To provide a method for producing a fluorine-containing prostaglandin derivative having high activities as a medicine and further having fluorine atom at 15-position having no side effect by allowing specific phosphoranes to act on a specified fluorine-containing lactols.
Alcohols of formula I (A is ethylene, etc.; R1 is a 3-8C alkyl, etc.; R3 is H or a protecting group of OH) is fluorinated by a trifluorinated dialkylaminosulfur derivative, which is a nucleophilic fluorinating agent, etc., e.g. morpholinosulfur trifluoride to provide fluorine-containing lactones of formula II, and the lactones is reduced by diisobutylaluminum hydride, etc., to provide a fluorine-containing lactones of formula III. The objective compound having a structure of formula V is obtained by reacting 1 equivalent compound of formula III with 0.1-20 equivalents phosphoranes of formula IV [R2 is a protecting group of H or OH; X is CH2, O or S; Z is OR4, etc., (R4 is H, an alkyl, etc.); R10 is an aryl, an alkyl, etc.] by a so-called Wittig-type reaction to provide the objective compound of formula V.
MORI NOBUAKI
SAKATA KAZUHISA
MATSUMURA YASUSHI
MORISAWA YOSHITOMI
