Cyanoamidine Cyclization Approach to Remdesivir's Nucleobase.

Knapp, Rachel R; Tona, Veronica; Okada, Taku; Sarpong, Richmond; Garg, Neil K

Knapp, Rachel R; Tona, Veronica; Okada, Taku; Sarpong, Richmond; Garg, Neil K.

Knapp RR; Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095-1569, United States.
Tona V; Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095-1569, United States.
Okada T; Department of Chemistry, University of California, Berkeley, California 94720, United States.
Sarpong R; Department of Chemistry, University of California, Berkeley, California 94720, United States.
Garg NK; Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095-1569, United States.

Org Lett ; 22(21): 8430-8435, 2020 11 06.

Article in English | MEDLINE | ID: covidwho-882861

ABSTRACT

ABSTRACT

We report an alternative approach to the unnatural nucleobase fragment seen in remdesivir (Veklury). Remdesivir displays broad-spectrum antiviral activity and is currently being evaluated in Phase III clinical trials to treat patients with COVID-19. Our route relies on the formation of a cyanoamidine intermediate, which undergoes Lewis acid-mediated cyclization to yield the desired nucleobase. The approach is strategically distinct from prior routes and could further enable the synthesis of remdesivir and other small-molecule therapeutics.

Subject(s)

Adenosine Monophosphate/analogs & derivatives; Alanine/analogs & derivatives; Amidines/chemistry; Antiviral Agents/chemistry; Antiviral Agents/chemical synthesis; Adenosine Monophosphate/chemical synthesis; Adenosine Monophosphate/chemistry; Adenosine Monophosphate/therapeutic use; Alanine/chemical synthesis; Alanine/chemistry; Alanine/therapeutic use; Antiviral Agents/therapeutic use; COVID-19; Chemistry Techniques, Synthetic; Coronavirus Infections/drug therapy; Cyclization; Pandemics; Pneumonia, Viral/drug therapy

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Adenosine Monophosphate / Alanine / Amidines Type of study: Experimental Studies / Prognostic study Language: English Journal: Org Lett Journal subject: Biochemistry Year: 2020 Document Type: Article Affiliation country: Acs.orglett.0c03052

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