Stereoselective synthesis of the C79–C97 fragment of symbiodinolide

Summary Symbiodinolide is a polyol marine natural product with a molecular weight of 2860. Herein, a streamlined synthesis of the C79–C97 fragment of symbiodinolide is described. In the synthetic route, a spiroacetalization, a Julia–Kocienski olefination, and a Sharpless asymmetric dihydroxylation were utilized as the key transformations.

General methods.Reagents were used as received from commercial suppliers unless otherwise indicated.All reactions were carried out under an atmosphere of argon.
Reaction solvents were purchased as dehydrated solvents and stored with active molecular sieves 4 Å under argon prior to use for reactions.All solvents for work-up procedures were used as received.Analytical thin-layer chromatography (TLC) was performed with aluminium TLC plates (Merck TLC silica gel 60F 254 ).Column chromatography was performed with Fuji Silysia silica gel BW-300 or Kanto Chemical silica gel 60N.Optical rotations were recorded on a JASCO DIP-1000.IR spectra were recorded on a JASCO FT/IR-460 plus. 1 H and 13 C NMR spectra were recorded on JEOL JNM-AL400.Chemical shifts are reported in ppm with reference to the internal residual solvent ( 1 H NMR, CHCl 3 7.26 ppm, C 6 H 6 7.15 ppm; 13 C NMR, CDCl 3 77.0ppm, C 6 D 6 128.0 ppm).The following abbreviations are used to designate the multiplicities: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad.Coupling constants (J) are in hertz.High-resolution mass spectra were recorded on a Micromass
The resulting mixture was added to CuI (1.67 g, 8.80 mmol) at −50 °C and the mixture was stirred for 5 min at the same temperature.To the resulting mixture was added a solution of epoxide 13 (8.40 g, 41.5 mmol) in THF (40 mL + 5.0 mL + 5.0 mL) at −78 °C.After the mixture was stirred for 1 h at the same temperature, the mixture was warmed to room temperature over 2 h.The reaction was quenched with saturated aqueous NH 4 Cl.The resulting mixture was diluted with hexane/EtOAc (5:1) solution, washed with H 2 O and brine, and then dried over Na 2 SO 4 .Concentration gave the corresponding alcohol (10.7 g), which was used for the next step without further purification.
Concentration gave the corresponding alkane (36.9 mg), which was used for the next step without further purification.
To a solution of the alcohol obtained above (112 mg) in CH 2 Cl 2 (1.9 mL) were added imidazole (36.0 mg, 0.529 mmol) and TBSCl (68.4 mg, 0.454 mmol) at room temperature.After the mixture was stirred for 30 min at the same temperature, the Alkene (E)-26.LDA was prepared by adding n-BuLi (1.57M solution in hexane, 0.54 mL, 0.845 mmol) to a solution of diisopropylamine (0.12 ml, 0.845 mmol) in THF (0.6 mL) at 0 °C.The solution was stirred for 30 min at 0 °C.