Synthesis of tadalafil (Cialis) from l-tryptophan |
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Authors: | Sen Xiao Xiao-Xin Shi Jing Xing Jing-Jing Yan Shi-Ling Liu Wei-Dong Lu |
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Institution: | aDepartment of Pharmaceutical Engineering, School of Pharmacy, East China University of Science and Technology, PO Box 363, 130 Mei-Long Road, Shanghai 200237, PR China |
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Abstract: | The first synthesis of tadalafil 1 (Cialis) from l-tryptophan is described. The title compound 1 was synthesized via seven steps from l-tryptophan methyl ester hydrochloride in 42.3% overall yield. Two characteristic steps involved in this synthesis are the base-catalyzed epimerization of the C-3 position of (1S,3S)-1,2,3-trisubstituted-tetrahydro-β-carboline 3a and the acid-catalyzed epimerization of the C-1 position of (1S,3R)-1,3-disubstituted-tetrahydro-β-carboline 5. The (S)-configurations at C-1 and C-3 were inverted to (R)-configurations during the epimerization reactions. The base-catalyzed epimerization of C-3 of (1S,3S)-1,2,3-trisubstituted-tetrahydro-β-carbolines 3a–3e was also studied in detail. |
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