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Synlett 2010(15): 2275-2278  
DOI: 10.1055/s-0030-1258529
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

First Total Synthesis of (±)-6′-Methoxyretrojusticidin B Using Regiocontrolled Benzannulation: Structural Inconsistency with Procumphthalide A and Its Revision to 5′-Methoxyretrochinensin

Eri Yoshidaa, Daisuke Yamashitaa, Ryo Sakaia, Yoo Tanabeb, Yoshinori Nishii*a
a Department of Chemistry, Faculty of Textile Science and Technology, Shinshu University, Ueda, Nagano 386-8567, Japan
Fax: +81(268)215391; e-Mail: nishii@shinshu-u.ac.jp;
b Department of Chemistry, School of Science and Technology, Kwansei Gakuin University, Sanda, Hyogo 669-1337, Japan
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Publication History

Received 1 June 2010
Publication Date:
30 July 2010 (online)

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Abstract

We achieved the first total synthesis of a novel (±)-6′-methoxyretrojusticidin B, which was proposed as procumphthalide A, utilizing regiocontrolled benzannulation of an aryl(aryl′)-2,2-dichlorocyclopropylmethanol as the key step. ¹H NMR spectral data suggested that the structure of the synthesized product, 6′-methoxy­retrojusticidin B, was inconsistent with that of natural procumphthalide A. A computational study of the rotational barrier rationally supports the existence of a rigid chiral axis in 6′-methoxyretrojusticidin B. The revised structural elucidation of natural procumphthalide A was concluded to be 5′-methoxyretrochinensin.

Key words

total synthesis - natural product - annulation - lignan lactone - revised structure

    References and Notes

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The addition proceeded with high syn-diastereoselectivity (>95:5) according to the reported method:6b ArLi attacked the less hindered side of the preferential s-cis conformer of ketone 2a or 2b following the Cram’s rule.

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AACM 3a was completely consumed but inseparable complex byproducts were yielded.

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Tetrabrominated product 5 was obtained as inseparable regioisomers, and the structure was difficult to be determined due to a complex ¹H NMR spectrum.

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Undesirable counter regioisomer was yielded in ca. 10%. The regioselectivity favors the synthesis of retrotype lignan lactones.

17

Data in ref. 6b. ¹H NMR (400 MHz, CDCl3): δ = 3.87 (2 × 3 H, s), 3.96 (3 H, s), 5.22 (2 H, s), 6.10 (2 H, s), 6.54 (2 × 1 H, s), 7.11 (1 H, s), 7.31 (1 H, s), 8.27 (1 H, s).