- SYNTHESIS OF CANTHARIDIN
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The invention provides synthetic methods for the preparation of cantharidin and analogs thereof. In one aspect, the invention provides an improved Diels-Alder cycloaddition to generate a key intermediate en route to cantharidin and analogs thereof. In certain embodiments, the new Diels-Alder reaction involves reacting Compound (2) in the presence of furan, and in the absence of acid or increased pressure, in an aprotic polar solvent with slight warming, to yield Compound (1) in favorable yield and exo-endo ratio. In another aspect, the invention also provides a new Diels-Alder reaction between compounds of Formula (III) and furan to yield compounds of Formula (IV), which can then be transformed into cantharidin or analogs thereof. In yet another aspect, the invention describes a new palladium-mediated carbonylation providing another key intermediate en route to cantharidin and analogs thereof. In addition to synthetic methods, present invention also provides compounds {i.e., intermediates) useful in the synthesis of cantharidin and analogs thereof. Compounds provided herein may have biological activity, and therefore may be used in the treatment of diseases or conditions {e.g., infectious diseases and skin conditions).
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- Novel green and environment-friendly synthetic process for cantharidin
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The invention relates to a novel green and environment-friendly synthetic process for preparing cantharidin under the condition of normal pressure and belongs to the field of synthesis and preparation of medicines. The process comprises the following steps: preparing 3-cyano-3-hydroxy-4-methyl formate-2,5-tetrahydrothiophene from a NaCN aqueous solution; adding benzene, pyridine and POCl3 into thiophene to prepare 3-cyano-4-methyl formate-2,5-dihydrothiophene; then adding acetic acid and concentrated hydrochloric acid, and carrying out reflux reaction to obtain 2,5-dihydrothiophene-3,4-dicarboxylic acid powder; carrying out stirring and refluxing on the prepared dicarboxylic acid and thionyl chloride to prepare 2,5-dihydrothiophene-3,4-dicarboxylic anhydride; carrying out heating reaction according to the solid-liquid ratio of dicarboxylic anhydride to furfuran to ionic liquid being 1mg:(3.5 to 6[mu]l):(2 to 4[mu]l), extracting and carrying out Raney-Ni reflux to obtain the cantharidin. According to the process, superhigh pressure condition and equipment are not needed, and overnight reaction at the temperature of 20 to 50DEG C is carried out; the process has the advantages of mild conditions, high conversion rate, and high yield of the cantharidin, and provides favorable conditions for industrial production of the cantharidin.
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- COMMERCIALLY VIABLE SYNTHESIS OF CANTHARIDIN AND BIOACTIVE CANTHARIDIN DERIVATIVES
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The present disclosure provides methods for synthesizing cantharidin and cantharidin derivatives.
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Paragraph 0111
(2016/07/05)
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