Xanthen-9-ylidene protecting groups in glycerol chemistry
Colin B. Reese * and Hongbin Yan Department of Chemistry, King's College London, Strand, London, UK WC2R 2LS. E-mail: colin.reese@kcl.ac.uk; Fax: 44(0)20 7848 1771 Received (in Cambridge, UK) 30th March 2001, Accepted 29th May 2001 First published as an Advance Article on the web 16th July 2001
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PERKIN
The preparation of racemic, (S )- and (R)-1,2-O-(xanthen-9-ylidene)glycerol 17a, 20a and 23a and racemic, (S )and (R)-1,2-O-(2,7-dimethylxanthen-9-ylidene)glycerol 17b, 20b and 23b is reported. The racemic derivatives 17a and 17b are converted into their stearate esters, which are then treated with dichloroacetic acid and pyrrole under mild conditions to give racemic 1-O-stearoylglycerol 25 in good yield. The xanthen-9-ylidene and 2,7-dimethylxanthen-9-ylidene residues are incorporated into 9,9-di(pyrrol-2-yl)xanthene 36 and 2,7-dimethyl-9,9-di(pyrrol2-yl)xanthene 37. These by-products are easily removed by treatment with iron() chloride in diethyl ether solution. What are believed to be enantiomerically pure (R)- and (S )-1-O-stearoylglycerol 28 and 5 are similarly prepared in good yields from (S )- and (R)-1,2-O-(xanthen-9-ylidene)glycerol 20a and 23a.
Introduction
(S )- and (R)-2,3-O-Isopropylideneglyceraldehyde 1 and 2 are valuable chiral building blocks that are both relatively easy to prepare 1,2 in high enantiomeric excess. This is also true of (R)- and (S )-1,2-O-isopropylideneglycerol 3 and 4 which may readily be obtained 3 by the sodium borohydride reduction of the corresponding glyceraldehyde derivatives 1 and 2. Recently, in connection with our work on the synthesis of phosphatidylinositol 3,4,5-trisphosphate 4,5 [PtdIns(3,4,5)P3], we needed to prepare (S )-1-O-stearoylglycerol 5. The acidic conditions required 5,6 for the unblocking of its precursor isopropylidene derivative 6 were relatively drastic and hence the possibility of acyl migration occurring to a small extent (probably not more than 1%) and consequent racemization could not be ruled out. We therefore decided to undertake the preparation of chiral building blocks corresponding to the isopropylidene derivatives 3 and 4, but involving an achiral acetal protecting group that was more labile to acidic hydrolysis than the isopropylidene group.

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