Efficient synthesis of sphingosine-1-phosphate, ceramide-1-phosphate, lysosphingomyelin, and sphingomyelin

✍ Scribed by Kratzer, Bernd ;Schmidt, Richard R.

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 839 KB
• Volume: 1995
• Category: Article
• ISSN: 0947-3440
• DOI: 10.1002/jlac.1995199506137

✦ Synopsis

Abstract

Readily available D‐erythro‐azidosphingosine is transformed into 3‐O‐silyl‐protected derivative 6. Reduction of the azido group afforded 3‐O‐silyl‐protected sphingosine 7 which was either converted into N‐Fmoc‐protected derivative 8 or via N‐acylation into ceramide derivatives 16 and 17, respectively. Treatment of 6, 8, and 16 with bis(2‐cyanoethoxy)(diiso‐propylamino)phosphane as monofunctional phosphitylating agent, subsequent oxidation and then removal of the protective groups furnished azidosphingosine‐1‐phosphate (11), sphingosine‐1‐phosphate (2), and ceramide‐1‐phosphate (4), respectively. Treatment of 8 and 17 with bis(diisopropyl‐amino)(2‐cyanoethoxy)phosphane as bifunctional phosphitylating agent and then with choline afforded after oxidation and subsequent deprotection lysosphingomyelin (3) and sphingomeylin (1), respectively in high overall yields. All final products are stereochemically pure and possess D‐er‐ythro configuration in the sphingosine moiety.