, 112; Anal. Cacld for C13H23NO4 C, 60.68; H, 9.01; N, 5.44. Found C, 60.69; H, 9.03; N, 5.39.

Phenylmethyl(2S,3S)-1-[(tert-butly)oxycarbonyl)]-3-propylpyrrolidine-2-carboxylate

(2.13):The acid (2.4) (103 mg, 0.40 mmol) and DMAP (49 mg, 0.40 mmol) are dissolved in dissolved in DCM (15 mL) and diisopropylcarbodiimde (DIC) (95mL 0.62 mmol) is added dropwise followed by benzyl alcohol (62 mL, 0.62 mmol). After 3h, the reaction mixture was loaded directly on a silica gel column (hexanes:ethyl acetate, 5:1) to yield 2.13 (116 mg 0.33 mmol, 83%) as a colorless oil: ;  [a]25D = -23.8o (c = 0.63, CHCl3); 1H NMR (CDCl3, 500 MHz) d 742-7.24 (m, 5H), 5.28 (d, J = 12.5 Hz, 0.6H), 5.16 (s, 1H) 5.08 (d, J = 12.4 Hz, 0.4H), 4.00 (d, J = 5.3 Hz, 0.4H), 3.86 (d,J = 5.9 Hz, 0.6H), 3.63-3.56 (m, 0.7H), 3.35-3.40 (m, 1.3H), 2.19 (m, 1.3H), 2.03 (m, 1H), 1.59-1.48  (m, 3H), 1.43 (s, 3H), 1.41-1.32 (m,8H),0.88 (t, J = 7.2 Hz, 3H); 13C NMR (CDCl3, 125 MHz) 173.1, 172.8, 154.4, 153.8, 136.0, 135.7, 128.5, 128.4, 128.3, 128.0, 79.9, 79.7, 66.5, 64.9, 64.4, 45.9, 45.7, 44.5, 43.3, 35.6, 30.4, 29.9, 28.4, 28.2, 20.7, 13.8; IR 9film) 2961, 2844, 1750, 1700 cm-1; MS (CI) m/z 348 (MH), 292, 248, 212, 156, 112, 91. Anal. Cacld for C20H29NO4 C, 70.26; H, 8.34; N, 2.83. Found C, 70.17; H, 8.40; N, 2.80.

Section 5.1.2 – Leucine PTAA Oliomers

Phenylmethyl(2S,3S)-1-({(2S,3S)-1-[(tert-butyl)oxycarbonyl]-3-propylpyrrolidin-2-yl}carbonyl)-3-propylpyrrolidine-2-carboxylate

(2.15): The ester 2.13 (96 mg, 0.28 mmol) is treated with TFA (1.5 mL) and the resulting mixture is stirred at room temperature for 30 min. TFA is evaporated and the residue is dried in vacuo  for 1 h. In a separate flask, DIC (53 mL, 0.34 mmol) is added to a solution of 2.4 (71 mg, 0.28 mmol), DMAP (34 mg, 0.28 mmol), and 1-hydroxybenzotriazole (HOBt) (45 mg, 0.34 mmol) in DCM (2 mL). After 30 min, the activated ester is transferred via syringe to the HCl salt 2.14 followed by addition of TEA (75mL, 0.84 mmol). The reaction is maintained at room temperature for 8 h, then concentrated. Flash chromatography on silica gel (2:1 hexanes:ethyl acetate) yields 2.15 (99 mg.203 mmol, 73%) as a clear oil: [a]25D = -21.7o (c = 0.29 CHCl3); 1H NMR (500 MHz, CDCl3) d 7.38-7.2 (m, 5H), 5.25 (dd, J = 7.1, 5.2 Hz, 1H), 5.06 (dd, J = 6.4, 5.9 Hz, 1H), 4.22-4.16 (m, 1.6H), 4.04 (d, J = 4.27 Hz, 0.4H), 3.95 (m, 1H), 3.77 (m, 1H), 3.59-3.46 (m, 2.5H), 3.39 (m, 0.5H), 2.21-2.16 (m, 2H), 2.14 (m, 1H), 2.08 (m, 1H), 1.69 (m, 1H), 1.64-1.56 (m, 1.5H), 1.54-1.46 (m, 1.5H), 1.44 (s, 4.8H), 1.39 (s, 4.2H), 1.37-1.24 (m, 6H), 0.92-0.85 (m, 6H); 13C NMR (125 MHz, CDCl3) 172.1, 171.8, 171.5, 171.3, 154.7, 153.8 ppm; IR (film) 2961, 2932, 2844, 1750, 1700, 1398, 1165 cm-1; MS (CI) m/z 487 (MH) 431, 387, 212, 156, 112, 92. Anal. Cacld for C28H42N2O5 C, 69.11; H, 8.70; N, 5.76. Found C, 67.89; H, 8.75; N, 5.83.

