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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: kita@che.kyutech.ac.jp
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: kita@che.kyutech.ac.jp
,
Shuhei Takahashi
a   Department of Applied Chemistry, Kyushu Institute of Technology, 1-1 Sensuicho, Tobata, Kitakyushu, 804-8550, Japan   Email: kita@che.kyutech.ac.jp
,
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: kita@che.kyutech.ac.jp
,
Mitsuru Kitamura*
a   Department of Applied Chemistry, Kyushu Institute of Technology, 1-1 Sensuicho, Tobata, Kitakyushu, 804-8550, Japan   Email: kita@che.kyutech.ac.jp
› Author AffiliationsThis 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)

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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.

Key words

diazonapthoquinone - rhodium - eleutherol - eleuthoside A - glycosidation - intramolecular cyclization - 1 Introduction - 2 Results and Discussion - 2.1 Synthetic Strategy - 2.2 Synthesis of Aglycone, Eleutherol - 2.3 Glycosidation and Synthesis of Eleuthoside A - 3 Conclusions

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    Supporting information for this article is available online at https://doi.org/10.1055/s-0036-1589118.
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  • References and Notes

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