Synthesis of tadalafil (Cialis) from l-tryptophan

Peptides and peptidoaldehydes as substrates for the Pictet–Spengler reaction

“…During the reaction, the new, six-membered ring is formed, and a stereogenic center is generated [3][4][5]. The reaction is useful in the field of heterocycles, but also constrained analogs of aromatic amino acids may be prepared [6][7][8][9][10][11][12]. Such compounds exhibit biological activity [13] or, after incorporation into the peptide chains, may change the pharmacological properties of the parent peptides and provide insight into their bioactive conformation [14][15][16].…”

An Efficient and General Method for the Stereodivergent Syntheses of Tadalafil‐Like Tetracyclic Compounds

“…It is worthy to note that the base-catalyzed epimerization at C-3 position of 1,2,3-trisubstituted-tetrahydro-β-carbolines was reversible and gave a mixture of epimers in equilibrium, [8] but here the epimerization of compounds 2a-2t was complete and gave compounds 3a-3t in almost quantitative yields. Moreover, when compounds 3a, 3b, 3j, 3m and 3r were treated with weak or strong bases in a mixture of solvents (DMSO and ethanol, 1:5) under different conditions (Table 2, Entries 1-8), no reversed epimerization was observed at all.…”

First highly stereocontrolled synthesis of tetrahydro trans-β-carboline derivatives by exploiting the influence of a cyclic amide

“…Pictet-Spengler reaction were found to utilize amines, substituted amines 1,3,12,14,15,22 or carbamates 23 for β-carboline synthesis. However, in our approach, we utilized amide 15 to yield β-carboline derivatives 17a-c and 12 as shown in Scheme 4.…”

“…13 Unlike to amino ester, β-carboline trans-4, isomerization of trans-tadalafil 12 to tadalafil 1c was unsuccessfully attempted (Figure 2). An alternative synthesis of 1c was reported 14 starting from L-tryptophan in seven steps.…”