Synlett 2018; 29(04): 457-462
DOI: 10.1055/s-0036-1589118
letter
© Georg Thieme Verlag Stuttgart · New York

Total Synthesis of Eleuthoside A; Application of Rh-Catalyzed Intramolecular Cyclization of Diazonaphthoquinone

Dina I. A. Othman
a  Department of Applied Chemistry, Kyushu Institute of Technology, 1-1 Sensuicho, Tobata, Kitakyushu, 804-8550, Japan   Email: [email protected]
b  Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
,
Kota Otsuka
a  Department of Applied Chemistry, Kyushu Institute of Technology, 1-1 Sensuicho, Tobata, Kitakyushu, 804-8550, Japan   Email: [email protected]
,
Shuhei Takahashi
a  Department of Applied Chemistry, Kyushu Institute of Technology, 1-1 Sensuicho, Tobata, Kitakyushu, 804-8550, Japan   Email: [email protected]
,
Khalid B. Selim
b  Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
,
Magda A. El-Sayed
b  Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
,
Atif S. Tantawy
b  Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
,
Tatsuo Okauchi
a  Department of Applied Chemistry, Kyushu Institute of Technology, 1-1 Sensuicho, Tobata, Kitakyushu, 804-8550, Japan   Email: [email protected]
,
Mitsuru Kitamura*
a  Department of Applied Chemistry, Kyushu Institute of Technology, 1-1 Sensuicho, Tobata, Kitakyushu, 804-8550, Japan   Email: [email protected]
› Author Affiliations
This work was supported by JSPS KAKENHI Grant Number 26410054.
Further Information

Publication History

Received: 27 August 2017

Accepted after revision: 20 September 2017

Publication Date:
03 November 2017 (online)


Abstract

The first total synthesis of (±)-eleutherol and eleuthoside A, the natural cytotoxic substances extracted from medicinal Indonesian plant, is described. First, the synthesis of (±)-eleutherol has been ­accomplished in nine steps starting from bromo methoxy aldehyde with the aid of diazo-transfer chemistry approach. Second, a metal-­catalyzed intramolecular cyclization reaction of the corresponding ­diazonaphthoquinone led to the desired eleuotherol, which served as a precursor to eleuthoside A. Then, several glycosidation routes, using different glucosyl donors, were experimented to reach effective O-glycosidation of eleutherol. The only successful strategy involved Koenigs–Knorr glycosidation using peracetyl glycosyl bromide in the presence of Ag2O and quinoline. This strategy furnished our desired acetylated glycoside of β-configuration, regioselectively. Finally, deacetylation and successive separation of diastereomers were conducted to give eleuthoside A.

Supporting Information

 
  • References and Notes

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  • 22 Experimental Procedure and Physical Data of Eleuthoside A (1) The solid of peracetyl glycoside 20 (8.0 mg, 0.1 mmol) was dissolved in MeOH (2 mL), and then, K2CO3 (4.8 mg, 0.25 mmol) was added. The reaction mixture was stirred at room temperature until TLC showed complete conversion of starting material (1 h). Then, the reaction mixture was concentrated under reduced pressure and purified by PTLC eluting with (CHCl3/MeOH, 6:1) to afford (1.5 mg, 20%) eleuthoside A (1) as a single isomer along with 28% mixed isomer with the ratio 1/3-epi-1 (3:1) and 8% mixed isomer with the ratio 1:1. The spectral data of the white crystals of the natural isomer will be detailed below Mp 210 °C. Rf = 0.42 (CHCl3/MeOH, 6:1), [α]D –58.6 (c 0.0015, in MeOH at 25 °C). 1H NMR (500 MHz, CD3OD): δ = 8.22 (s, 1 H, H-9), 7.68 (d, 1 H, J = 8.0 Hz, H-8), 7.54 (dd, 1 H, J = 7.9, 8.0 Hz, H-7), 7.15 (d, 1 H J = 7.9 Hz, H-6), 6.07 (q, 1 H, J = 6.6 Hz, H-3), 5.01 (d, 1 H, J = 7.6 Hz, H-1′), 4.02 (s, 3 H, OCH3), 3.72 (dd, 1 H, J = 2.1, 11.6 Hz, H-6B′), 3.61 (dd, 2 H, H-2′, H-6A′), 3.49 (dd, 1 H, J = 9.2, 9.5 Hz, H-3′), 3.42 (dd, 1 H, J = 9.4, 9.5 Hz, H-4′), 3.12 (ddd, 1 H, J = 2.1, 5.8, 9.4 Hz, H-5′), 1.74 (d, 3 H, J = 6.6 Hz, 3-CH3). 1 H NMR (500 MHz, CDCl3): δ = 8.27 (s, 1 H, H-9), 7.68 (d, 1 H, J = 8.0 Hz, H-8), 7.53 (dd, 1 H, J = 7.9, 8.0 Hz, H-7), 7.10 (d, H J = 7.9 Hz, H-6), 5.91 (q, 1 H, J = 6.6 Hz, H-3), 4.95 (d, 1 H, J = 7.6 Hz, H-1′), 4.02 (s, 3 H, OCH3), 3.82 (s, 2 H, br OH), 3.78–3.72 (m, 2 H, J = 7.4, 9.5 Hz, H-6B′, H-6A′), 3.68 (d, 2 H, H-2, H-4′, J = 8.8, 9.5 Hz), 3.49 (dd, 1 H, J = 9.2, 9.5 Hz, H-3′), 3.12 (ddd, 1 H, J = 4.5, 8.8, 9.0 Hz, H-5′), 2.84 (s, 1 H, br-OH), 2.73 (s, 1 H, br-OH), 1.73 (d, 3 H, J = 6.5 Hz, 3-CH3). 13C NMR (125 MHz, CD3OD): δ = 170.9, 156.0, 146.4, 139.3, 138.0, 127.06, 124.5, 122.6, 122.6, 122.3, 108.3, 104.7, 79.5, 76.9, 76.4, 74.6, 70.1, 61.0, 54.7, 17.9. IR (ATR): 3404 (OH), 2971, 1750 (C=O), 1586, 1033 cm–1. HRMS (ESI+): m/z = 429 [M + Na+]; calcd for C20H22NaO9: 429.1162; found: 429.1154.
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