Method For Preparing Indene Derivatives, And Intermediates For Preparation Of Derivatives
Indene derivatives that are utilizable as intermediates in the synthesis of the vitamin D 2 derivative paricalcitol, which is useful as pharmaceutical are efficiently prepared by subjecting a vitamin D 2 derivative such as 25-hydroxyvitamin D 2 to a two-steps oxidation reaction using an oxidizing agent such as potassium permanganates and sodium periodate in a suitable solvent such as methanol and ethanol.
1 : A method of preparing an indene derivative denoted by formula (III)
(in formula (III), R 1 denotes a hydrogen atom or a protective group for a hydroxyl group), characterized by comprising oxidizing a vitamin D 2 derivative denoted by formula (V)
(in formula (V), both X 1 and X 2 denote hydroxyl groups or jointly form an epoxy group, and each of R 1 and R 2 independently denotes a hydrogen atom or a protective group for a hydroxyl group).
2 : The preparing method in accordance with claim 1 , wherein the oxidation of the vitamin D 2 derivative denoted by formula (V) is conducted in solvent with an oxidizing agent.
3 : The preparing method in accordance with claim 1 , wherein the protective groups for hydroxyl groups denoted by R 1 and R 2 are silyl groups, alkoxymethyl groups, aralkyloxymethyl groups, or acyl groups.
4 : The preparing method in accordance with claim 1 , wherein the protective groups for hydroxyl groups denoted by R 1 and R 2 are trimethylsilyl groups, triethylsilyl groups, methoxymethyl groups, benzyloxymethyl groups, or acetyl groups.
5 . The preparing method in accordance with claim 1 , wherein the vitamin D 2 derivative denoted by formula (V) is 7,8,25-trihydroxyvitamin D 2 denoted by formula (II)
6 : The preparing method in accordance with claim 1 , wherein the vitamin D 2 derivative denoted by formula (V) is prepared by oxidizing the vitamin D 2 derivative denoted by formula (IV)
(in formula (IV), both R 1 and R 2 are defined as in formula (V))
7 : The preparing method in accordance with claim 6 , wherein the oxidation of the vitamin D 2 derivative denoted by formula (IV) is conducted in solvent with an oxidizing agent.
8 : The preparing method in accordance with claim 5 , wherein the 7,8,25-trihydroxyvitamin D 2 denoted by formula (II) is prepared by oxidizing the 25-hydroxyvitamin D 2 denoted by formula (I)
9 : A method of preparing a vitamin D 2 derivative denoted by formula (V)
(where in formula (V), both X 1 and X 2 denote hydroxyl groups or jointly form an epoxy group, and each of R 1 and R 2 independently denotes a hydrogen atom or a protective group for a hydroxyl group), characterized by comprising the step of oxidizing the vitamin D 2 derivative denoted by formula (IV)
(in formula (IV), both R 1 and R 2 are defined as in formula (V))
10 : The preparing method in accordance with claim 9 , wherein the oxidation of the vitamin D 2 derivative denoted by formula (IV) is conducted in solvent with an oxidizing agent.
11 : The preparing method in accordance with claim 9 , wherein the protective groups for hydroxyl groups denoted by R 1 and R 2 are silyl groups, alkoxymethyl groups, aralkyloxymethyl groups, or acyl groups.
12 : The preparing method in accordance with claim 9 , wherein the protective groups for hydroxyl groups denoted by R 1 and R 2 are trimethylsilyl groups, triethylsilyl groups, methoxymethyl groups, benzyloxymethyl groups, or acetyl groups.
13 : The preparing method in accordance with claim 9 , wherein the vitamin D 2 derivative denoted by formula (V) is the 7,8,25-trihydroxyvitamin D 2 denoted by formula (II)
and the vitamin D 2 derivative denoted by formula (IV) is the 25-hydroxyvitamin D 2 denoted by formula (I)
14 : A vitamin D 2 derivative denoted by formula (V)
(in formula (V), both X 1 and X 2 denote hydroxyl groups or jointly form an epoxy group and each of R 1 and R 2 independently denotes a hydrogen atom or a protective group for a hydroxyl group).
15 : The derivative in accordance with claim 14 , wherein the protective groups for hydroxyl groups denoted by R 1 and R 2 are silyl groups, alkoxymethyl groups, aralkyloxymethyl groups, or acyl groups.
16 : The derivative in accordance with claim 14 , wherein the protective groups for hydroxyl groups denoted by R 1 and R 2 are trimethylsilyl groups, triethylsilyl groups, methoxymethyl groups, benzyloxymethyl groups, or acetyl groups.
17 : The derivative in accordance with claim 14 , wherein R 1 and R 2 denote hydrogen atoms.
18 : The derivative in accordance with claim 14 , wherein X 1 and X 2 both denote hydroxyl groups and R 1 and R 2 denote hydrogen atoms.
19 : A method of preparing an indene derivative denoted by formula (III)
(in formula (III), R 1 denotes a hydrogen atom or a protective group for a hydroxyl group), characterized by comprising oxidizing the vitamin D 2 derivative denoted by formula (IV)
(where in formula (IV), each of R 1 and R 2 independently denotes a hydrogen atom or a protective group for a hydroxyl group).
20 : The preparing method in accordance with claim 19 , wherein the oxidation of the vitamin D 2 derivative denoted by formula (IV) is conducted in solvent with an oxidizing agent.
21 : The preparing method in accordance with claim 19 , wherein the protective groups for the hydroxyl groups denoted by R 1 and R 2 are silyl groups, alkoxymethyl groups, aralkyloxymethyl groups, or acyl groups.
22 : The preparing method in accordance with claim 19 , wherein the protective groups for the hydroxyl groups denoted by R 1 and R 2 are trimethylsilyl groups, triethylsilyl groups, methoxymethyl groups, benzyloxymethyl groups, or acetyl groups.