Method for preparing prostaglandin derivative
A method for preparing a prostaglandin derivative represented by the following general formula (I): (wherein Ph represents phenyl group, R 1 represents a C 1-7 alkyl group, a C 1-7 alkenyl group, phenyl group, or benzyl group), which comprises the successive steps (1) to (8) described in the specification, or any one step or two or more successive steps selected from the group consisting of the steps (1) to (8). A method for efficiently, inexpensively and safely preparing prostaglandin derivatives, of which typical example is latanoprost, is provided.
1. A method for preparing a prostaglandin derivative represented by the following general formula (I):
wherein Ph represents phenyl group, R 1 represents a C 1-7 alkyl group, a C 1-7 alkenyl group, phenyl group, or benzyl group, which comprises:
(1) converting a compound represented by the following formula (II), wherein
X represents a protective group selected from the group consisting of an aroyl group having 0 to 3 substituents, a trialkylsilyl group, and a triarylsilyl group, wherein the substituents of the aroyl group are selected from the group consisting of a halogen atom, a C 1-6 alkyl group and a C 6-12 aryl group into a compound represented by the following formula (IV) by oxidizing the compound of the formula (II) into an aldehyde and then reacting the aldehyde with a phosphonic acid ester represented by the following formula (III) (R 2 represents a C 1-6 alkyl group or a C 6-12 aryl group);
(2) converting the compound represented by the following formula (IV) into a compound represented by the following formula (V) by reducing the oxo group on the side chain of the compound of the formula (IV) using (S)-1,1′-binaphthyl-2-2′-dioxyaluminum hydride as a reducing agent;
(3) converting the compound represented by the following formula (V) into a compound represented by the following formula (VI) by hydrogenating the compound of the formula (V);
(4) converting the compound represented by the following formula (VI) into a compound represented by the following formula (VII) by removing the protective group X of the compound of the formula (VI);
(5) converting the compound represented by the following formula (VII) into a compound represented by the following formula (VIII) by protecting the hydroxyl groups of the compound of the formula (VII) with protective groups P, wherein the protective group P is a tetrahydropyranyl group;
(6) converting the compound represented by the following formula (VIII) into a compound represented by the following formula (IX) by reducing the oxo group on the lactone ring of the compound of the formula (VIII);
(7) converting the compound represented by the following formula (IX) into a compound represented by the following formula (X) by reacting the compound of the formula (IX) with a 4-carboxybutyltriphenylphosphonium halide; and
(8) converting the compound represented by the following formula (X) into a compound represented by the following formula (XI) by esterifying the carboxyl group of the compound of the formula (X) and then removing the protective groups P:
(in the above formulas (III) to (XI), Ph represents phenyl group).
2. The method according to claim 1 , wherein X is a benzoyl group.
3. The method according to claim 1 , wherein R 1 is an isopropyl group.
4. The method according to claim 2 , wherein R 1 is an isopropyl group.