Synthesis of Sphingosine‐1‐phosphonate and Homosphingosine‐1‐phosphonate

Abstract In the first approach to homosphingosine‐1‐phosphonate, D ‐glucofuranose was selectively deoxygenated at C‐5. Bond cleavage between C‐1 and C‐2 afforded a 5‐deoxy‐ D ‐ threo ‐pentose intermediate. ( E )‐Selective Wittig reaction with a C 14 ‐chain gave a C 19 ‐intermediate, which was readily transformed into homosphingosine. Formation of a cyclic urethane containing the 3‐amino and the 4‐hydroxy group of the C 19 ‐intermediate permitted regioselective introduction of the phosphonate group at C‐1, thus affording the target molecule after deprotection. In a second and shorter route, C 18 ‐sphingosine was converted to a cyclic urethane containing the 2‐amino and the 3‐hydroxy group of the C 18 ‐chain. C 1 ‐Chain extension by a hydroxymethyl group by introduction of cyanide led to the same C 19 cyclic urethane as obtained in the first route. Similarly, the C 18 cyclic urethane led to the other target molecule, namely sphingosine‐1‐phosphonate. The third and shortest route to homosphingosine‐1‐phosphonate could be based on regioselective 1‐ O ‐tosylation of 1,2,3‐(trihydroxy)octadec‐4‐ene. Transformation into a 1,2‐epoxide, then combination of C 1 ‐chain extension and introduction of a phosphonate group with methylphosphonate as reagent, and finally azide introduction, led after functional group liberation to the target molecule. As shown, also truncated derivatives are readily accessible by this route. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)