[41] Total synthesis of sphingosine and its analogs

The enigmatic nature of the natural membrane lipid sphingosine has intrigued scientists both in medicine and in chemistry for over a century. The revelations of its vast biological importance brought forward via the rapid evolution of enhanced laboratory techniques have increased the pace of researc...

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Veröffentlicht in:Methods in Enzymology 2000, Vol.311, p.458-479
Hauptverfasser: Koskinen, Päivi M., Koskinen, Ari M.P.
Format: Artikel
Sprache:eng
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Zusammenfassung:The enigmatic nature of the natural membrane lipid sphingosine has intrigued scientists both in medicine and in chemistry for over a century. The revelations of its vast biological importance brought forward via the rapid evolution of enhanced laboratory techniques have increased the pace of research on this essential lipid. The Horner-Wadsworth-Emmons (HWE) reaction offers the synthetic organic chemist an efficient tool for construction of a double bond with high trans selectivity. The serine-derived β-ketophosphonate gives access to a large variety of γ-chiral α,β -unsaturated enone structures, which can be prepared with high enantioselectivity by using the modification of the HWE reaction described in this chapter. High diastereoselectivity and regioselectivity in the reduction of enones are highly desired goals. This chapter discusses the way this can be achieved with the right choice of hydride reagent and reaction conditions that properly maximize the internal asymmetric induction from the existing chiral center in the molecule. The sequence of reactions—β-ketophosphonate formation, modified HWE reaction, and diastereoselective reduction—enables the synthetic organic chemist to selectively construct molecules with multiple chiral centers. The riddle of sphingosine synthesis has thus been solved. A multigram synthesis of all four isomers of sphingosine can be achieved; D-erythro and L-erythro isomers are available starting from the natural L-serine, and it can safely be assumed that because D-serine is merely an enantiomer of L-serine that the remaining two isomers, L-erythro-and D-threo-sphingosines, can be synthesized by precisely the same methodology.
ISSN:0076-6879
1557-7988
DOI:10.1016/S0076-6879(00)11100-0