Method of preparing 3-DPA-lactone

Details Method of preparing 3-DPA-lactone Method of preparing 3-DPA-lactone

1993-03-10

1995-02-21

Ivy, C. Warren

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

C07D30512

Patent

active

053917693

DESCRIPTION:

BRIEF SUMMARY
DESCRIPTION

1. Technical Field
The present invention relates to a method of preparing 3-DPA-lactone.
2. Background Art
Recently, in the field of fine chemicals such as medicines, pesticides and so on, a great deal of attention has been focused on glycoside compounds and sugar-analogue compounds which exist naturally as useful biological active substances.
A well-known example of the sugar-analogue compounds is (2S, 4S)-2-hydroxy-4-hydroxymethyl-4-butanolide which is represented by the following formula [5]. The common name for this compound is 3-deoxy pentonic acid lactone, usually abbreviated as 3-DPA-lactone. ##STR1##
3-DPA-lactone is known as an endogenous feeding promoter substance present in the body fluid of animals. For example, as set forth in the following documents, the concentration of 3-DPA-lactone in the blood of a rat increased as the duration of fasting of the rat was increased, thereby indicating that 3-DPA-lactone is a feeding promotor. When the substance was administered to a rat, under normal feeding conditions it was observed that feeding behavior of the rat was induced. No. 4, page 228 Soc. Jpn., 61,2025 (1988)
Therefore, 3-DPA-lactone is an essential substance for making a scientific explanation of feeding behavior of animals including human. The information obtained in the research can be applied widely for development of foods, medicines, and pesticides.
Utilizing its feeding promotion effect, it is possible to promote growth of domestic animals by, for example, mixing the compound into stock feed.
However, 3-DPA-lactone exists in a small amount in nature, and it is difficult to obtain a large amount thereof by extraction from natural material.
Consequently, 3-DPA-lactone must be prepared by a synthetic method. At present, there are two known techniques for preparing 3-DPA-lactone.
One known technique for preparing 3-DPA-lactone L-malic acid having an optical activity as the starting material [O. Uchikawa, N. Okukado, T. Sakata, K. Arase, K. Terada; Bull. Chem. Soc. Jpn., 61,2025 (1988)]. In this method, a vinyl group is introduced to a carbonyl group of (S)-3,4-O-isopropyliden-3,4-dihydroxybutanal by Grignard reaction so as to form the hydroxyl group corresponding to the hydroxyl group at 2-position of 3-DPA-lactone. Then, the vinyl group is oxidatively cleaved using a Sharpless oxidation into a carboxyl group to form .gamma.-lactone.
The other known method for preparing 3DPA-lactone utilizes .gamma.-ribonolactone as the starting material [K. Bock, I. Lundt, C. Pedersen; Acta. Chem. Scand., B 35, 155 (1981)]. In this method, a hydroxy group of .gamma.-ribonolactone is protected by an acetyl group, and then the .gamma.-ribonolactone is subjected to catalytic hydrogenation at high pressure in the presence of palladium carbon which serves as the catalyst. Lastly, after removal of the acetyl group, 3-DPA-lactone is prepared.
However, each of the above-described methods entails the following drawback.
In the synthetic route of the first method proposed by O. Uchikawa et al., the Grignard reaction is not stereoselective, and therefore two types of diasteromers are formed which respect to the hydroxy group at the 2-position. Therefore, it is necessary to separate the two isomers after lactone formation, wherein the yield of the target product having the S configuration of carbon at the 2-position is as low as about 30%. Further, the hydroxyaldehyde having an optical activatity, which is an intermediate, can be obtained through 6 steps from L-malic acid, and the yield thereof is also as low as 25%. In total, it takes 11 steps to prepare 3-DPA-lactone from L-malic acid, and after separation of the diastereomers from each other as set forth above, the overall yield is as low as only 4%.
On the other hand, in the synthetic route of the second method proposed by K. Bock et al., hydrogenation must be carried out at a pressure of as high as 100 atmospheres. Therefore, the; an apparatus used for carrying out the method entails drawbacks in terms of simplicity and safety. In addition, there are m

REFERENCES:
patent: 4859677 (1989-08-01), Borchardt et al.

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