Combinatorial libraries based on a novel and readily accessible “centroid” scaffold

Neustadt, Bernard R.; Smith, Elizabeth M.; Nechuta, Terry; Zhang, Yongzheng

doi:10.1016/s0040-4039(98)01076-4

“…The orthogonally protected centroid aromatic scaffold 1 was synthesized from commercially available 3-amino-5-nitrobenzoic acid via Fmoc protection to give 2, with reduction to 3 [5] and subsequent Boc protection (Scheme 3).…”

Section: Resultsmentioning

confidence: 99%

Microwave-Assisted Synthesis of Aryl Amide Bonds on Solid Phase

Helliwell

¹

,

Fake

²

,

Kerr

³

et al. 2010

Synthetic Communications

2

0

View full text Add to dashboard Cite

“…[6] They also suggested the possibility of continuing peptide elongation from the benzylamino group without protection of the arylamino group. This species was capable of subsequently acylating AlaϪOMe to give the desired dipeptide ester AmAbz(Fmoc)ϪAlaϪOMe 11 in a clean reaction, as shown by HPLC analysis of the reaction medium.…”

Section: Peptide Bond Formation Involving Amabz Derivativesmentioning

confidence: 99%

“…4-Amino-3-(aminomethyl)benzoic acid (1) (AmAbz) [4] fulfils these criteria, but surprisingly, despite its simple structure, its synthesis and reactivity have not yet been investigated. [3,6] Reported syntheses of compounds containing the AmAbz core deal exclusively with N-alkyl derivatives and involve multi-step reactions through nucleophilic substitution on halomethyl aromatic precursors, [7] intramolecular sulfonylamidomethylation of 4-aminobenzoic acid derivatives [8] or FriedelϪCrafts acylation of an o-aminobenzylamine cyclic urea. Pertinent features of AmAbz are: (i) the aromatic cyclic system, which is useful for mimicking a dipeptide residue exhibiting strongly reduced conformational mobility, (ii) two amino groups with a large difference in basicities, allowing the preparation of cyclic or branched peptide analogues, and (iii) a scaffold structure permitting presentation of three independent sets of building blocks, with potential applications in combinatorial chemistry.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of the Novel Amino Acid 4-Amino-3-(aminomethyl)benzoic Acid (AmAbz) and Its Protected Derivatives as Building Blocks for Pseudopeptide Synthesis

Pascal¹,

Sola²,

Labéguère³

et al. 2000

View full text Add to dashboard Cite

4‐Amino‐3‐(aminomethyl)benzoic acid (1) (AmAbz) is a novel unnatural amino acid with promise in applications as a building block for the synthesis of peptidomimetics and as a scaffold for combinatorial chemistry. It was efficiently synthesized in three steps (63% overall yield) from 4‐aminobenzoic acid, by means of regioselective amidomethylation with hydroxymethylphthalimide. AmAbz (1) contains three distinct functionalities which could be discriminated from one another. Firstly, Boc2O or Fmoc−OSu reacted selectively with the benzylamino group to give the monoprotected derivatives AmAbz(Boc) (8a) or AmAbz(Fmoc) (8b), respectively. The absence of acylation at the arylamino group was also noticed in coupling experiments using the BOP reagent and building block 8b. This made protection of the arylamino group unnecessary either for peptide bond formation at the carboxyl group, or for subsequent elongation of a peptide chain at the benzylamino group. Finally, the arylamino group could be acylated under base‐free, carbodiimide‐mediated coupling conditions. These properties are illustrated by the solid‐phase synthesis of the AmAbz‐containing branched pseudopeptide Fmoc−Ala−Phe−AmAbz(H−Lys−Leu)−Val−Gly−NH2 (15). The synthesis of Fmoc−AmAbz(Boc) (10) is also described.

show abstract

“…These results demonstrated that protection of the arylamino group is not necessary for acylation with AmAbz derivatives, which is consistent with results obtained in the related 3,5-diaminobenzoic acid series. [6] They also suggested the possibility of continuing peptide elongation from the benzylamino group without protection of the arylamino group.…”

Section: Peptide Bond Formation Involving Amabz Derivativesmentioning

confidence: 99%

“…Pertinent features of AmAbz are: (i) the aromatic cyclic system, which is useful for mimicking a dipeptide residue exhibiting strongly reduced conformational mobility, (ii) two amino groups with a large difference in basicities, allowing the preparation of cyclic or branched peptide analogues, and (iii) a scaffold structure permitting presentation of three independent sets of building blocks, with potential applications in combinatorial chemistry. [3,6] Reported syntheses of compounds containing the AmAbz core deal exclusively with N-alkyl derivatives and involve multi-step reactions through nucleophilic substitution on halomethyl aromatic precursors, [7] intramolecular sulfonylamidomethylation of 4-aminobenzoic acid derivatives [8] or FriedelϪCrafts acylation of an o-aminobenzylamine cyclic urea. [9] Here we describe a straightforward and efficient noticed in coupling experiments using the BOP reagent and building block 8b.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of the Novel Amino Acid 4-Amino-3-(aminomethyl)benzoic Acid (AmAbz) and Its Protected Derivatives as Building Blocks for Pseudopeptide Synthesis

Pascal¹,

Sola²,

Labéguère³

et al. 2000

Eur. J. Org. Chem.

6

0

View full text Add to dashboard Cite

4‐Amino‐3‐(aminomethyl)benzoic acid (1) (AmAbz) is a novel unnatural amino acid with promise in applications as a building block for the synthesis of peptidomimetics and as a scaffold for combinatorial chemistry. It was efficiently synthesized in three steps (63% overall yield) from 4‐aminobenzoic acid, by means of regioselective amidomethylation with hydroxymethylphthalimide. AmAbz (1) contains three distinct functionalities which could be discriminated from one another. Firstly, Boc2O or Fmoc−OSu reacted selectively with the benzylamino group to give the monoprotected derivatives AmAbz(Boc) (8a) or AmAbz(Fmoc) (8b), respectively. The absence of acylation at the arylamino group was also noticed in coupling experiments using the BOP reagent and building block 8b. This made protection of the arylamino group unnecessary either for peptide bond formation at the carboxyl group, or for subsequent elongation of a peptide chain at the benzylamino group. Finally, the arylamino group could be acylated under base‐free, carbodiimide‐mediated coupling conditions. These properties are illustrated by the solid‐phase synthesis of the AmAbz‐containing branched pseudopeptide Fmoc−Ala−Phe−AmAbz(H−Lys−Leu)−Val−Gly−NH2 (15). The synthesis of Fmoc−AmAbz(Boc) (10) is also described.

show abstract

Combinatorial libraries based on a novel and readily accessible “centroid” scaffold

Cited by 20 publications

References 13 publications

Microwave-Assisted Synthesis of Aryl Amide Bonds on Solid Phase

Microwave-Assisted Synthesis of Aryl Amide Bonds on Solid Phase

Synthesis of the Novel Amino Acid 4-Amino-3-(aminomethyl)benzoic Acid (AmAbz) and Its Protected Derivatives as Building Blocks for Pseudopeptide Synthesis

Synthesis of the Novel Amino Acid 4-Amino-3-(aminomethyl)benzoic Acid (AmAbz) and Its Protected Derivatives as Building Blocks for Pseudopeptide Synthesis

Contact Info

Product

Resources

About