SYNTHESIS OF RESVERATROL-BASED COMPOUNDS

Throughout this application, various publications are referenced by citation in parentheses. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art as known to those skilled therein as of the date of the invention described and claimed herein.

BACKGROUND

The past decade has witnessed tremendous interest in the relatively small natural product resveratrol (1, FIG. 1) based primarily on its possession of a promising and selective array of in vitro and in viva activity against a collection of disease states, including inflammation, heart disease, aging, and cancer [1]. In fact, its truly unique biochemical profile, coupled with its relatively high concentration in red wine (˜100 mM) and near absence in white varietals and grape juice, has led to the popularly held notion that resveratrol is the main protagonist for the so-called “French paradox” [2]. Amazingly, however, virtually no effort has been devoted to the large family of resveratrol-based oligomers (such as 2-8) [3] produced combinatorially by plants throughout the world in response to environmental stress, compounds which initial screening suggest should have unique, if not superior, activity profiles to resveratrol itself [4].

SUMMARY OF THE INVENTION

In one embodiment, this invention provides a compound having the structure

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- wherein
- bond α is present or absent,
  - wherein when bond α is absent, then R₁is ═O or S(CH₂)_1-3-phenyl and
  - when bond α is present, then R₁is H,
    - wherein the phenyl is substituted or unsubstituted;
- R₂, R₃, R₄, R₅, R₆, R₇, R₈, R₉and R₁₀are independently H or OR₁₁
  - wherein each occurrence of R₁₁is independently H, methyl, substituted or
  - unsubstituted alkyl, substituted or unsubstituted aryl, phosphate, sulfate, sulfonic ester, or ester;
- when α is absent and R₁is ═O, then R₁₀is other than OH; and
- when α is absent and R₁is S(CH₂)_1-3-phenyl, then R₁₀is other than OCH₃, or a salt thereof.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1: Selected examples of polyphenolic natural products presumed to arise from the union of resveratrol monomers.

FIG. 2: Synthetic scheme detailing the synthesis of compounds A, C, D, F, G, I, and J.

FIG. 3: Synthetic scheme detailing the synthesis of compounds B, E and H.

DETAILED DESCRIPTION

This invention provides a compound having the structure

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- wherein
- bond α is present or absent,
  - wherein when bond α is absent, then R, is ═O or S(CH₂)_1-3-phenyl and
  - when bond α is present, then R, is H,
    - wherein the phenyl is substituted or unsubstituted;
- R₂, R₃, R₄, R₅, R₆, R₇, R₈, R₉and R₁₀are independently H or OR₁₁
  - wherein each occurrence of R₁₁is independently H, methyl, substituted or
  - unsubstituted alkyl, substituted or unsubstituted heteroalkyl substituted or
  - unsubstituted aryl, substituted or unsubstituted aryl, phosphate, sulfate, sulfonic ester, or ester;
- when α is absent and R₁is ═O, then R₁₀is other than OH; and
- when α is absent and R₁is S(CH₂)_1-3-phenyl, then R₁₀is other than OCH₃,
  
  or a salt thereof.

In some embodiments, the invention includes the compound wherein in the compound each occurrence of R₁₁is independently H, CH₃, C(O)CH₃, P(O)(OR₁₂)₂, SO₂OR₁₂, SO₂R₁₃, or C(O)R₁₃,

- wherein each occurrence of R₁₂is independently H, methyl, substituted or unsubstituted alkyl, or substituted or unsubstituted aryl,
- wherein each occurrence of R₁₃is independently H, methyl, substituted or unsubstituted alkyl, or substituted or unsubstituted aryl,
  
  or a salt thereof.

In some embodiments, the invention includes the compound wherein in the compound

- R₃and R₅are OR₁₁; and R₂and R₄are H,
  
  or a salt thereof.