Synthesis of 2-methoxy and 4-methoxy equine estrogens.

The researchers have developed a process to synthetically produce 2-methoxy and 4-methoxy equine estrogens, types of hormones found in horses.

Synthesis process of 2-methoxy and 4-methoxy equine estrogens

The authors presented a well-defined methodology of synthesizing 4-methoxyequilin and 2-methoxyequilin, all done through altering the chemical composition of related compounds.

• 4-methoxyequilin and 2-methoxyequilin were initially synthesized from 4-bromoequilin and 2-iodoequilin derivatives respectively.
• The process of synthesis included a nucleophilic displacement reaction in which the halogen (bromine in 4-bromoequilin and iodine in 2-iodoequilin) was replaced with a methoxide ion. This was facilitated by copper (II) chloride and 15-crown-5-ether which acted as catalysts.
• 4-bromoequilin was made by reacting equilin with one equivalent of N-bromoacetamide.
• 2-iodoequilin was made differently. It was synthesized from 2,4-diiodoequilin, which was then further synthesized by treating equilin with two equivalents of iodine in a methanolic ammonium hydroxide solution.

Synthesis of 4-methoxy-equilenin and 2-methoxyequilenin

The study also elucidated the process for the synthesis of 2-methoxyequilenin and 4-methoxy-equilenin from the corresponding 4-iodo- and 2-iodo-7 epsilon, 8 epsilon-epoxyestrone derivatives.

• Nucleophilic displacement of iodine with methoxide ion was carried out like before, which also lead to aromatization of the B ring forming the 4- and 2-methoxyequilenin derivatives.
• There was an alternative approach to synthesize 4-methoxyequilenin from 4-methoxyequilin using selenium dioxide oxidation.

In summary, the research demonstrates a novel and detailed protocol for the synthesis of 2-methoxy and 4-methoxy equine estrogens using several chemical reactions, various catalysts, and different starting compounds.