Phenylmethyl(2S,3S)-1-({(2S,3S)-1-[(tert-butyl)carbonyl]-3-propylpyrrolidin-2-yl}carbonyl)-3-propylpyrrolidine-2-carboxylate

(2.16): The N-Boc dimer 2.15 (70 mg, 0.14 mmol) is stirred in TFA (1.5 mL) for 1 h at room temperature. The reaction is concentrated and dried under high vacuum. The resulting TFA salt is dissolved in DCM followed by addition of pivaloylchloride (19 mL, 0.15 mmol) and then TEA (38 mL, 0.42 mmol) is added and allowed to react for 6 h.  After 30 min, the activated ester is transferred via syringe to the HCl salt 2.14 followed by addition of TEA (75mL, 0.84 mmol). Purification via flash chromatography on silica gel (3:1 hexanes:ethyl acetate) yields 2.16 (64 mg.140 mmol, 97%) as a colorless oil: [a]25D = -23.0o (c = 0.26 CHCl3); 1H NMR (500 MHz, CD3OD) d 7.3-7.32 (m, 5H), 5.21 (d, J = 12.2 Hz, 1H), 5.19 (d, J = 12.3 Hz, 1H), 4.28 (d, J = 5.9 Hz, 1H), 4.10 (d, J = 6.6 Hz, 1H), 4.05 (m, 1H), 3.90 (m, 1H), 3.72 (m, 1H), 3.56 (m, 1H), 2.22-2.10 (m, 2H), 2.06 (m, 1H), 1.75 (m, 1H), 1.64-1.55 (m, 3H), 1.43-1.36 (m, 3H), 1.36-1.27(m, 3H), 1.24 (s, 9H), 0.91-0.87 (m, 6H); 13C NMR (125 MHz, CDCl3) 177.4, 773.1, 172.5, 136.7, 129.1, 128.8, 128.7, 66.9, 65.5, 64.8, 47.8, 46.8, 42.8, 40.8, 38.8, 35.7, 35.2, 31.5, 31.4, 27.4, 20.8, 20.7, 14.0, 13.8ppm; IR (film) 2961, 2932, 1750, 1746, 1699 cm-1; MS (CI) m/z 472 (MH) 224, 196, 112, 91. Anal. Cacld for C28H42N2O4 C, 71.46; H, 8.99; N, 5.95. Found C, 71.12; H, 9.02; N, 5.89.

(2S,3S)-1-({(2S,3S)-1-[(tert-butyl)carbonyl]-3-propylpyrrolidin-2-yl}carbonyl)-3-propylpyrrolidine-2-carboxylic acid

(2.17): Palladium on carbon (Pd/C, 10%) (5.6 mg, 5.0 mmol) is suspended in a solution of 2.16 (25 mg, 5.3 mmol) in ethyl acetate (1.0 mL) at room temperature. The mixture is subjected to hydrogen pressure (~20 psi, triple balloon) in a 50 mL RBF with stirring. After 3 h, the Pd/C is removed via Celite filtration and concentrated to a colorless oil, 2.17, in quantitative yield. (21 mg, 5.3 mmol, 100%): [a]25D = -23.8o (c = 0.60 CHCl3); 1H NMR (500 MHz, CHCl3) d 9.21 (b, 1H), 4.34 (d, J = 4.8 Hz, 1H), 4.19 (d, J = 6.7 Hz, 1H), 4.07 (m, 1H), 3.84-3.75 (m, 2H), 3.50 (m, 1H), 2.41 (m, 1H), 2.29-2.20 (m, 2H), 2.15 (m, 1H), 1.76 (m, 1H), 1.68-1.58 (m, 2H), 1.54 (m, 1H), 1.44-1.29 (m, 7H), 1.25 (s, 9H), 0.92 (t,J = 6.9, 6H); 13C NMR (125 MHz, CDCl3) 177.1, 174.1, 172.5, 65.3, 64.8, 47.7, 42.0, 38.6, 35.4, 34.8, 31.4, 31.1, 27.2, 20.8, 14.0, 13.9: IR (film) 3237, 2959, 2928, 2873, 2855, 1720, 1649, 1609 cm-1: MS (CI) m/z381.3 (MH) 337.0, 224.2, 196.2, 112.2, 84.2; Anal. Cacld for C21H36N2O4 C, 66.28; H, 9.54; N, 7.36. Found C, 65.15; H, 9.50; N, 7.31.

TRIMER

(2.18): The synthesis of 2.18 is accomplished from 2.17 (22 mg, 63 mmol) from 2.13 (35 mg, 57 mmol, 91%): [a]25D = -13.2o (c = 0.54 CHCl3); 1H NMR (500 MHz, CD3OD) d 7.46-7.30 (m, 5H), 5.21 (d, J = 12.2 Hz, 1H), 5.09 (d, J = 12.2 Hz, 1H), 4.34 (d, J = 6.46Hz, 1H), 4.04 (m, 1H), 3.99 (m, 1H), 3.89 (m, 1H), 3.72 (m, 1H), 3.64-3.51 (m, 2H), 2.24-2.09 (m, 6H), 1.74-1.66  (m, 3H), 1.66-1.56 (m, 3H), 1.42-1.31 (m, 8H), 1.31-1.27 (m, 1H), 1.24 (s, 9H), 0.95 (t, J = 7.5, 3H); 13C NMR (125 MHz, CDCl3) 177.1, 171.8, 170.8, 170.7, 128.2, 127.9,  65.2, 64.3, 62.9, 47.1, 46.4, 46.2, 42.4, 41.9, 40.0, 38.5, 34.9, 31.1, 30.7, 30.0, 27.2, 20.6, 20.5, 13.9, 13.8: IR (film) 2958, 2931, 2872, 1745, 1652, 1622, 1432, 1408, 1167 cm-1: MS (HRFAB, 3-NBA/Li)) m/z616.4285 (M+Li, -2.7 ppm).

