ステロールを用いる生物活性化合物の合成と構造活性相関

Abstract

Sterols are widely and abundantly distributed in nature. It is convenient to utilize them for the preparation of useful compounds such as pharmaceuticals with steroid and secosteroid skeletons. This paper describes the synthesis and structure-activity relationships of naturally occurring active forms of vitamin D analogues, sterols having neurite outgrowth activity, and liver X receptor agonist. The active form of vitamin D 4 showed similar biological activities but had higher a‹nity to the vitamin D-binding protein compared with the corresponding vitamins D 2 and D 3 . This shows that the active form of vitamin D 4 is a good candidate for an agent to replace the active forms of vitamins D 2 and D 3 . In the course of screening for low molecular-weight compounds that exhibit neurite outgrowth activity in the culture broth, we found that the natural product dictyosterol showed strong activity. From screening of the analogues, it was found that the double bond between C22 and C23 in the side chain of the sterol is essential for its activity. Ergost-22-ene-1a,3b-diol was found to serve as a stronger liver X receptor agonist than 24(S), 25-epoxycholesterol, which regulates the expression of genes involved in lipid metabolism. Structure-function study showed that the 1a-hydroxyl group, the saturated steroid structure, and the double bond between C22 and C23 are needed to function as a liver X receptor agonist. しかし，1 はその強い毒性（カルシウム上昇作

Identification of a Novel Dehydroergosterol Enhancing Microglial Anti-Inflammatory Activity in a Dairy Product Fermented with Penicillium candidum

“…Inspection of these two chemical structures suggests that the conjugated double bond system is essential for anti-inflammatory activity. Ergosterol, which is known as provitamin D2, is particularly abundant in fungi as well as being present in bacteria and plants [22]. However, DHE, discovered in the present study, is found only in P .…”

Antibacterial compounds from shoot skins of moso bamboo (Phyllostachys pubescens)

“…Also, β-sitosterol (3) has no double bond between C22 and C23, and an ethyl group attaches to C24. It has been reported that some steroidal compounds express thier biological activities in vivo, caused by the reaction between their double bonds in the side chain and protein or peptide [17]. Considering its possibility, stigmasterol (1) may express its antibacterial activity by the similar way.…”

Preventive Effects of Dairy Products on Dementia and the Underlying Mechanisms

“…Dehydroergosterol was also discovered as a component of Camembert cheese that suppressed microglial inflammation. Dehydroergosterol is an analogue of ergosterol, which is a sterol found in the cell membrane of fungi [ 69 , 70 ] ( Figure 1 ). Dehydroergosterol is generated by fungi during fermentation.…”