Expedient synthesis and design strategies for new peptoid construction

Organic Letters

Volumn 7, Issue 8, 2005, Pages 1521-1524

  Gorske, Benjamin C ^a   Jewell, Sarah A ^a   Guerard, Emily J ^a   Blackwell, Helen E ^a  

^a UNIVERSITY OF WISCONSIN MADISON   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINE; OLIGOMER; PEPTOID;

ARTICLE; CHEMICAL STRUCTURE; MICROWAVE RADIATION; MOLECULAR STABILITY; PEPTIDE SYNTHESIS; SOLID PHASE SYNTHESIS; STRUCTURE ANALYSIS;

COMBINATORIAL CHEMISTRY TECHNIQUES; MICROWAVES; MOLECULAR STRUCTURE; PEPTOIDS;

EID: 17844376473     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol0502984     Document Type: Article

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18. Commercial MW reactors allow for real-time temperature monitoring and variable power control during chemical reactions.
19. All MW-assisted reactions were performed in a Milestone Ethos Microsynth multimodal microwave reactor.
20. See the Supporting Information for full details of room-temperature and MW-assisted synthesis, characterization, and purification methods.
21. The major impurities observed in peptoid syntheses were either terminal bromides or oligomers with one or more monomer deletions (as determined by LC-MS analyses).
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23. A report of our syntheses of (±)-1-(pentafluorophenyl)ethylamine (fpe, 9) and (S)-1-(pentafluorophenyl)ethylamine is forthcoming.
24. 5 peptoids in order to conserve this valuable amine. We found that 10 couplings could be performed by recycling the same 2 mL of 1 M amine solution before product purity was affected (by >5%).
25. Aniline was incorporated into peptoids more efficiently using the MW method relative to the 25°C control, albeit with reduced purities overall (30% vs 11% for a homopentamer); see the Supporting Information.
26. The heating profile of a compound under MW irradiation is directly dependent on its dielectric constant. See ref 11a,c.
27. These control studies are complicated by our inability to attain the rapid heating profile achieved in the MW reactor for the amination step (25-95°C in 90 s) using conventional heating methods (e.g., in an oil or sand bath).
28. 9 22 was synthesized using the MW-assisted method described herein. Peptoids were purified to ≥95% homogeneity by reverse-phase HPLC prior to CD analysis. (24) Peptoid 21 could also experience electrostatically destabilizing side-chain interactions in a helical conformation (Figure 2b).