Conversion of Tomato Saponins to Pregnane Derivatives

Abstract

Here reports new conversions methods of tomato saponins, esculeoside A (1) and a mixture of esculeosides B-1 (2) and B-2 (3), (the latter two were obtained from tomato cans) into pregnane derivative (5) by an alkal treatment followed by acid treatment. Compound 1 or a mixture of 2 and 3 were each refluxed with 1 N KOH to afford a characteristic pyridine steroidal glycoside (4), which was then treated with 2 N HCl-MeOH to afford a pregnane derivative, 3β-hydroxy-5α-pregn-16-en-20-one (5). The results of the above two reactions indicated that tomato saponins are chemically closely related to pregnane hormones. We assume that the assimilated tomato saponins via the small intestine are metabolized into pregnane derivatives, demonstrating various bioactivities such as anti-cancer, anti-osteoporosis, and anti-menopausal disorder activities.Key words tomato saponin; esculeoside A; esculeoside B; alkali treatment; pyridine steroidal derivative; pregnane In 2003, Nohara and colleagues isolated a tomato saponin, named as esculeoside A (1), 1,2) from the mature fruits of tomato, Solanum lycopersicum L., and determined its structure. Tomato saponin is a significant constituent of ripe tomatoes and is present in approximately four-fold higher levels than lycopene. Thus far, the bioactivity of tomato has been attributed solely to lycopene. Therefore, the pharmacological evaluation of 1 is important.Recently, Fujiwara et al. 3) reported that the oral administration of 1 to apolipoprotein E-deficient mice significantly reduced the serum levels of cholesterol glycerides, low-density lipoprotein cholesterol, and the severity of atherosclerotic lesions without any detectable side effects. In addition, we found an interesting chemical conversion: esculeogenin A, the sapogenol of 1, was easily converted to a pregnane derivative, 3β-hydroxy-5α-pregn-16-ene-20-one (5), by refluxing in aqueous pyridine, 4,5) as shown in Chart 1, indicating that tomato saponin is closely related to the pregnane hormone from the viewpoint of chemical reaction.Furthermore, we found a new method for the respective conversions of 1 or a mixture of esculeosides B-1 (2) and B-2 (3) 6) to the pregnane derivative as follows: Esculeoside A (1) was refluxed in 1 N KOH for 1 h. The reaction mixture was separated by silica gel column chromatography using a mixture of CHCl 3 -MeOH-H 2 O (8 : 2 : 0.2) to afford the major product (4), amorphous powder, [α] D