Synlett 2019; 30(20): 2285-2289
DOI: 10.1055/s-0039-1690249
letter
© Georg Thieme Verlag Stuttgart · New York

Enantioselective Total Synthesis of Ligraminol D and Ligraminol E

Baliram B. Mane
,
D. D. Kumbhar
,
Department of Chemistry, Savitribai Phule, Pune University (Formerly University of Pune), Ganeshkhind, Pune 411007, India   Email: suresh@chem.unipune.ac.in
› Author Affiliations
Savitribai Phule Pune University (Ref. No. O.S.D./B.C.U.D./83); Council of Scientific and Industrial Research [09/137(0560)/2016-EMR-I to B.B.M.
Further Information

Publication History

Received: 13 September 2019

Accepted after revision: 21 October 2019

Publication Date:
30 October 2019 (online)

Abstract

As a part of our ongoing research on the synthesis of bioactive constituents or molecules by using an organocatalytic approach, enantioselective total syntheses of ligraminol D and ligraminol E were achieved starting from a commercially available nonchiral aldehyde. Key steps in this synthesis were an asymmetric α-aminoxylation of an aldehyde and a Mitsunobu reaction.

Supporting Information

 
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  • 18 4-{(2R)-3-Hydroxy-2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]propyl}-2-methoxyphenol (Ligraminol E) (5) To a solution of ether 16 (0.190 g) in MeOH (10 mL) was added 10% Pd/C (0.05 g), and the mixture was stirred for 12 h under H2 (150 psi; 1.03 MPa). The catalyst was filtered off and the filtrate was concentrated under reduced pressure. A solution of the resulting crude ether (0.154 g, 0.30 mmol) in anhyd THF (5 mL) was added dropwise to a cold (0 °C) suspension of LiAlH4 (0.025 g, 0.66 mmol) in anhyd THF (5 mL), and the suspension as stirred for 3 h at rt, then cooled to 0 °C. The reaction as quenched with sat. aq NH4Cl (2 mL), and mixture was diluted with EtOAc (10 mL), filtered through a Celite pad under vacuum, and concentrated under reduced pressure. The crude product was purified by column chromatography [silica gel, EtOAc–hexane (3:7)] to give a sticky colourless liquid; yield: 0.119 g (93%; two steps); [α]D 25 +17.5 (c 0.103, MeOH) [Lit.11b +18.3 (c 0.10, MeOH)]. IR (neat): 3387, 2923, 2852, 1602, 1509, 1261, 1026, 798 cm–1. 1H NMR (400 MHz, CDCl3): δ = 6.87–6.83 (m, 1 H), 6.81–6.76 (m, 3 H), 6.74–6.69 (m, 2 H), 4.24–4.18 (m, 1 H), 3.87 (s, 3 H), 3.86 (s, 3 H), 3.71–3.63 (m, 4 H), 3.06 (dd, J = 13.9, 6.7 Hz, 1 H), 2.90 (dd, J = 13.9, 6.9 Hz, 1 H), 2.66 (t, J = 6.9 Hz, 2 H), 1.91–1.84 (m, 2 H). 13C NMR (101 MHz, CDCl3): δ = 150.9, 146.5, 145.6, 144.3, 137.3, 129.7, 122.1, 121.0, 119.8, 114.4, 112.4, 112.2, 85.14, 63.4, 62.1, 55.9, 55.8, 37.3, 34.2, 31.8. HRMS (ESI, +): m/z [M + Na]+ calcd for C20H26NaO6: 385.1627; found: 385.1628. (2S)-3-(3,4-Dimethoxyphenyl)-2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]propan-1-ol (Ligraminol D) (4) A solution of ether 19 (0.115 g, 0.23 mmol) in anhyd THF (5 mL) was added dropwise to a cold (0 °C) suspension of LiAlH4 (0.018 g, 0.48 mmol) in dry THF (5 mL) and the suspension was stirred for 3 h at r.t, then cooled to 0 °C. The reaction was quenched with sat. aq NH4Cl (3 mL), and the mixture was diluted with EtOAc (10 mL), filtered through a Celite pad under vacuum, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel, 25% EtOAc–hexane) to give a sticky liquid; yield: 0.077 g (93%), [α]D 25 –24.3 (c 0.154, MeOH); {Lit.11b –29.0 (c 0.1, MeOH); Lit.11a +9.5 (c 0.1, MeOH)} IR (neat): 3402, 2945, 1605, 1510, 1036 cm 1. 1H NMR (400 MHz, CDCl3): δ = 6.82 (br s, 3 H), 6.76 (br s, 1 H), 6.68 (d, J = 0.9 Hz, 2 H), 4.25–4.19 (m, 1 H), 3.88 (s, 3 H), 3.87 (s, 3 H), 3.86 (s, 3 H), 3.69–3.67 (m, 4 H), 3.08 (dd, J = 13.9, 6.7 Hz, 1 H), 3.01–2.88 (m, 2 H), 2.66 (t, J = 6.7 Hz, 2 H), 1.91–1.84 (m, 2 H). 13C NMR (101 MHz, CDCl3): δ = 150.9, 148.9, 147.7, 145.5, 137.3, 130.5, 121.5, 121.0, 119.8, 112.8, 112.4, 111.3, 85.1, 63.5, 62.1, 55.9, 55.9, 55.9, 37.3, 34.2, 31.8. HRMS (ESI, +): m/z [M + Na]+ calcd for C21H28NaO6: 399.1784; found: 399.1781.