A method for the condensation of boroxazolidones derived from L-valine with aromatic aldehydes, catalysed by 1,5,7-triazabicyclo[4.4.0]dec-5-ene was developed. The preparation and isolation of a series of highly functionalised stable ketimines derived from the reaction of 2,2-diaryl-1,3,2-oxazaborolidin-5-ones with aryl aldehydes is herein described. Several unreported boroxazolidones were prepared by condensation of triethylammonium tetra-arylborates with L-valine in up to 98% yield. The newly synthesised compounds were determined to be moderately cytotoxic against colorectal adenocarcinoma cells, with the best compound in this series having an IC 50 of 76 mM. A brief inspection of the effect of the same compound against human brain astrocytoma cells showed an IC 50 of 268 mM.
IntroductionSynthesis of boron compounds derived from biomolecules such as sugars, amino acids, peptides and nucleic acids has been an extensive and foremost area of research in the last two decades.
1Among other subjects, much interest has been devoted to molecules containing boron-nitrogen bonds. These compounds can possess broad biological activity 2 such as insecticidal, fungicidal, herbicidal and antibacterial properties.3 The ability of several boron compounds, namely those derived from a-amino acids, to interact with tumour cells has opened new venues for their use as part of boron neutron capture therapy.4 The biological properties of chelates containing N-B bonds have also been reported to include apoptotic activity in tumour cells, 5 an ability to disturb calcium channel transporters, 6 inhibition of human neutrophile elastase, 7 and modulation of human phenylalanine hydroxylase activity. Boroxazolidones, a particular kind of N-B bond-containing compounds, generally obtained by reacting a-amino acids with boranes or borinates, were rstly reported in 1962.9 Glycine and L-methionine derivatives were then prepared by the reaction of these amino acids with trialkyl and triaryl boranes in reuxing xylene.9a Since then, several methods for preparation of boroxazolidones with alkyl groups, hydrogens and halogens on boron have been developed. Skoog reported the use of a diaryl alkyl borinate in the condensation with glycine, alanine and leucine 10 and later Neens described the preparation of several a-amino acid derivatives aer reaction with a slight excess of triethylborane or triphenylborane in THF. 11 A different procedure, comprising the reaction of a-amino acids with sodium tetraphenylborate in the presence of hydrochloric acid in water was developed by Baum.12 This procedure was then applied to the preparation of boroxazolidones derived from glycine, alanine, phenylalanine, proline, cysteine and tyrosine in moderate to good yields. The preparation of 2,2-diphenylboroxazolidones is usually achieved by reaction of the a-amino acid with diphenylborinic acid under basic conditions.
5b,13Boroxazolidones have also been employed in organic synthesis. The higher reactivity of the 2,2-dialkyl boroxazolidones towards solvolysis, namely w...
