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Structurally homogeneous and heterogeneous synthetic combinatorial libraries

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Summary

We have designed and synthesized structurally homogeneous and heterogeneous nonpeptide libraries. Structurally homogeneous libraries are characterized by the presence of one common structural unit, a scaffold, in all library compounds (e.g. cyclopentane, cyclohexane, diketopiperazine, thiazolidine). In structurally heterogeneous libraries different organic reactions (acylation, etherification, reductive amination, nucleophilic displacement) were applied to connect bifunctional building blocks unrelated in structure (aromatic hydroxy acids, aromatic hydroxy aldehydes, amino alcohols, diamines, and amino acids). The focus of this communication is to document the use of bifunctional building blocks for the design and synthesis of structurally heterogeneous libraries ofN-(alkoxy acyl)amino acids, N,N′-bis-(alkoxy acyl)diamino acids,N-acylamino ethers,N-(alkoxy acyl)amino alcohols,N-alkylamino ethers, andN-(alkoxy aryl)diamines.

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Abbreviations

AcOH:

acetic acid

DCE:

dichloroethane

DCM:

dichloromethane

DEAD:

diethyl azodicarboxylate

DIAD:

diisopropyl azodicarboxylate

DIC:

diisopropyl carbodiimide

DIEA:

diisopropylethylamine

DMAP:

dimethylaminopyridine

DMF:

dimethylformamide

Fmoc:

fluorenylmethyloxycarbonyl

HOBt:

N-hydroxybenzotriazole

MeCN:

acetonitrile

MeOH:

methanol

NaOH:

sodium hydroxide

PEG/PS:

polyethylene-grafted copolystyrene

PPh3 :

triphenylphosphine

t-Bu:

tert- butyl

TFA:

trifluoroacetic acid

TG:

TentaGel

THE:

tetrahydrofuran

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Author notes

  1. Michal Lebl

    Present address: Houghten Pharmaceuticals Inc., 3550 General Atomics Court, 92121, San Diego, CA, USA

Authors and Affiliations

  1. Selectide Corporation, a subsidiary of Hoechst Marion Roussel, 1580 E. Hanley Boulevard, 85737, Tucson, AZ, USA

    Viktor Krchňák, Aleksandra S. Weichsel, Dasha Cabel, Zuzka Flegelova & Michal Lebl

Authors
  1. Viktor Krchňák
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  2. Aleksandra S. Weichsel
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  3. Dasha Cabel
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  4. Zuzka Flegelova
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  5. Michal Lebl
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Krchňák, V., Weichsel, A.S., Cabel, D. et al. Structurally homogeneous and heterogeneous synthetic combinatorial libraries. Mol Divers 1, 149–164 (1996). https://doi.org/10.1007/BF01544953

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