Читать книгу Routes to Essential Medicines - Peter J. Harrington - Страница 54

Anesthetics, Preoperative Medicines and Medical Gases/Preoperative Medication and Sedation for Short‐Term Procedures

Antidotes and Other Substances Used in Poisonings/Specific

Ophthalmological Preparations/Mydriatics

A rigid bicyclic structure is often used to direct the formation of a new chiral carbon.

Discussion. Atropine, a 1 : 1 mixture of the tropane alkaloids (R)‐hyoscyamine and (S)‐hyoscyamine, is usually produced by extraction from the plants Atropa belladonna, Datura stramonium, or Duboisis myoporoides.

Atropine can also be synthesized from tropic acid and tropinone. In the final step of the synthesis, the primary alcohol is released by acetate ester hydrolysis. The tropic acid ester is formed from the acid chloride and the alcohol, 3‐tropanol (tropine).

In a one‐pot procedure, the acetate ester is formed from acetyl chloride and the primary alcohol of tropic acid then the acid chloride is then formed from the carboxylic acid. Tropic acid is formed by hydrolysis of the ethyl ester. The α‐hydroxymethyl ester is formed by reduction of the α‐formyl ester. The α‐formyl ester is formed from ethyl phenylacetate and ethyl formate (mixed Claisen Condensation).

The axial alcohol of tropine is formed by reduction of the ketone. Tropinone is efficiently assembled in a single step from methylamine, 2,5‐dimethoxytetrahydrofuran, and 1,3‐acetonedicarboxylic acid (Robinson–Schopf Reaction). 1,3‐Acetonedicarboxlic acid is formed by oxidative decarboxylation of citric acid. Citric acid is produced by fermentation.