Chemical Properties
Colorless Oil
Uses
An intermediate of Leustroducsin B (LSN-B), a novel colony-stimulating factor (CSF) inducer, which was isolated from Streptomyces platensis.
Synthesis
Synthesis of Intermediate IV: Porcine liver esterase (PLE, 51.2 mg, 1382 units) was added to a stirred suspension of methyl 3-cyclohexene-1-carboxylate (III, 5.19 g, 37.0 mmol) in pH 7.00 phosphate buffer solution (520 mL, 0.07 M). The pH of the reaction system was maintained at 7.00 by dropwise addition of NaOH solution (1.0 M) via syringe pump.The reaction was stirred continuously at room temperature until 1 equivalent of NaOH (37 mL) was consumed (reaction time: 11 h, TLC monitoring of the unfolding agent: petroleum ether/ether, 1:1). The reaction mixture was transferred to a dispensing funnel and washed twice with ethyl acetate (2 × 300 mL). After separating the phases, the organic phase was back-extracted twice with pH 7.00 phosphate buffer solution (2 × 300 mL). The aqueous phases were combined and acidified to pH 2 with aqueous HCl (30 mL, 4 M), followed by three extractions with ethyl acetate (3 × 400 mL). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure (100 mbar). The crude product was filtered through a short silica gel column to afford (R)-3-cyclohexenecarboxylic acid (IV) as a light yellow oil (3.92 g, 84% yield). The enantiomeric excess values of the product were 96.3% ee (GC assay), 94.3% ee (spin assay), [α]D21 +89.12° (c = 6.730, methanol) (literature value: +94.5° (c = 7, methanol), [Acta Chem. Scand., 1970, 24, 2693]).
References
[1] Patent: US2008/161546, 2008, A1. Location in patent: Page/Page column title page; 18
[2] Chemistry - A European Journal, 2012, vol. 18, # 5, p. 1342 - 1351
[3] Patent: US2008/200406, 2008, A1. Location in patent: Page/Page column 25; sheet 1
[4] Patent: US2011/251148, 2011, A1. Location in patent: Page/Page column 9
[5] Patent: WO2012/61662, 2012, A1. Location in patent: Page/Page column 60
