Tricholomic acid

Vinylglycine was used in the reaction with dibromoformaldoxime for preparation of a biologically active bromoisoxazoline 30, prepared previously from tricholomic acid (79JA1054 80TL229). 

N=C(Cl)—,2 A key step in a synthesis of the antimetabolite (aS,5S)-a-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (AT-125, 4) from l-glutamic acid involved reaction of the protected derivative (2) of tricholomic acid with 1 in refluxing THF to give 3 in 54% isolated yield. The protective groups were then removed with TFA-thioanisole in 87% yield. 

Trichlorobenzoyl chloride, 552 Trichloroethylene, 552-553 Trichloroiodosilane, 466 Trichloromethylarenes, 119 Trichloro methyl)silane, 553 Trichlorosilane-Triethylamine, 553-544 Tricholomic acid, 188 Triethoxysilane, 554... 

Monosodium glutamate (MSG) is the sodium salt of glutamic acid. The flavor-enhancing property is not limited to MSG. Similar taste properties are found in the L-forms of q-amino dicarboxylates with four to seven carbon atoms. The intensity of flavor is related to the chemical structure of these compounds. Other amino acids that have similar taste properties are the salts of ibotenic acid, tricholomic acid, and L-thean-ine. 

An isomeric cycloglutamate tricholomic acid found in certain mushrooms... 

The symptoms of intoxication seen after ingestion of this mushroom appear 1 h after ingestion. Ibotenic acid is converted to muscimol by decarboxylation. Ibotenic acid and muscimol can both be detected unchanged in the urine. Other metabolites found in the urine include pantherin, tricholomic acid, and solitaric acid. Intoxication with this mushroom peaks at 5 h after ingestion and lasts for up to 10 h with a hangover effect the next day. 

Substances related to MSG and purine 5 -ribonucleotides include peptides, amino acids (e.g. cysteine, homocysteine, cysteine S-sulfonic acid, aspartic acid, a-amino adipic acid, a-methyl glutamic acid, tricholomic acid, ibotenic acid), pyrrolidone carboxylic acid, 3-methyl thiopropyl amine, and others [2, 10], They are of less commercial interest than MSG, IMP, and GMP. Chemical structures of some of these substances are depicted in Fig. 3.53. Relative umami effects of some are shown in Tab. 3.49. Tricholomic acid and ibotenic acid have been found in the mushrooms Tricholoma muscarium and Amanita stroboliformis, respectively. 

Dihydro-ibotenic acid or tricholomic acid (see Table 6) has been isolated from Tricholoma... 

The synthesis of tricholomic acid (751), an unusual amino acid isolated from tricholoma muscarium, uses an aldol condensation between 590 and 745 (a glycine acyl anion equivalent) to establish the absolute configuration of the amino functionality early in the synthesis (Scheme 108) [140]. The aldol reaction produces a 3 2 mixture of diastereomers that can be separated as in the form of the corresponding N-Cbz benzyl esters 746 and 747. 

In the mid-1960s investigations carried out independently by four research groups led to the isolation and subsequent structure elucidation from Amanita muscaria, A. strobiliformis, and A. pantherina of three fly-killing and narcosis potentiating compounds muscimol 37-40), ibotenic acid 40-44), and muscazone 43-47). At the same time tricholomic acid, another insecticidal constituent, was found in Tricholoma musca-rium 48,49). The nomenclature commonly accepted for these alkaloids was proposed by Eugster and Takemoto 50). 

There is a close structural affinity between ibotenic acid and its dihydro derivative, tricholomic acid (mp 207°C). Nevertheless the chemical interrelation between these compounds appeared to be difficult to prove because of the reactivity of the N—O bond which undergoes hydrogenolysis on mild catalytic hydrogenation of ibotenic acid (Scheme 13). The a-amino ketone formed in this way undergoes decarboxylation, dimerization, and reduction, becoming a trans derivative of piperazine 48). Tricholomic acid and its threo isomer have been synthesized from erythro- and f/ireo-diethyl D,L-3-hydroxyglutamate, respectively, by Iwasaki et al. 49). 

Alkaloids derived from glutamic acid, other than y-aminobutyric acid (GABA), include kainic acid isolated from Digenea simplex, domoic acid isolated from Chondria armata, acromelic acids isolated from Clitocybe acromelalga, ibotenic acid isolated from Amanita strobiliformis Amanita pantherina), and tricholomic acid isolated from Tricholoma musucaria, and are described in this chapter. 

In theTohoku area (northeast area of Honshu island) in Japan, there was a custom in which grilled Tricholoma muscarium (Tricholomataceae) was used for the purpose of killing flies. Takemoto et al. conducted research to isolate the active component(s) of this mushroom, and they succeeded in isolating an active component named tricholomic acid and elucidated its chemical structure [10].The active component was identified as a dihydro derivative of ibotenic acid, and it possessed powerfiil fly-killing activity... 

In addition, it was shown by Takemoto and Nakajima [11] that tricholomic acid and ibotenic acid possess peculiar palatability. In the meantime, it was established that kainic acid and domoic acid, which possess similar chemical structures, also showed fly-killing activity (see earlier Section 6.2). 

Ibotenic acid a-amino-3-hydroxy-5-isoxazole-acetic acid, M, 158, m.p. 145 C (d.), a psychotropic, weakly insecticidal substance. I. a. and its decarboxylation product, Muscimol (see), are amanita toxins. I. a. is found only in a few species of Amanita (fly agaric), at concentrations averaging 0.05 % of the fresh weight. It is pharmacologically very active, but less so than muscimol in most tests. Another La. derivative is Tricholomic acid (see). 

Tricholomic acid erytAro-dihydroibotenic acid, a compound isolated from the Basidiomycete Tricholo-ma muscarium. It can also be prepared by reduction of ibotenic acid. It possesses flavor promoting activity similar to, but much more active than, that of sodium glutamate. It also has a synergistic effect on the flavor improving property of inosinic acid and guanosine S -phosphate. 

Takemoto, T. and T. Nakajima, Structure of tricholomic acid, J. Pharm. Soc. Japan (Yakugaku Zasshi), 84, p. 1230, 1964b. 

Ibotenic acid is a likely carcinogen. In humans, poisoning is manifested by hallucinations. Ibotenic and tricholomic acids exhibit taste properties similar to those of monosodium glutamate (umami taste, see Section 8.3), but much more intense. Muscimol has similar effects as y-aminobutyric acid (GABA or 4-aminobutanoic acid), which acts as an inhibitory neurotransmitter of the central nervous system. 

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