Prostaglandin synthesis in the series 8-aza-10-thia-11-deoxy-PGE

Author(s)

Alessandra Rodrigues Rufino

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ)
• Defense date: 2000-06-16

Examining board members

Francisco Carlos Biaggio; Luiz Carlos Dias; Reinaldo Romero Vargas

• Advisor: Francisco Carlos Biaggio

Abstract

The synthesis of the prostaglandin analog, n-heptyl-4-(3-hydroxy-trans-1-octenyl)-1,3-thiazolidin-2-thione, was carried through the following steps: cyclopentane ring obtainment; N-alkylation of 4-(R)-ethoxycarbonyl-1,3-thiazolidin-2-tione; obtainment of the alcohol from the N-alkyl derivative compound; oxidation of the alcohol to the corresponding aldehyde; introduction of the ω-chain in the : cyclopentane ring of the prostaglandin analog; and finally, the reduction of the enone to the corresponding allyl alcohol. The final product was obtained as a distereomeric mixture. The cystein utilized as starting material; is responsible for the prostaglandin cyclopentane ring formation (the reaction key intermediate). The step of introduction the ω-chain in the cyclopentanone ring, by means of an N-alkylation, it was needed to reduce an intermediate esther, and the formed alcohol was further protected conveniently, thus avoiding possible CxN- and OxN-alkylation competition reactions, respectively. Afther removal of the protecting group from the alcohol, it was oxidized to the corresponding aldehyde employing different oxidizing agents. Among these, the Swern reagent was chosen for the work, because of its greater selectivity. The introduction of the ω-chain into the five membered ring of the prostaglandin analog was performed via a Horner-Wadsworth-Emmons reactions, using a stabilized phosphorane in order to guarantee the E configuration of the double bond formed on C13 - C14, commonly found in natural prostaglandins. The prostaglandins obtained in this way will have its possible biological activities assayed as bronchodilatory or platelet aggregations inhibition agent in the Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBIO). (AU)