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Resolving Inflammation: Synthesis, Configurational Assignment, and Biological Evaluations of RvD1n-3?DPA.

ABSTRACT: New drugs that can resolve inflammation without immunosuppressive effects are at the medicinal chemistry frontier. Pro-resolving endogenously formed small molecules, that is, the resolvins, are excellent candidates displaying such bioactions. The first total synthesis of the specialized pro-resolving mediator RvD1n-3?DPA has been achieved using the underutilized sp3 -sp3 Negishi cross coupling reaction and an alkyne hydrosilylation-protodesilylation protocol. Biological evaluations revealed that this novel mediator displays low nanomolar pro-resolving properties and potently activates the human DRV1/GPR32 receptor. As such, this endogenous natural product is a lead compound for the development of novel immunoresolvents.

SUBMITTER: Tungen JE

PROVIDER: S-EPMC6368681 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Resolving Inflammation: Synthesis, Configurational Assignment, and Biological Evaluations of RvD1n-3 DPA.

Tungen Jørn Eivind JE Gerstmann Lisa L Vik Anders A De Matteis Roberta R Colas Romain Alexandre RA Dalli Jesmond J Chiang Nan N Serhan Charles Nicholas CN Kalesse Markus M Hansen Trond Vidar TV

Chemistry (Weinheim an der Bergstrasse, Germany) 20181220 6

New drugs that can resolve inflammation without immunosuppressive effects are at the medicinal chemistry frontier. Pro-resolving endogenously formed small molecules, that is, the resolvins, are excellent candidates displaying such bioactions. The first total synthesis of the specialized pro-resolving mediator RvD1n-3 DPA has been achieved using the underutilized sp3 -sp3 Negishi cross coupling reaction and an alkyne hydrosilylation-protodesilylation protocol. Bio ...[more]

PMID: 30511787

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