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Synlett 2025; 36(10): 1413-1417
DOI: 10.1055/a-2542-3481
DOI: 10.1055/a-2542-3481
letter
Total Synthesis of Aloin by Regioselective Diels–Alder Reactions Connecting Two 3-Silylbenzynes and a 2-Stannylfuran
This work was supported by the Research Support Project for Life Science and Drug Discovery [Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)] from AMED (Grant Number JP24ama121054) (for Y.S. and S.A.) and JST SPRING (Grant Number JPMJSP2138) (for S.M.).
Abstract
The first synthesis of aloin, a natural anthrone C-glycoside, was achieved through two sequential Diels–Alder (DA) reactions connecting two 3-silylbenzynes and a 2-stannylfuran. The silyl and stannyl substituents contributed to the regioselectivity of the two DA reactions and the 9,10-ether cleavage of the DA adduct. Subsequent conversion of the silyl groups into hydroxy groups and a C10-glycosylation completed the synthesis of aloin.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-2542-3481.
- Supporting Information
Publication History
Received: 29 December 2024
Accepted after revision: 19 February 2025
Accepted Manuscript online:
19 February 2025
Article published online:
01 April 2025
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- 20 Aloin (4) A brown test tube was charged with 24 (13 mg, 20 μmol), capped with a septum, and evacuated and purged with Ar ten times. 1 M aq NaOH (2.0 mL, 2 mmol) was added, and the mixture was stirred for 15 min at RT. 1 M aq HCl (3.0 mL) was added from a syringe under an Ar atmosphere at 0 ℃, and the resulting mixture was extracted with EtOAc. The combined organic layers were washed with brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography [silica gel, EtOAc–MeOH (20:1)] to afford a yellow solid; yield: 7.8 mg (19 μmol, 95%; 1:1 mixture of two diastereomers at the C10 position); mp 113–115 ℃. IR (NaCl): 3377, 2922, 2853, 1637, 1617, 1602, 1571 cm–1. 1H NMR (500 MHz, CD3OD): δ = 7.50 (t, J = 7.9 Hz, 1 H), 7.49 (t, J = 8.5 Hz, 1 H), 7.10–7.07 (m, 4 H), 6.89–6.86 (m, 4 H), 4.66–4.62 (m, 6 H), 3.58 (dd, J = 10.9, 1.8 Hz, 1 H), 3.56 (dd, J = 10.9, 1.8 Hz, 1 H), 3.42 (dd, J = 10.9, 1.8 Hz, 2 H), 3.40–3.36 (m, 2 H), 3.26 (td, J = 8.7, 1.8 Hz, 2 H), 3.03 (t, J = 9.4 Hz, 1 H), 3.01 (t, J = 9.2 Hz, 1 H), 2.95–2.89 (m, 4 H). 13C NMR (150 MHz, DMSO-d 6): δ = 193.41, 193.39, 161.1, 160.94, 160.91, 160.8, 152.2, 151.4, 145.9, 145.7, 142.1, 141.8, 136.1, 135.3, 120.3, 118.9, 117.8, 117.4, 117.1, 116.2, 115.82, 115.76, 115.7, 115.4, 112.7, 112.3, 85.2, 85.1, 80.9, 80.8, 78.22, 78.16, 70.3, 70.23, 70.21, 70.1, 62.41, 62.37, 61.4 (2C), 44.2, 43.9. HRMS (MALDI): m/z [M + Na]+ calcd for C21H22NaO9: 441.1156; found: 441.1151.
For a review on the isolation, see:
For structure determination, see:
For the synthesis of aloe-emodin (1), see: