title: Total Synthesis of Prostaglandin 15d-PGJ(2) and Investigation of its Effect on the Secretion of IL-6 and IL-12.
abstract: An efficient synthesis of 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2, 1) is reported. The route described allows for diversification of the parent structure to prepare seven analogues of 1 in which the positioning of electrophilic sites is varied. These analogues were tested in SAR studies for their ability to reduce the secretion of proinflammatory cytokines. It was shown that the endocyclic enone is crucial for the bioactivity investigated and that the conjugated ω-side chain serves in a reinforcing manner.
authors: Laboratory of Organic Chemistry, ETH Zurich , HCI H335, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland.
authors: Julian
authors: J
authors: Egger
authors: Laboratory of Organic Chemistry, ETH Zurich , HCI H335, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland.
authors: Stefan
authors: S
authors: Fischer
authors: Institute for Integrative Biology, ETH Zurich , HPL-G 12, Schafmattstrasse 27, 8093 Zurich, Switzerland.
authors: Peter
authors: P
authors: Bretscher
authors: Institute for Integrative Biology, ETH Zurich , HPL-G 12, Schafmattstrasse 27, 8093 Zurich, Switzerland.
authors: Stefan
authors: S
authors: Freigang
authors: Institute for Integrative Biology, ETH Zurich , HPL-G 12, Schafmattstrasse 27, 8093 Zurich, Switzerland.
authors: Manfred
authors: M
authors: Kopf
authors: Laboratory of Organic Chemistry, ETH Zurich , HCI H335, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland.
authors: Erick M
authors: EM
authors: Carreira
mesh_terms: D003517:Cyclopentanes / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D015394:Molecular Structure; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: C477819:15-deoxyprostaglandin J2; D003517:Cyclopentanes; D016207:Cytokines; D015850:Interleukin-6; D018664:Interleukin-12; C013905:cyclopentenone; D015230:Prostaglandin D2