Synthesis of 5-monobromocavernicolin and 3-bromoverongiaquinol: addition of carbon nucleophiles to cyclic oxonum ions under solvent-free conditions

Author(s)

Luiz Antonio Fonseca de Godoy Junior

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Química
• Defense date: 2006-11-30

Examining board members

Ronaldo Aloise Pilli; Roberto Gomes de Souza Berlinck; Paulo Mitsuo Imamura

• Advisor: Ronaldo Aloise Pilli

Abstract

This dissertation is divided in two parts. The first part presents the synthesis of natural products isolated from marine sponges. The second part presents investigations on the addition of carbon nucleophiles to cyclic N-acyliminium and oxonium ions under solvent-free conditions. The natural product 5-monobromocavernicolin was isolated for the first time from the marine sponge Aplysina cavernicola by Pietra and collaborators in 1984. The same compound was recently isolated by Berlinck and collaborators from the sponge Aplysina fulva. 5-monobromocavernicolin was the first compound isolated from a marine organism in a quasi-racemic form (6% ee). The compound 3-bromoverongiaquinol was also isolated from the marine sponge Aplysina cavernícola and biological studies showed that both compounds presents bactericidal activity. In the present investigation, the synthesis of 5-monobromocavernicolin was carried out by 1 ,2 addition of the BSA lithium enolate to 1,4-benzoquinone, to give the product in 56% yield. A bromation reaction was carried out with bromine and the purification of the corresponding product by silica gel column chromatography promoted elimination of HBr, provinding 3-bromoverongiaquinol in 50% of global yield from 1,4-benzoquinone. It's worth to mention that this yield is superior compared to those already reported in the literature (2,5 e 6,3%). The crude product of the bromation reaction was then cyclized in alkaline medium resulting in the formation of 5-monobromocavernicolin. The second part of this dissertation describes the preparation of tetrahydrofurans and tetrahydropyrans with substituents adjacent to the ring oxygen atom. Related compounds are frequently found in several biologically active natural products. The addition reaction of carbon nucleophiles to oxonium ions were investigated in the presence of InCl3 (20 mol%) and under solvent free conditions, an environmentally friendly procedure. It was observed that nucleophiles with higher p a values promote faster addition reaction in higher yields (AU)