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Synlett 2012; 23(19): 2845-2849
DOI: 10.1055/s-0032-1317491
DOI: 10.1055/s-0032-1317491
letter
Toward a Total Synthesis of Divergolide A; Synthesis of the Amido Hydro- quinone Core and the C10–C15 Fragment
Further Information
Publication History
Received: 20 August 2012
Accepted after revision: 26 September 2012
Publication Date:
09 November 2012 (online)
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Abstract
A ring-closing metathesis (RCM) approach was envisioned for installing the E double bond at the C9 and C10 positions of divergolide A, isolated from a mangrove endophyte. Accordingly, the C10–C15 diene diol fragment and the amido hydroquinone core with the requisite functionalities and stereochemistry have been synthesized by using the norephedrine-based syn-selective glycolate aldol and the anti-selective aldol reactions, respectively. CuI-catalyzed amidation was employed to access the anilide intermediate, which was further transformed into the amido hydroquinone core.
Key words
-
aldol reactions -
selectivity -
natural products -
hydroquinone -
total synthesis
Supporting Information
- for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
- Supporting Information
-
References and Notes
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- 18 Synthesis of Quinone 24 via Oxidation of Phenol 23: To a solution of phenol 23 (257.0 mg, 0.55 mmol) in MeCN (4 mL) at r.t. was quickly added an aqueous solution of 2,6-DCPFC (334 mg in 1.1 mL H2O, 1.1 mmol), prepared according to the literature procedure.17a After stirring for 1 min, the reaction was quenched by addition of saturated aqueous NaHCO3. The reaction mixture was extracted with EtOAc (10 × 3 mL) and the combined organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (SiO2; EtOAc–petroleum ether, 1:40) to give quinone 24 (209.3 mg, 79% yield) as a yellow solid. Mp 80–81 °C (CH2Cl2–pentane); [α]D 20 +53.60 (c 1.10, CHCl3); Rf = 0.40 (EtOAc–petroleum ether, 2.4%). IR (film): 3380, 3296, 2957, 2925, 2854, 1714, 1650, 1606, 1502, 1255, 1099 cm–1. 1H NMR (400 MHz, CDCl3): δ = 8.06 (br s, 1 H, NH), 7.50 (d, J = 2.8 Hz, 1 H), 6.70 (dd, J = 2.0, 1.2 Hz, 1 H), 4.73 (d, J = 4.8 Hz, 1 H), 3.57 (dd, J = 10.0, 5.6 Hz, 1 H), 3.44 (dd, J = 10.0, 5.2 Hz, 1 H), 2.22 (s, 3 H), 1.94–1.91 (m, 1 H), 0.90 (s, 9 H), 0.89 (d, J = 6.0 Hz, 3 H), 0.81 (s, 9 H), 0.06 (s, 3 H), –0.05 (s, 3 H), –0.07 (s, 3 H), –0.09 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 188.2, 182.6, 169.1, 148.2, 138.1, 133.3, 114.5, 69.1, 63.5, 42.4, 25.8 (3×), 25.8 (3×), 24.8, 18.3, 18.0, 14.2, –4.6, –5.2, –5.5, –5.6. HRMS (EI+): m/z [M+] calcd for C24H43NO5Si2: 481.2680; found: 481.2682.
- 19 Synthesis of Hydroquinone 25 via Reduction of 24: To a yellow solution of quinone 24 (144.5 mg, 0.30 mmol) in a mixed solvent of THF–Et2O–H2O (6 mL; v/v/v = 1:1:1) at r.t., was added Na2S2O4 (525 mg, 3 mmol) in portions with vigorous stirring until the yellow color of the mixture disappeared. The reaction mixture was diluted with H2O (5 mL) and extracted with EtOAc (5 × 3 mL). The combined organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (SiO2; EtOAc–petroleum ether, 1:3) to give hydroquinone 25 (145.2 mg, 99% yield) as a colorless oil. Rf = 0.50 (EtOAc–PE, 33%). [Note: Hydroquinone 25 was oxidized to quinone in air during acquisition of 13C NMR data. No optical rotation data was taken for this sample]. 1H NMR (400 MHz, CDCl3): δ = 8.19 (s, 1 H, NH), 8.10 (s, 1 H, OH), 7.91 (s, 1 H, OH), 7.55 (s, 1 H), 6.32 (s, 1 H), 4.84 (d, J = 6.0 Hz, 1 H), 3.61 (dd, J = 9.6, 4.4 Hz, 1 H), 3.43 (dd, J = 9.2, 7.2 Hz), 2.34 (s, 3 H), 2.15–2.07 (m, 1 H), 0.94 (s, 9 H), 0.89 (s, 9 H), 0.74 (d, J = 6.8 Hz, 3 H), 0.11 (s, 3 H), 0.9 (s, 6 H), –0.05 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 169.3, 149.7, 137.0, 126.9, 126.0, 109.8, 106.2, 64.7, 60.4, 42.4, 25.9 (4×), 25.7 (3×), 24.8, 18.3, 18.1, –5.1, –5.3 (2×), –5.5. HRMS (EI+): m/z [M+] calcd for C24H45NO5Si2: 483.2836; found: 483.2834.
For selected reviews on RCM, see:
For a review, see:
Fremy’s salt (potassium nitrosodisulfonate) was not available to us and it was not tested in the oxidation of 23. For recent examples, see: