(DBU) flowed by methyl iodide leads to the corresponding methyl ester 11.
Heating 11 with ethylamine leads to ester interchange and formation of the
ethyl amidebimatoprost( 12 ).^4
HOOH OHCO 2 H10HOOH OHCO 2 CH 311HOOH OHCO 2 NHC 2 H 512DBU
CH 3 IC 2 H 5 NH 2A PGE related compound,lubiprostone( 23 ) displays a quite different
spectrum of activity. This compound has been recently approved for treat-
ment of chronic constipation and is being investigated for its effect on
constipation-predominant irritable bowel syndrome. It has been ascertained
that the drug interacts with specific ion channels in the GI tract causing
increased fluid output into the lumen. Starting material for the synthesis
( 13 ) comprises yet another variant on the Corey lactone. Condensation
OOTHPO CH=O
13+
OF F
P
OHH 33 CCOOOOTHPO OF F14 15OOTHPO OF F16H 2
OOTHPO OHF F17OOHTHPO OF F18DiBAL NaBH 4(C 6 H 5 ) 3 P+(CH 2 ) 3 CO 2 –OHTHPO O
F19FCO 2 HOHTHPO OF
20FCO 2 CH 2 C 6 H 5 1. CrO^3- AcOH
OHO OF
21FCO 2 CH 2 C 6 H 5OHO OFFH 2
CO 2 HOFFCO 2 H22O
HO
23tBuOK24 ALICYCLIC COMPOUNDS