(S)-(−)-α-Methylbenzylamine as an efficient chiral auxiliary in enantiodivergent synthesis of both enantiomers of N-acetylcalycotomine

Variety of natural products derived from tryptophan and stereoselective synthesis of tetrahydro-β-carboline derivatives of pharmacological importance

“…In contrast to previous results in the isoquinoline series [19], the increase of steric parameters, neither in the reducing agent molecule nor in the imine-containing target derivative 8, gave a significant improvement of the stereochemical outcome. In a search for a feasible explanation of the above observation we investigated the problem using quantum chemical methods.…”

“…The Bischler-Napieralski cyclization followed by a diastereoselective reduction of the imine bond were the key steps in enantiodivergent synthesis of both enantiomers of N-acetylcalycotomine that were carried out in our laboratory [19].…”

“…The configuration at C-1 in both compounds was assigned indirectly based on the comparison of the 1 H and 13 C NMR spectroscopic data and the specific rotation values with those recorded for the isoquinoline series prepared previously by us [19] and for which the stereochemistry was established by Xray studies. Seeking further improvement in stereoselectivity, we decided to apply the same synthetic sequence using (R)-(+)-1-(-1-naphthyl)ethylamine 4 as a chiral auxiliary, another well-known and effective chiral inductor [17].…”

“…A strong hydrogen bond between the amide carbonyl group and the indole NH define the basic shape of the reacting part of the molecule causing the chiral auxiliary part to adopt a remote position from the imine moiety. Apparently, such a disfavoring interaction was not present in the isoquinoline analog of imine 7, allowing us to achieve much better chirality induction [19].…”

Synthesis of Bioactive 2‐Aza‐Analogues of Ipecac and Alangium Alkaloids

“…For the preparation of 14, the Fmoc-protected tetrahydroisoquinoline-1-carboxylic acid rac-16 obtained in five steps from homoveratrylamine was used as the coupling component for the northern half of the compound. [20][21][22] Acylation of amine 11 was achieved according to a modified Steglich protocol. [23] After removal of the Fmoc group, double reduction yielded 14 with high diastereoselectivity.…”