SYNTHESIS OF LABDANE DERIVED PAF ANTAGONISTS

Synthesis of novel labdane derived platelet activating factor antagoni st has been achieved. The starting compounds in the syntheses are 1,9- dideoxy-7-deacetylforskolin1 (1), -tert-butyl(dimethyl)silyloxy-7-deac etylforskolin2 (2) and l(dimethyl)silyloxy-(DELTA5,6-7-deacetylforskol in3 (15). All the above three compounds have been separately condensed with epibromohydrin to give coupling products at position-7, viz. 1a, 2a and 15a respectively. The epoxide ring of the side chain gets open ed in the presence of amberlyst XN. 1010 and water to diols 3, 4 and 1 6a respectively. The primary OH group of the side chain in all the int ermediates is tritylated and the free secondary OH group is either met hylated or acetylated to give the corresponding methyl ether and acety l derivatives. These. derivatives are elaborated after a series of dep rotection, followed by reaction with 2-chloro-2-oxo- 1,3,2-dioxaphosph olane to the corresponding phosphocholine target compounds 23, 24, 25, 26 and 28. Compounds 27 and 31 have been prepared by hydrogenating co mpounds 23 and 25 respectively. Out of nine final compounds, compounds 23, 28, 30a and 31 show PAF antagonistic activity.