Solid-phase synthesis of 1,2,3,4-tetrahydroisoquinoline derivatives employing support-bound tyrosine esters in the Pictet-Spengler reaction

Journal of Combinatorial Chemistry
Timothy R KaneJeffrey M Dener

Abstract

The solid-phase synthesis of 1,2,3,4-tetrahydroisoquinoline-3-carboxamides employing carboxyl-supported, o-alkylated tyrosine esters in a Pictet-Spengler reaction is described. Esterification of [4-(hydroxyphenyl)thiomethyl]polystyrene (Marshall resin) with ethers of N-BOC-L-tyrosine using diisopropylcarbodiimide (DIC) and 4-dimethylaminopyridine (4-DMAP) afforded the solid-supported ester derivatives. Removal of the BOC group with trifluoroacetic acid (TFA) afforded the carboxyl-supported tyrosine ester, which was then treated with paraformaldehyde and TFA to afford the desired solid-supported counterpart. Acylation of the secondary amine with arylsulfonyl chlorides followed by reaction with amines resulted in the formation of the desired 2-arylsulfonyl-7-alkoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxamides. Alternatively, the support-bound tetrahydroisoquinoline-3-carboxylate derivatives could be treated with an aldehyde and a reducing agent to give the corresponding support-bound tertiary amine. Exposure of these resin-bound products to amines afforded the corresponding 2-alkyl-7-alkoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxamides after cleavage from the resin. Alternative routes to the desired chemotypes, as well optimizat...Continue Reading

References

Jul 10, 2001·Journal of Combinatorial Chemistry·A M BoldiT P Hopkins
Apr 1, 1997·Chemical Reviews·Adel NefziRichard A. Houghten

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Citations

Jan 26, 2013·Chemical Reviews·Bagher Eftekhari-SisAli Akbari
Oct 27, 2007·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Meglena I KandinskaMariana D Palamareva
Jan 24, 2019·MMW Fortschritte der Medizin·Matthias Keidel, Torsten Kraya
Oct 27, 2010·Organic & Biomolecular Chemistry·Ekaterina ShinkevichKourosch Abbaspour Tehrani

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