# US 7,612,213 B2 · Compound having antitumor activity and process for producing the same

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- Number: US 7,612,213 B2
- Document ID: US7612213B2
- Status: Granted
- Kind: B2
- Application number: 10/516,743
- Filed: 2003-06-06
- Published: 2005-09-22
- Granted: 2009-11-03
- Earliest claimed: 2002-06-07
- Assignees: Riken
- Inventors: Hiroyuki Osada; Hideaki Kakeya; Yujiro Hayashi
- Web page: https://patentgrep.com/patent/US7612213B2

## CPC

- C07D 491/04: Ortho-condensed systems
- A61K 31/407: condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
- A61P 35/00: Antineoplastic agents
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

A compound represented by the general formula (I): (I) wherein R represents linear, branched, or cyclic alkyl or aryl; a process for producing the compound; and an antitumor agent containing the compound as an active ingredient.

## Claims

### Claim 1

A compound represented by the following general formula (I)
wherein R in the general formula (I) is a tert-butyl group.

### Claim 2

A process for producing a compound represented by the following general formula (I):
wherein R represents a linear, branched, or cyclic alkyl having 2 or more carbon atoms or an aryl group comprising:
(1) reacting tetrahydropyran-2-ol with (ethoxycarbonylethylidene) triphenylphospholane;
(2) protecting a free hydroxyl group of the reaction product from (1);
(3) transforming a hydroxymethyl group of the reaction product from (2) into a formyl group;
(4) reacting the reaction product from (3) with phosphonoacetic acid ester represented by the following general formula (A):
wherein R and X each represent a linear, branched, or cyclic alkyl or aryl group;
(5) reacting the reaction product from (4) with a base and acetaldehyde;
(6) formally dehydrating the reaction product from (5);
(7) deblocking a protecting group of the reaction product from (6);
(8) oxidizing the reaction product from (7);
(9) reacting the reaction product from (8) with phosphonopropionic acid methyl ester represented by the following general formula (B):
wherein X is defined as in (4) above;
(10) reacting the reaction product from (9) with acetonitrile in the presence of a base;
(11) reacting the reaction product from (10) with propanal represented by the following general formula (C):
wherein Y represents a hydroxyl protecting group;
(12) epoxidizing the reaction product from (11);
(13) deblocking a protecting group of the reaction product from (12);
(14) dehydrating a cyano group from the reaction product from (13); and
(15) lactamizing the reaction product from (14).

### Claim 3

A compound represented by the following general formula (III):
wherein R represents a methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-pentyl group or n-hexyl group and Y represents a tert-butyldiphenylsilyl group, a tert-butyldimethylsilyl group, a triethylsilyl group, a group, a dimethylethylsilyl group, a teterahydropyranyl group, an ethoxyethyl group, a methoxymethyl group or a benzyl group.

### Claim 4

A process for producing a compound represented by the following general formula (III):
wherein R represents a linear, branched, or cyclic alkyl or aryl group and Y represents a hydroxyl protecting group, comprising
reacting a compound represented by the following general formula (IV):
wherein R and Y are defined as above for (III),
with a peroxide that steroselectively epoxidizes the compound (IV).

### Claim 5 (depends on 1)

A pharmaceutical composition containing the compound according to claim 1 as an active ingredient and a pharmaceutically acceptable carrier.

### Claim 6 (depends on 2)

The process according to claim 2, wherein R in the general formula (I) is a linear, branched, or cyclic alkyl group having 2 or more carbon atoms.

### Claim 7 (depends on 2)

The process according to claim 2, wherein R in the general formula (I) is a linear, branched or cyclic alkyl group having 2 to 6 carbon atoms.

### Claim 8 (depends on 2)

The process according to claim 2, wherein R in the general formula (I) is a tert-butyl group.