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. 2023 Oct 27;28(21):7303.
doi: 10.3390/molecules28217303.

A New Stereoselective Approach to the Substitution of Allyl Hydroxy Group in para-Mentha-1,2-diol in the Search for New Antiparkinsonian Agents

Alexandra V Podturkina  1 , Oleg V Ardashov  1 , Konstantin P Volcho  1 , Nariman F Salakhutdinov  1
Affiliations

A New Stereoselective Approach to the Substitution of Allyl Hydroxy Group in para-Mentha-1,2-diol in the Search for New Antiparkinsonian Agents

Alexandra V Podturkina et al. Molecules. .

Abstract

Two approaches to the synthesis of para-menthene epoxide ((1S,5S,6R)-4) are developed. The first approach includes a reaction between chlorohydrin 7 and NaH in THF. The second involves the formation of epoxide in the reaction of corresponding diacetate 6 with sodium tert-butoxide. One possible mechanism of this reaction is proposed to explain unexpected outcomes in the regio- and stereospecificity of epoxide (1S,5S,6R)-4 formation. The epoxide ring in (1S,5S,6R)-4 is then opened by various S- and O-nucleophiles. This series of reactions allows for the stereoselective synthesis of diverse derivatives of the monoterpenoid Prottremine 1, a compound known for its antiparkinsonian activity, including promising antiparkinsonian properties.

Keywords: Prottremine; epoxide; monoterpene; nucleophilic substitution; synthetic methods.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Synthesis of Prottremine (1).
Figure 2
Figure 2
Prottremine derivatives.
Figure 3
Figure 3
Synthesis of PA96.
Figure 4
Figure 4
Synthesis of epoxide (1S,5S,6R)-4 from chlorohydrin 7 [34].
Figure 5
Figure 5
Synthesis of epoxide (1S,5S,6R)-4 from diacetate 6.
Figure 6
Figure 6
Synthesis of diacetate 6 stereoisomers.
Figure 7
Figure 7
Reaction between diacetate 6 and t-BuONa at room temperature.
Figure 8
Figure 8
Reaction between diacetate 8 and 9 t-BuONa.
Figure 9
Figure 9
Proposed mechanism for the reaction between diacetate 6 and t-BuONa.
Figure 10
Figure 10
Reaction with diacetate epoxydiol 12 and t-BuONa.
Figure 11
Figure 11
Synthesis of Prottremine derivatives with O-substituents.
Figure 12
Figure 12
Synthesis of Prottremine derivatives with perillyl alcohol and myrtenol.
Figure 13
Figure 13
Synthesis of Prottremine derivatives with S-substituents.
Figure 14
Figure 14
Synthesis of Prottremine derivative with SH group.
See this image and copyright information in PMC

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