Synthesis 2014; 46(07): 879-886
DOI: 10.1055/s-0033-1340663
paper
© Georg Thieme Verlag Stuttgart · New York

Synthesis of a Dihydropyranonucleoside Using an Oxidative Glycosylation Reaction­ Mediated by Hypervalent Iodine

Hiroya Kan-no
a  Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan   Fax: +81(22)2752013   Email: yoshimura@tohoku-pharm.ac.jp
,
Yukako Saito
a  Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan   Fax: +81(22)2752013   Email: yoshimura@tohoku-pharm.ac.jp
,
Shun Omoto
a  Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan   Fax: +81(22)2752013   Email: yoshimura@tohoku-pharm.ac.jp
,
Sakie Minato
a  Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan   Fax: +81(22)2752013   Email: yoshimura@tohoku-pharm.ac.jp
,
Hideaki Wakamatsu
a  Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan   Fax: +81(22)2752013   Email: yoshimura@tohoku-pharm.ac.jp
,
Yoshihiro Natori
a  Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan   Fax: +81(22)2752013   Email: yoshimura@tohoku-pharm.ac.jp
,
Tomozumi Imamichi
b  Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA
,
Hiroki Takahata*
a  Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan   Fax: +81(22)2752013   Email: yoshimura@tohoku-pharm.ac.jp
,
Yuichi Yoshimura*
a  Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan   Fax: +81(22)2752013   Email: yoshimura@tohoku-pharm.ac.jp
› Author Affiliations
Further Information

Publication History

Received: 11 December 2013

Accepted after revision: 27 December 2013

Publication Date:
05 February 2014 (eFirst)

Abstract

As a part of our ongoing studies of structure–activity relationships regarding cyclohexenyl nucleosides, we were prompted to synthesize a dihydropyranonucleoside as a potential anti-HIV agent. The synthesis of a glycal moiety started from but-2-enediol, which was converted into a di-PMB derivative in several steps. The introduction of an allyl group followed by ring-closing metathesis gave a dihydropyran derivative. After isomerization of the double bond catalyzed by Wilkinson’s catalyst, the resulting glycal, 2,3-bis[(4-methoxybenzyloxy)methyl]-3,4-dihydro-2H-pyran, was subjected to an oxidative glycosylation reaction mediated by hypervalent iodine. Treatment of 2,3-bis[(4-methoxybenzyloxy)methyl]-3,4-dihydro-2H-pyran with (PhSe)2/PhI(OAc)2/TMSOTf (cat.) gave the desired pyranyluracils as a mixture of anomers that were converted into the final target, dihydropyranocytidine, after several manipulations and separation of the anomers.

Supporting Information

 
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