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Synthesis 2012(6): 909-919  
DOI: 10.1055/s-0031-1289730
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

A Versatile Intermediate for the Systematic Synthesis of All Regioisomers of myo-Inositol Phosphates

Takashi Masudaa, Kensaku Anrakub, Mitsuhiro Kimuraa, Kaori Satoa, Yoshinari Okamotoa, Masami Otsuka*a
a Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan
Fax: +81(96)3714620; e-Mail: motsuka@gpo.kumamoto-u.ac.jp;
b Institute of Health Sciences, Kumamoto Health Science University, 325 Izumi-machi, Kumamoto 861-5598, Japan
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Publikationsverlauf

Received 9 January 2012
Publikationsdatum:
01. März 2012 (online)

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Abstract

Inositol phosphate derivatives are usually synthesized by repeated protection-deprotection procedures, necessitating development of an independent synthetic route for each inositol derivative. Herein, a synthetic precursor for all regioisomers of inositol phosphate is reported. A cycloadduct obtained by the Diels-Alder reaction of trans-1-methoxy-3-trimethylsilyloxybuta-1,3-diene and methyl vinyl ketone was converted into an inositol derivative by sequential introduction and immediate protection of hydroxy groups. Thus, the six hydroxy groups of the obtained inositol derivative are differentiated by different protective groups that are cleavable under independent conditions. This would enable us to prepare all regioisomers of inositol phosphate derivative.

Key words

inositol phosphate - Diels-Alder reaction - oxidative rearrangement - asymmetric dihydroxylation - monoacylation

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The stereochemistry of 3a and 3b was assigned by comparing with the closely related known compound whose stereochemistry has already been established by Danishefsky.8

11

The relative stereochemistry of 4a and 4b was assigned based on the NMR coupling constants.

13

The relative stereochemistry of 5a and 5b was assigned based on the NMR coupling constants.

18

The stereochemical assignment of 15a and 15b was based on the NMR coupling constants.

20

Stereochemical assignment of 17a was tentative at this stage. The stereochemistry of compound 19 was established at a later step.