Ana Gradillas

Morita-Baylis-Hillman reaction of lactams and lactones with alkyl halides and epoxides catalyzed by hydroxysulfides.

A new Morita-Baylis-Hillman reaction methodology in which alkyl halides and epoxides act as electrophiles in their reaction with lactones and lactams is shown. Catalysis is efficiently performed by hydroxy sulfides under basic conditions. The procedure works efficiently with many alkyl halides but fails with aldehydes with which a conventional acid-catalyzed procedure is used.

New synthesis and promising neuroprotective role in experimental ischemic stroke of ONO-1714

In an experimental permanent stroke model, we report here the contribution of ONO-1714 to brain damage prevention. Daily drug administration, twenty-one days prior to and two days after an experimental infarct, was performed by using mini-osmotic pumps (ALZET). Infarct volumes were assessed by image analysis of sequential coronal brain 1 mm(3) sections stained following the 2,3,5-triphenyltetrazolium chloride histological staining technique. Results of this study provide evidence of a significant reduction of the brain lesion size, suggesting ONO-1714 as a potential neuroprotective agent in stroke patients. ONO-1714 was prepared in our laboratory following a procedure which resulted in the supply of the desired compound in an easy and excellent yield.

Synthesis of Macrocycles Other than Peptides by Metathesis

Metathesis is one of the most efficient methodologies for the synthesis of large heterocycles. The wide variety of densely functionalized natural structures containing macrocycles and the interest of other nonnatural macrocycles as potential drugs or useful structures for supramolecular chemistry has triggered the synthetic efforts en route to these structures. This chapter is an overview of successful metathesis reactions, both diene ring-closing metathesis (RCM) and ring-closing alkyne metathesis (RCAM) as the key steps in the construction of large heterocycles (12 or more members excluding peptides). The focus will be made on the different conditions that may favor the metathesis process including substrate design, catalyst nature, and reaction conditions.