20688-07-7

Upstream product

• 96307-21-0 3-cyano-2,5-dihydrothiophene-4-carboxylic acid methyl ester 
• 7647-01-0 hydrogenchloride 
• 64-19-7 acetic acid 
• 155251-30-2 3-cyano-3-hydroxy-tetrahydrothiophene-4-carboxylic acid methyl ester 
• 170945-21-8 methyl 4-{[(trifluoromethyl)sulfonyl]oxy}-2,5-dihydrothiophene-3-carboxylate 
• 7400-45-5 dimethyl-3-thiaadipate 
• 2689-68-1 methyl 4-oxotetrahydrothiophene-3-carboxylate 
• 20946-32-1 3,4-dimethyl 2,5-dihydrothiophene-3,4-dicarboxylate 

Downstream Products

• 75532-25-1 2,2,4,4-tetrahydrothiophene-3,4-dicarboxylic acid anhydride 
• 20946-32-1 3,4-dimethyl 2,5-dihydrothiophene-3,4-dicarboxylate 
• 56-25-7 cantharidin 
• 6626-68-2 2,6-diphenyl-pyrrolo[3,4-f]isoindole-1,3,5,7-tetraone 
• 945561-49-9 2,6-diphenyl-3a,4,8,8a-tetrahydro-pyrrolo[3,4-f]isoindole-1,3,5,7-tetraone 
• 945561-48-8 2,2-dioxo-5-phenyl-2,3-dihydro-1H-2λ⁶-thieno[3,4-c]pyrrole-4,6-dione 
• 945561-47-7 5-phenyl-1,3-dihydro-thieno[3,4-c]pyrrole-4,6-dione 

Relevant academic research and scientific papers

SYNTHESIS OF CANTHARIDIN

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).

The novel method to synthesis of cantharidin intermediate

Sulfur-containing dehydrocantharidin(SD) was yielded (76% to 96%) by Diels-Alder reaction in an ionic-liquid system under ordinary pressure and temperature. We explored the influences of different ionic-liquid types, reaction temperatures, and reaction times in this reaction. We found that the optimal reaction temperature was about 35°C, the reaction time was 20 h, and the most suitable ionic liquid was 1-butyl-3-methylimidazolium tetrafluoroborate. Furthermore, in the recycling process of ionic liquid, we found that CH3CN was the most suitable extraction solvent. We explored four steps in the synthetic route to SD and achieved a good yield of 38% in total. We envisage that this process could be further developed at an industrial scale for the synthesis of Cantharidin and is destined to be an environmentally friendly way to solve the lack of cantharis as a natural resource.

Novel green and environment-friendly synthetic process for cantharidin

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.

COMMERCIALLY VIABLE SYNTHESIS OF CANTHARIDIN AND BIOACTIVE CANTHARIDIN DERIVATIVES

The present disclosure provides methods for synthesizing cantharidin and cantharidin derivatives.

Cycloaddition approach to the curing of polyimides via precursor containing thiophene-S,S-dioxide

A new method for linear polymerization of maleimides via the Diels-Alder reaction has been developed. This method involves use of a new cross-linking agent, benzene-3,4-dimethylenesuccinimide, which can be generated in situ from its thiophene precursor, benzene-2,5-dihydrothiophene-3,4dicarboximide-S,S- dioxide. This new cross-linking agent is reasonably reactive, readily prepared, and stable at room temperature. A controlled molecular weight oligomer has been synthesized and applied to the polymerization to yield a highly thermal stable polyimide.