Derivative of .alpha., .alpha.-trehalose and a process for preparing the same

• US 4,814,436 A
• Filed: 12/08/1986
• Issued: 03/21/1989
• Est. Priority Date: 12/16/1985
• Status: Expired due to Fees

• Current Assignee: SS Pharmaceutical Company Limited
• Original Assignee: SS Pharmaceutical Company Limited
• Inventors: Shibata, Akihiro, Kohya, Hidehiko, Matsuda, Hideaki, Katori, Tatsuhiko
• Primary Examiner(s): GRIFFIN, RONALD
• Application Number:
  US06/938,883
• Time in Patent Office: 834 Days
• Field of Search: 536/17.1, 536/117, 536/119
• US Class Current: 536/17.1
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07H 13/06 Fatty acids
• CPC Class Codes: C07H 15/18 Acyclic radicals, substituted by carbocyclic rings

Abstract

Derivatives of α,α-trehalose-6,6'"'"'-fatty acid diester having phosphoric ester groups in the molecule which are useful as a carcinostatic agent. One of the derivatives may be prepared by reacting diphenylphosphoryl chloridate with a derivative of 2,3,2'"'"',3'"'"'-tetra-O-benzyl-α,α-trehalose-6,6'"'"'-fatty acid diester. Another derivative may be obtained by substituting benzyl groups at 2,3,2'"'"',3'"'"' positions of trehalose with hydrogen atoms.

Claims

1. A derivative of α

,α

-trehalose represented by the following formula (I);

##STR5## wherein R₁ represents an alkyl group having 1-29 carbon atoms, R₂ represents a hydrogen atom or a benzyl group and R₃ represents a hydrogen atom or a phenyl group.

2. A process for preparing a derivative of 2,3,2'"'"',3'"'"'-tetra-O-benzyl-4,4'"'"'-bis-O-(diphenylphosphono)-α

,α

-trehalose-6,6'"'"'-fatty acid diester represented by the formula (Ia);

##STR6## wherein R₁ represents an alkyl group having 1-29 carbon atoms, Bn, represents a benzyl group and Ph represents a phenyl group, which comprises;

reacting a derivative of 2,3,2'"'"',3'"'"'-tetra-O-benzyl-α

,α

-trehalose-6,6'"'"'-fatty acid diester represented by formula (II);

##STR7## wherein R₁ and Bn each have the same meaning as defined above, with a phosphoric ester represented by formula (III);

##STR8## wherein Ph has the same meaning as defined above and Y represents a halogen atom in a solvent in the presence of a base at a temperature of 0°

-50°

C.

3. The process according to claim 2, wherein said base is one or more bases selected from the group consisting of pyridine, picoline, lutidine, collidine, 4-methylaminopyridine, and triethylamine.

4. A process for preparing a derivative of 4,4'"'"'-di-O-phosphono-α

,α

-trehalose-6,6'"'"'-fatty acid diester represented by the formula (Ib);

##STR9## wherein R₁ represents an alkyl group having 1-29 carbon atoms, which comprises;

reducing a derivative of 2,3,2'"'"',3'"'"'-tetra-O-benzyl-4,4'"'"'-bis-O-(diphenylphosphono)-α

,α

-trehalose-6,6'"'"'-fatty acid diester represented by the formula (Ia);

##STR10## wherein R₁ has the same meaning as defined above, Bn represents a benzyl group, and Ph represents a phenyl group with hydrogen in the presence of a reducing catalyst at a temperature in the range of from room temperature to 50°

C.; and

further reducing the compound produced in the first step by hydrogen in the presence of a reducing catalyst at a temperature in the range of from room temperature to 50°

C.

5. The process according to claim 4, wherein said catalyst used in said first reduction step is palladium black or palladium carbon and said catalyst used in said second reduction step is platinum black.

6. The process according to claim 4, wherein each of said catalysts in the first and second reducing steps is present in the reaction in the amount of 0.01-1 part by weight per 1 part by weight of said derivative of 2,3,2'"'"',3'"'"'-tetra-O-benzyl-4,4'"'"'-bis-O-(diphenylphosphono)-α

,α

-trehalose-6,6'"'"'-fatty acid diester.

7. The process according to claim 5, wherein each of said catalysts in the first and second reducing steps is present in the reaction in the amount of 0.01-1 part by weight per 1 part by weight of said derivative of 2,3,2'"'"',3'"'"'-tetra-O-benzyl-4,4'"'"'-bis-O-(diphenylphosphono)-α

,α

-trehalose-6,6'"'"'-fatty acid diester.

8. The process according to claim 4, wherein each of the reduction steps is conducted in a solvent of acetic acid, methanol, ethanol or isopropanol.