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. 2024 Oct 11;26(40):8527-8531.
doi: 10.1021/acs.orglett.4c03105. Epub 2024 Sep 27.

Synthesis of Monodehydro-Diketopiperazines Enabled by Cp*Rh(III)-Catalyzed Amine-Directed N-H Functionalization

Jenna C Molas  1 , Emily M Poag  1 , Jonathan A Ellman  1
Affiliations

Synthesis of Monodehydro-Diketopiperazines Enabled by Cp*Rh(III)-Catalyzed Amine-Directed N-H Functionalization

Jenna C Molas et al. Org Lett. .

Abstract

A two-step, diversity-building sequence to prepare monodehydro-diketopiperazines from readily accessible materials is reported. Rh(III)-catalyzed, amine-directed N-H functionalization of a variety of α-amino amides with a diazophosphonate ester and subsequent cyclization gives phosphonate-substituted diketopiperazines. A Horner-Wadsworth-Emmons reaction then provides monodehydro-diketopiperazines with high E-alkene selectivity. This transformation was used to incorporate a variety of groups originating from diverse aldehydes and ketones with different steric and electronic properties. Face-selective hydrogenation to diketopiperazines is also disclosed.

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Conflict of interest statement

The authors declare no competing financial interest.

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References

    1. Borthwick AD 2,5-Diketopiperazines: Synthesis, Reactions, Medicinal Chemistry, and Bioactive Natural Products. Chem. Rev. 2012, 112, 3641–3716. - PubMed
    1. Zhao K; Xing R; Yan X Cyclic dipeptides: Biological activities and self-assembled materials. Peptide Sci. 2021, 113, No. e24202.
    2. Goher SS; Abdrabo WS; Veerakanellore GB; Elgendy B 2,5-Diketopiperazines (DKPs): Promising Scaffolds for Anticancer Agents. Curr. Pharm. Design 2024, 30, 597–623. - PubMed
    1. Yee DA; Niwa K; Perlatti B; Chen M; Li Y; Tang Y Genome mining for unknown–unknown natural products. Nat. Chem. Biol. 2023, 19, 633–640. - PMC - PubMed
    1. Hayashi Y; Yamazaki-Nakamura Y; Yakushiji F Medicinal Chemistry and Chemical Biology of Diketopiperazine-Type Anti-microtubule and Vascular-Disrupting Agents. Chem. Pharm. Bull. 2013, 61, 889–901. - PubMed
    2. Liao S-R; Qin X-C; Wang Z; Li D; Xu L; Li J-S; Tu Z-C; Liu Y Design, synthesis and cytotoxic activities of novel 2,5-diketopiperazine derivatives. Eur. J. Med. Chem. 2016, 121, 500–509. - PubMed
    3. Kim MC; Cullum R; Machado H; Smith AJ; Yang I; Rodvold JJ; Fenical W Photopiperazines A–D, Photosensitive Interconverting Diketopiperazines with Significant and Selective Activity against U87 Glioblastoma Cells, from a Rare, Marine-Derived Actinomycete of the Family Streptomycetaceae. J. Nat. Prod. 2019, 82, 2262–2267. - PubMed
    4. Ding Z; Li F; Xie L; Gu M; Li C; Liu C; Peng C; Li W Design and Synthesis of Novel Phenylahistin Derivatives Based on Co-Crystal Structures as Potent Microtubule Inhibitors for Anti-Cancer Therapy. Mar. Drugs 2022, 20, 752. - PMC - PubMed
    1. Liebscher J; Jin S 3-Ylidenepiperazine-2,5-diones as versatile organic substrates. Chem. Soc. Rev. 1999, 28, 251–259.

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