(+)- and (−)-syn-2-Isobutyl-4-methylazetidine-2,4-dicarboxylic Acids from the Extract of Monascus pilosus-Fermented Rice (Red-Mold Rice).

Abstract

Tadahiko Fukuoka: (+)-and (-)-syn-2-Isobutyl-4-methylazetidine-2,4-dicarboxylic Acids from the Extract of Monascus pilosus-Fermented Rice (Red-Mold Rice).

Azaphilones, Furanoisophthalides, and Amino Acids from the Extracts of Monascus pilosus-Fermented Rice (Red-Mold Rice) and Their Chemopreventive Effects

“…Six azaphilones were isolated from the EtOAc soluble fraction of a 70% EtOH extract of red-mold rice and identified as monascin (1), ankaflavin (2), rubropunctatin (3), monascorubrin (4), rubropunctamine (5), and monascorubramine (6). In addition, two furanoisophthalides isolated from the acidic MeOH extract of red-mold rice were identified as xanthomonasin A (7) and xanthomonasin B (8). These eight compounds (1-8), along with two amino acids (9 and 10) recently isolated (8), were evaluated for their inhibitory effects on TPA-induced inflammation in mice, on the induction of EBV-EA by TPA in Raji cells, and on the activation of NOR 1, a NO donor.…”

“…Red-mold rice was prepared from cooked paddy rice inoculated with Monascus pilosus IFO 4520, obtained from the Institute for Fermentation (IFO), Osaka, Japan, as described previously (6). (+)-Monascumic acid ( 9) and (-)-monascumic acid (10) were isolated from red-mold rice recently (8). The following chemicals were purchased: TPA from ChemSyn Laboratories (Lenexa, KS), indomethacin, β-carotene, and glyzyrrhizin from Sigma Chemical Co. (St. Louis, MO), the EBV cell culture reagents and n-butyric acid from Nacalai Tesque, Inc. (Kyoto, Japan), and NOR 1 and carboxy-PTIO from Dojindo Laboratories (Kumamoto, Japan).…”

“…γ-Aminobutyric acid (GABA) (6), possessing antihypertensive effects for humans, and monacolin K (lovastatin; mevinolin) (3), which functions as an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, have been isolated from red-mold rice. In the course of our search for potential antitumor-promoters from natural sources (7), we have isolated and characterized two new azetidine-type amino acids, (+)- [9; (+)-monascumic acid] and (-)-syn-2-isobutyl-4methylazetidine-2,4-dicarboxylic acids [10; (-)-monascumic acid], from the extract of red-mold rice fermented with Monascus pilosus (8). In this paper, we report the isolation and characterization of further eight compounds (1)(2)(3)(4)(5)(6)(7)(8) from the red-mold rice extracts and the inhibitory effects of 10 compounds (1-10) (Figure 1) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice, on the induction of Epstein-Barr virus early antigen (EBV-EA) by TPA, and on activation of (()-(E)-methyl-2[(E)-hydroxy-imino]-5-nitro-6methoxy-3-hexemide (NOR 1), a nitric oxide (NO) donor.…”

“…In the course of our search for potential antitumor-promoters from natural sources (7), we have isolated and characterized two new azetidine-type amino acids, (+)- [9; (+)-monascumic acid] and (-)-syn-2-isobutyl-4methylazetidine-2,4-dicarboxylic acids [10; (-)-monascumic acid], from the extract of red-mold rice fermented with Monascus pilosus (8). In this paper, we report the isolation and characterization of further eight compounds (1)(2)(3)(4)(5)(6)(7)(8) from the red-mold rice extracts and the inhibitory effects of 10 compounds (1-10) (Figure 1) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice, on the induction of Epstein-Barr virus early antigen (EBV-EA) by TPA, and on activation of (()-(E)-methyl-2[(E)-hydroxy-imino]-5-nitro-6methoxy-3-hexemide (NOR 1), a nitric oxide (NO) donor. Compounds 1-6 along with a new nonpigment, monascodilone, and citrinin have recently been detected in the red-mold rice obtained as cultures of M. purpureus DSM1379 on rice (9).…”

Amino acid–azetidine chimeras: synthesis of enantiopure 3‐substituted azetidine‐2‐carboxylic acids

“…A component of biologically and pharmacologically important natural products and synthetic compounds, Aze has been found in the polyoxin group of antifungal antibiotics (21), nicotianamine (22), mugineic acid (23), and red‐mold rice fermentation products (24). Among substituted azetidine carboxylic acid analogs, cis ‐azetidine‐2,4‐dicarboxylic acid has been reported as a neurotransmitter potentiator (25,26) and trans ‐2‐carboxyazetidine‐3‐acetic acid ( t ‐CAA) has been used as a rigid glutamic acid analog exhibiting effects such as inhibition of Na + ‐dependent Glu uptake and neuroexcitatory activity at the kainate receptor subtype (26).…”