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. 2023 Jul 21;88(14):9910-9919.
doi: 10.1021/acs.joc.3c00673. Epub 2023 Jul 10.

Conversion of Hydroxyproline "Doubly Customizable Units" to Hexahydropyrimidines: Access to Conformationally Constrained Peptides

Dácil Hernández  1 , Marina Porras  1 , Alicia Boto  1
Affiliations

Conversion of Hydroxyproline "Doubly Customizable Units" to Hexahydropyrimidines: Access to Conformationally Constrained Peptides

Dácil Hernández et al. J Org Chem. .

Abstract

The efficient transformation of hydroxyproline "doubly customizable units" into rigid hexahydropyrimidine units takes place in good global yields and generates compounds of pharmaceutical interest. In particular, the process can readily provide access to peptidomimetics and peptides with reversed sequences or with valuable turns.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Previous Results and Current Work on Doubly Customizable Units
Scheme 2
Scheme 2. Use of In Situ-Formed Hexahydropyrimidines for Modulation of the Peptide Structure
Scheme 3
Scheme 3. Oxidative Radical Scission of Substrates 2a–2d to Give Pure Enantiomers 5a–5d
Scheme 4
Scheme 4. Reductive Amination of Scission Products 5a–5c
Scheme 5
Scheme 5. Synthesis of Hexahydropyrimidines with Different Reversed Sequences
Scheme 6
Scheme 6. Synthesis of Hexahydropyrimidines in Peptides
Figure 1
Figure 1
3D representation of the minimized conformation for compound 18, showing reversed sequences.
Scheme 7
Scheme 7. Turn-Inducing Hexahydropyrimidine 26
Figure 2
Figure 2
3D representation of the minimized conformation for compound 26 with NOESY correlations shown by arrows (strong interactions in orange and weak interactions in green). The rigid bicyclic unit is formed during peptide ligation and forces the peptide backbone to form a turn as shown.
See this image and copyright information in PMC

References

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