Section 5.1.3 – Glutamic Acid PTAAs

Phenylmethyl-2-{(2S,3R)-2-[2,2-dimethyl-1,1-diphenyl-1-silapropoxy)methyl]-1-[tert-butyl)oxycarbonyl]-5-oxopyrrolidin-3-yl} propane-1,3-dioate

(2.7): Dibenzyl malonate (314 mg, 1.10 mmol) was added to a suspension of NaH (24.0 mg, 1.0 mmol) in acetonitrile (ACN) (2.5 mL) at room temperature. After 10 min, 2.0 (500 mg, 1.10 mmol) is ACN (2 mL) is added to the enolate via syringe pump over 6 h. The reaction is quenched with sat NH4Cl (5 mL) and extracted with ethyl acetate (3 * 4 mL). The organic layers are dried (Na2SO4) and concentrated to yield a viscous orange oil (877 mg). The crude oil is purified via flash chromatography on silica gel (6:1 hexanes:ethyl acetate), which yields 2.7 (674 mg.916 mmol, 83%) as a viscous, orange oil: [a]25D = -13.7o (c = 0.29 CHCl3); 1H NMR (500 MHz, CDCl3) d 7.63-7.48 (m, 4H), 7.45-7.33 (m, 6H), 5.17-5.12 (m, 3H), 5.06 (d, J = 12.1Hz, 1H), 4.05 (s, 1H), 3.92 (dd, J = 2.8, 10.6 Hz, 1H), 3.71 (dd, J = 1.6, 10.8 Hz, 1H), 3.57 (m, 1H), 3.10-3.02 (m, 2H), 2.34 (m, 1H), 1.42 (s, 9H), 1.02 (s, 9H); 13C NMR (125 MHz, CDCl3) 172.8, 167.5, 149.5, 135.5, 143.8, 134.7, 132.8, 132.5, 129.8, 128.6, 128.5, 128.4, 128.2, 127.8, 82.9, 67.6, 67.5, 65.0, 62.2, 55.4, 36.9, 33.5, 28.0, 26.8, 19.1, 14.2 ppm; IR (film) 1787, 1751, 1733 cm-1; MS (CI) m/z736 (MH); Anal. Cacld for C43H49NO8Si: C, 70.18; H, 6.71; N, 1.90. Found C, 70.03; H, 6.84; N, 1.90.

Phenylmethyl-2-{(2S,3R)-2-[2,2-dimethyl-1,1-diphenyl-1-silapropoxy)methyl]-1-[tert-butyl)oxycarbonyl]pyrrolidin-3-yl} propane-1,3-dioate

(2.8): A 1.0 M solution of BH3.THF in THF (7.64 mL, 7.64 mmol) is added via syringe to a stirring solution of 2.7 (2.25 g, 3.06 mmol) in DCM (20 mL) at room temperature. After 4.5h, the solution is quenched with 10% NH4Cl (7.5 mL). The layers are split and aqueous layer extracted with DCM (2 * 2.5 mL). The organic layers are combined, dried (Na2SO4), and concentrated to yield a colorless, crude oil (2.32 g).  Upon flash chromatography on silica gel (6:1 hexanes:ethyl acetate), 2.8 is isolated as a colorless oil(1.61 g.2.2 mmol, 73%): 1H NMR (500 MHz, CDCl3) d 7.64 (m, 4H), 7.47-7.21 (m, 16H), 5.22-5.08 (m, 4H), 4.01 (m, 0.4H), 3.83 (m, 0.6H), 3.76 (m, 0.8H),  3.71 (m, 1.2H), 3.67-3.53 (m, 2H), 3.39 (m, 1H), 3.17 (m, 1H), 2.26 (m, 1H), 1.68 (m, 1H), 1.49 (s, 3.6H), 1.31 (s, 5.4H), 1.07 (s, 9H), 1.03 (m, 1H); 13C NMR (125 MHz, CDCl3) 168.2, 168.0, 154.1, 135.6, 135.3, 133.6, 133.4, 133.2, 130.0, 129.8, 128.7, 128.6, 128.4, 128.3, 128.2, 128.0, 127.8, 79.5, 79.2, 73.8, 67.3, 65.0, 64.3, 63.6, 62.1, 61.8, 55.1, 55.0, 52.7, 45.9, 45.3, 41.4, 40.9, 40.3, 28.5, 28.0, 27.0, 19.2 ppm; IR (film) 2960, 2931, 2858, 1735,1694 cm-1; MS (CI) m/z 722.9 (MH).

KEVIN DESISTO

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