Stereoselective total synthesis of Oxylipin from open chain gluco-configured building block
Highlights
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Total synthesis of naturally occurring Oxylipin has been achieved from gluco-configured building block.
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Grignard reaction and Wittig olefination reaction are key steps for the requisite C
C bond formation. - •
Simple synthetic transformations and easily available starting materials.
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Wide possibility for other analogues of Oxylipin is an additional merit of the developed synthetic route.
Abstract
Total synthesis of naturally occurring Oxylipin has been achieved from open chain gluco-configured building block which is readily assembled from inexpensive and commercially available D-(+)-gluconolactone. Grignard reaction and Wittig olefination reactions are key steps for the requisite CC bond formation.
Introduction
Oxylipins are the naturally occurring lipids derived from fatty acids. They are functioning as important signalling molecules in plants and fungi [1]. In fungi and mammals oxylipins are involved in synthesis of secondary metabolites. Oxylipins are also medicinally important, because of their anti-fungal, anti-bacterial and anti-diabetic activities [2], [3]. Structurally oxylipins are also known as hydroxy fatty acids (HFAs), due presence of extra hydroxy groups and have different physical properties such as higher melting point, viscosity and reactivity as compared to non-hydroxylated fatty acids [4]. In this context, HFAs have been used as precursors for manufacture of polymers, as additives in the manufacture of lubricants, emulsifiers and stabilisers [5].
Pizza et al. isolated four novel oxylipins (1–4) from the extract of corms of the plant D. Loretense (Fig. 1) [6], [6](a). They have studied immunostimulatory effect of these compounds on Human Peripheral Blood Mononuclear Cells (PBMCs). As a result of this study they found that compound 2 exhibits immunostimulatory effect at 10 μM, whereas compound 4 was found to be least reactive towards cell proliferation. To date there is one report available for the synthesis of Oxylipin 4 [6b]. Due to biological importance of these molecules and our own interests in exploring surfactant properties of poly-hydroxylated long chain fatty acids, we undertook synthesis of Oxylipin 4, envisaging use of open chain D-gluco configured building block 5 [7]. The multi-gram quantities of building block 5 are readily accessible in three simple steps from inexpensive and commercially available D-(+)-gluconolactone as the starting material. Grignard reaction onto the morpholine amide was visualised for the incorporation of n-octyl chain, while hexenyl chain was envisaged through Wittig reaction on the latent aldehyde at C-5 carbon of the building block 5 (Fig. 2).
Section snippets
Results and discussion
The addition of heptylmagnesium bromide onto morpholine amide 5 gave the ketone 6 in 85–90%. The absence of any over addition product during addition of Grignard reagents onto morpholine amides has been rationalized in the literature through the participation of ring oxygen [8]. The ring oxygen of 7 has been proposed for chelation in the tetrahedral intermediate 8. This chelation presumably prevents it collapse to the ketone 9 (until aq. work-up) and thereby over-addition product 10 (Scheme 1).
Conclusion
Successful synthesis of naturally occurring Oxylipin 4 from open chain gluco-configured building block 5 has been realized. The morpholine based amide 5 derived from D-(+)-gluconolactone in three steps is the requisite building block. Wittig reaction and Grignard reaction were the key steps for CC bond formation. Simple synthetic transformations and wide possibility in changing the nature of alkyl residues open up great avenues for other analogues of naturally occurring Oxylipin 4 is an
General
For the reaction purposes and column chromatography, distilled and dry solvents were used. For column chromatography, 100–200 mesh size silica gels were used. All the reactions were followed up by a TLC analysis. This was done using precoated ‘MERCK F254’ plates. The spot detection on TLC was done by exposure of plate under UV light or dipping in to the solution of Hanessian's stain followed by charring on hot plate. High resolution NMR experiments were recorded on BRUKER AV 400 FT NMR or AV
Acknowledgements
The authors thank DST New Delhi for funding toward the 400 MHz and 500 MHz NMR spectrometer to the Department of Chemistry, IIT Madras under the IRPHA scheme. S.R.B. is thankful to IIT-Madras for HTRA fellowship.
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