Vitamin d3 lactone derivatives

A process for synthesizing a compound represented by the following Formula (4syn), wherein the relative configuration of carbon a and carbon b is syn,

• comprising reacting, in the presence of divalent chromium, an aldehyde compound represented by the following Formula (2):
• [wherein Z refers to any one of Formulas (2-1), (2-2), (2-3), (2-4) and (2-5):
• wherein Y refers to bromine atom or iodine atom;
• R3 refers to trimethylsilyl group, triethylsilyl group, triisopropylsilyl group, t-butyldimethylsilyl group, t-butyldiphenylsilyl group, acetyl group, benzoyl group, methoxymethyl group or tetrahydro-4H-pyran-2-yl group;
• R4 or R5 independently refers to methyl group, ethyl group, propyl group, trichloroethyl group, or R4 and R5 are combined to refer to ethylene group or propylene group, X refers to oxygen atom or sulfur atom;
• R6 refers to hydrogen atom, C1-C6 alkyl group optionally substituted with a hydroxyl group protected by a group defined by R3, or C1-C6 alkoxy group optionally substituted by a hydroxyl group protected by a group defined by R3], with an acrylic acid derivative represented by the following Formula (3),
• [wherein R2c refers to C1-C10 alkyl group optionally substituted with hydroxyl group protected by a group defined by R3 of the above Formula (2), C6-C10 aryl group optionally substituted with hydroxyl group protected by a group defined by R3 of the above Formula (2), or C7-C12 aralkyl group optionally substituted with hydroxyl group protected by a group defined by R3 of the above Formula (2), and R7 refers to C1-C6 alkyl group],
• wherein R2c in the above Formula (4syn) has the same definition as in the above Formula (3), and Z in the above Formula (4syn) has the same definition as in the above Formula (2).

A process which comprises, in the following order, the steps of:

• reducing a lactone ring of a lactone compound represented by the following Formula (4syn),
• [wherein R2c has the same definition as in the above Formula (3), Z has the same definition as in the above Formula (2), and the relative configuration of carbon a and carbon b is syn];
• protecting the resultant primary hydroxyl group to obtain an alcohol compound represented by the following Formula (5syn),
• [wherein R2c has the same definition as in the above Formula (3), Z has the same definition as in the above Formula (2), R8 refers to acetyl group, 4-oxopentanoyl group, pivaroyl group, benzoyl group, triisopropylsilyl group, t-butyldimethylsilyl group or t-butyldiphenylsilyl group and the relative configuration of carbon a and carbon b is syn];
• oxidizing the secondary hydroxyl group of the alcohol compound to obtain a ketonic compound represented by the following Formula (6),
• [wherein R2c has the same definition as in the above Formula (3), Z has the same definition as in the above Formula (2), and R8 has the same definition as in the above Formula (5syn)];
• reducing the ketone group of the ketonic compound to obtain an alcohol compound represented by the following Formula (5anti),
• [wherein R2c has the same definition as in the above Formula (3), Z has the same definition as in the above Formula (2), R8 has the same definition as in the above Formula (5syn), and the relative configuration of carbon a and carbon b is syn];
• and
• deprotecting R8 of the alcohol compound and then oxidizing the resultant primary hydroxyl group to form a lactone ring,
• for synthesizing a lactone compound represented by the following Formula (4anti),
• [wherein, R2c has the same definition as in the above Formula (3), Z has the same definition as in the above Formula (2), and the relative configuration of carbon a and carbon b is anti].

A lactone compound represented by the following Formula (4),

• [wherein R2d and R2e refer to C1-C10 alkyl group optionally substituted with hydroxyl group protected by the group defined by R3 of the above Formula (2);
• C6-C10 aryl group optionally substituted with hydroxyl group protected by the group defined by R3 of the above Formula (2);
• or C7-C12 aralkyl group optionally substituted with a hydroxyl group protected by the group defined by R3 of the above Formula (2);
• or alternatively, R2d and R2e may be combined together to form a cyclopropane ring together with the carbon atom to which R2d and R2e are bonded;
• and Z has the same definition as in the above Formula (2)].