Synthesis of 2-acetyl-4-(1,2,3,4-tetrahydroxybutyl)imidazole

Sweeny, James G.; Ricks, Edith E.; Estrada-Valdes, Maria C.; Iacobucci, Guillermo A.; Long, Robert C.

doi:10.1021/jo00207a048

Cited by 16 publications

(9 citation statements)

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“…The physical properties of our synthetic 1 (mp 240−244 °C (lit . mp 234−236 °C), [α] 23 D −14.9° ( c 1.4, HCl/H 2 O) (lit .…”

Section: Resultsmentioning

confidence: 99%

“…To investigate the structure−activity relationships of this structurally simple but biologically intriguing molecule, we desired a general and flexible synthesis of THI analogues. Three earlier syntheses of THI have been reported, and these all rely on the use of glucose derivatives to prepare the 1,2,3,4-tetrahydroxybutyl side chain. − These syntheses are not sufficiently flexible for the synthesis of the stereoisomers of THI. In a recent communication, we reported a new synthetic protocol for the synthesis of THI.…”

Section: Introductionmentioning

confidence: 99%

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Asymmetric Synthesis of 2-Acetyl-4(5)-(1,2,3,4-tetrahydroxybutyl)imidazoles

and

Pyne

1997

J. Org. Chem.

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A method for preparing the eight stereoisomers of the biologically active compound (1R,2S,3R)-2-acetyl-4(5)-(1,2,3,4-tetrahydroxybutyl)imidazole (THI, 1) is reported. This method employs a palladium(0)-catalyzed coupling of 1-(ethoxymethyl)-4-iodoimidazole (7) to functionalized vinylstannanes (R)- or (S)-12a,b or 13a,b or 1-alkynylstannanes (R)- or (S)-6a,b to introduce the C-4 imidazole four-carbon side chain. The 1,2-dihydroxy functionality of the butyl side chain was introduced by Sharpless catalytic asymmetric dihydroxylation reactions.

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“…The physical properties of our synthetic 1 (mp 240−244 °C (lit . mp 234−236 °C), [α] 23 D −14.9° ( c 1.4, HCl/H 2 O) (lit .…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Asymmetric Synthesis of 2-Acetyl-4(5)-(1,2,3,4-tetrahydroxybutyl)imidazoles

and

Pyne

1997

J. Org. Chem.

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“…The effect of AC is evident after 2-3 days of dosage, and after withdrawal of AC lymphocyte counts return within days to baseline levels; the effects of AC on lymphocyte subpopulations have not hitherto been ascertained. Pyridoxine deficiency of the diet was shown to augment the lymphopenia-inducing capacity of AC, and the component of AC which caused lymphopenia in rats was identified as THI (5)(6)(7)(8). In rats, the effects of THI may be transient and, at dose levels that have only marginal effects on lymphocytes, the animals may develop a tolerance (C. Chappel, pers.…”

Section: Discussionmentioning

confidence: 99%

“…Deficiency of pyridoxine (Vitamin B6) in the diet was shown to augment the lymphopeniainducing capacity of AC (4). The component of AC which causes lymphopenia in the rat is 2-acetyi-4(5)-tetrahydroxybutylimidazole (THI) (5)(6)(7)(8). The aim of the present study was to ascertain whether THI induced lymphopenia in mice as it does in rats and, if so, the doses required to induce this effect.…”

Section: Introductionmentioning

confidence: 99%

Lymphopenic effects on mice of a component of ammonia caramel, 2‐acetyl‐4(5)‐tetrahydroxybutylimidazole (THI)

1988

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Summary A derivative of ammonia caramel colour (AC) is known to induce a selective lymphopenia in rats. Accordingly, the haematological effects were studied in mice of oral administration in drinking water of 2-acetyl-4(5)-tetrahydroxybutylimidazole (THI), the component of AC responsible for lymphopenia. Initially five groups of BALB/c mice (five mice per group) were given doses of THI ranging from 0 to 200 parts/10^ and bled weekly. Doses of THI from 5 to 100 parts/10^ had no effect on circulating leucocytes over 6 weeks, but lymphopenia occurred with 200 parts/10^. An increase in the concentration of T"HI to 400 parts/10^ in the group on the lowest dose resulted in lymphopenia. An increase indosagein two groups of mice, to 1000 and 2000 parts/10^. resulted in marked lymphopenia. The number of neutrophils. eosinophils and monocytes remained unchanged throughout the experiment. Measurement of the proportions of CD4(L3T4)"'" and CD8(Ly2)"^ lymphocytes in lymph nodes from mice on high doses of THI did not show a selective depression of either subset, although both were increased relative to non-T cells. THI causes a selective lymphopenia in mice, as in rats, but at relatively higher doses, and merits investigation in mice as an experimental treatment for states of lymphocyte excess or overactivity.

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“…An example of carbohydrate based bioactive imidazoles is the 2-acetyl-4-tetrahydroxy-butyl imidazole 1 which has been found as a Maillard product caramel color 31 in e.g. roasted coffee 32 and is synthetically accessible from D-glucosone, 33 D-Glucoseamine 34 or 1-amino-1-deoxy-D-fructose. 35 The imidazole 1 is highly interesting due to its pharmacological properties as a potent sphingosin-1-phospahate lyase inhibitor making it herewith commercially valuable in the treatment of autoimmune diseases 36 and rheumatoid arthritis.…”

Section: Introductionmentioning

confidence: 99%