Issue 90, 2015

Stereoselective synthesis of functionalized 1,2,3,4-tetrahydroisoquinolines (THIQs) via highly diastereoselective Ugi three-component reactions (U3CRs) with chiral 3,4-dihydroisoquinolines (DHIQs)

Abstract

A highly diastereoselective Ugi three-component reaction (U3CR) involving chiral 3,4-dihydroisoquinolines (DHIQs), isocyanides and carboxylic acids has been developed to synthesize enantiopure 1,2,3,4-tetrahydroisoquinolines (THIQs). The inherent chirality of DHIQ at C-3 and C-4 controls the addition of isocyanide at C-1 to induce excellent diastereoselectivity. The method was applied to a variety of aromatic and aliphatic acids, and in most cases the reaction proceeded smoothly without formation of any side products. The experimental and computational studies demonstrated the role of internal chirality in the conformational stability of the intermediate in order to control the facial selectivity and strong solvent effect on the reaction. Cytotoxicity of selected compounds was also evaluated against four types of human cancer cell lines, MCF-7 (breast cancer), MDA MB-231 (breast cancer), DU-145 (prostate cancer), A549 (lung cancer) and HepG2 (liver cancer), where few compounds exhibited GI50 values in the submicromolar range.

Graphical abstract: Stereoselective synthesis of functionalized 1,2,3,4-tetrahydroisoquinolines (THIQs) via highly diastereoselective Ugi three-component reactions (U3CRs) with chiral 3,4-dihydroisoquinolines (DHIQs)

Supplementary files

Article information

Article type
Paper
Submitted
11 Jun 2015
Accepted
19 Aug 2015
First published
20 Aug 2015

RSC Adv., 2015,5, 73373-73380

Author version available

Stereoselective synthesis of functionalized 1,2,3,4-tetrahydroisoquinolines (THIQs) via highly diastereoselective Ugi three-component reactions (U3CRs) with chiral 3,4-dihydroisoquinolines (DHIQs)

T. Ramanivas, G. Gayatri, D. Priyanka, V. L. Nayak, K. K. Singarapu and A. K. Srivastava, RSC Adv., 2015, 5, 73373 DOI: 10.1039/C5RA11144G

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