Synthesis and Applications of Conformationally Constrained Phenylalanine Analogues

Guillo, Nathalie; Kalindjian, S. Barret; Tozer, Matthew J.; Whitcombe, Nicole J.

doi:10.1007/978-1-4615-4801-0_40

Cited by 3 publications

(3 citation statements)

References 16 publications

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“…The use of conformational restrictions for the development of topographically well-defined peptide analogues with improved potency and/or selectivity is an established approach in peptide-based drug design. Toward this end, 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) has seen increased use as a conformationally constrained phenylalanine analogue in the synthesis of peptide analogues [1][2][3][4][5] with welldefined side-chain orientations. Although the tetrahydroisoquinoline ring system structurally provides several positions for further modification of Tic in order to probe features of the ligand binding site, relatively few Tic derivatives have been reported, largely due to limitations in the standard approach for the synthesis of Tic.…”

Section: Introductionmentioning

confidence: 99%

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Mosberg

1999

Letters in Peptide Science

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A straightforward approach for the synthesis of several new, aryl-substituted derivatives of the conformationally constrained phenylalanine analogue 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) is described. Tic, nitrosubstituted at the 6 or 7 position, was prepared by base-catalyzed cyclization of diethyl acetamidomalonate with α,α-dibromo-4-nitro-o-xylene followed by decarboxylation and deacylation under refluxing conditions in aqueous HCl. Catalytic hydrogenation of nitro-Tic in the presence of 10% Pd/C afforded amino-Tic, which was then converted to iodo-Tic by a modified Sandmeyer reaction. Both amino-Tic and iodo-Tic can easily be transformed to other substituents.

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Section: Introductionmentioning

confidence: 99%

Untitled

Mosberg

1999

Letters in Peptide Science

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“…19,26,27 It has also been used for activation of conjugated carboxylic acids (eq 5) 28. PyBroP also gives good results for the synthesis of macrocyclic lactams (eq 6),29 including cyclic peptides at high dilution 13 with addition of HOAt 30 or on solid phase.…”

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Bromotripyrrolidinophosphonium Hexafluorophosphate

Coste¹,

Jouin²

2002

Encyclopedia of Reagents for Organic Synthesis

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“…7 The products of the Heck reaction (2a-c) were hydrogenated to 3a-c which in turn were deprotected to give the required amino acids. Subsequent incorporation of Tic, Sic, Hic and Nic into a cholecystokinin-B/gastrin receptor antagonist revealed a significant difference in biological activity between the Niccontaining ligand and the other ligands, 8 the source of which is currently being actively pursued.…”

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confidence: 99%