Preparation of optically pure 4-(hydroxymethyl)-2-pentadecyl-1,3-dioxolanes and their corresponding phosphodiester ether lipid derivatives.
Semi-preparative HPLC on a chiral stationary phase (Chiracel OD) was utilized in the course of this synthesis to separate the four possible diastereomers [cis-(2R,4S)-2a, trans-(2S,4S)-2b, cis-(2S,4R)-2a', and trans-(2R,4R)-2b'] of a 2,4-disubstituted-1,3-dioxolane into optically pure forms (100% de, 100% ee). The syntheses of phosphodiester head group derivatives from each of these four conformationally constrained diastereomeric dioxolanes gave phospholipids which are monocyclic ether lipid analogs. First, the series of four [[(2-pentadecyl-1,3-dioxolan-4-yl)methyl]oxy]phosphocholines 5 were synthesized to give optically pure conformationally constrained analogues of ET-16-OCH(3). A head group variation was also demonstrated by the syntheses of the four diastereomeric [[(2-pentadecyl-1,3-dioxolan-4-yl)-methyl]oxy]phospho-beta-(N-methylmorpholino)ethanols 6.
Lin
S
S
School of Pharmacy, U-92, University of Connecticut, Storrs, CT 06269, USA.
Duclos
R I
RI
Makriyannis
A
A
D002626:Chemistry, Pharmaceutical; D004148:Dioxolanes / Q000138:chemical synthesis* / Q000737:chemistry; D015195:Drug Design; D009904:Optical Rotation; D010742:Phospholipid Ethers / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D004148:Dioxolanes; D010742:Phospholipid Ethers