B. Lal et al., SYNTHESIS OF LABDANE DERIVED PAF ANTAGONISTS, Indian journal of chemistry. Sect. B: organic chemistry, including medical chemistry, 33(5), 1994, pp. 415-427
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.