Thiamine vitamin activity

The thiazole ring can be found in numerous molecules that possess biological activity the thiamine (vitamin B,), penicillins, antiinflamatory and bactericidals compounds, and so forth. 

Naturally occurring quaternary ammonium compounds have been reviewed (179). Many types of aliphatic, heterocycHc, and aromatic derived quaternary ammonium compounds are produced both in plants and invertebrates. Examples include thiamine (vitamin B ) (4) (see Vitamins) choline (qv) [62-49-7] (5) and acetylcholine (6). These have numerous biochemical functions. Several quaternaries are precursors for active metaboUtes. 

Lipid soluble analogs of thiamine (vitamin Bj) 1126 have a number of therapeutic uses, and examples are acetiamine 1127 (R = Me), bentiamine 1127 (R = Ph), fursultiamine 1128, and octotiamine 1129 which has antiinflammatory activity. 

Thiamin 0.23 mg or more per 1000 kcal of food consumed and a minimum total of 0.8 mg/day. Replacement of the methyl group on the pyrimidine ring by ethyl, propyl, or isopropyl gives compounds with some vitamin activity, but replacement by hydrogen cuts activity to 5% of the original. The butyl analog is a competitive inhibitor. 

THIAMINE (Vitamin Bi). Some earlier designations for this substance included aneurin, antmeuntic factor, antibenben factor, and oryzamin. Thiamine is metabolically active as thiamine pyrophosphate (TPP). the formula of which is ... 

Acetals result from oxidative coupling of alcohols with electron-poor terminal olefins followed by a second, redox-neutral addition of alcohol [11-13]. Acrylonitrile (41) is converted to 3,3-dimethoxypropionitrile (42), an intermediate in the industrial synthesis of thiamin (vitamin Bl), by use of an alkyl nitrite oxidant [57]. A stereoselective acetalization was performed with methacrylates 43 to yield 44 with variable de [58]. Rare examples of intermolecular acetalization with nonactivated olefins are observed with chelating allyl and homoallyl amines and thioethers (45, give acetals 46) [46]. As opposed to intermolecular acetalizations, the intramolecular variety do not require activated olefins, but a suitable spatial relationship of hydroxy groups and the alkene[13]. Thus, Wacker oxidation of enediol 47 gave bicyclic acetal 48 as a precursor of a fluorinated analogue of the pheromone fron-talin[59]. 

When, in 1832, Wohler and Liebig first discovered the cyanide-catalyzed coupling of benzaldehyde that became known as the benzoin condensation , they laid the foundations for a wide field of growing organic chemistry [1]. In 1903, Lapworth proposed a mechanistical model with an intermediate carbanion formed in a hydrogen cyanide addition to the benzaldehyde substrate and subsequent deprotonation [2]. In the intermediate active aldehyde , the former carbonyl carbon atom exhibits an inverted, nucleophilic reactivity, which exemplifies the Umpo-lung concept of Seebach [3]. In 1943, Ukai et al. reported that thiazolium salts also surprisingly catalyze the benzoin condensation [4], an observation which attracted even more attention when Mizuhara et al. found, in 1954, that the thiazolium unit of the coenzyme thiamine (vitamin Bi) (1, Fig. 9.1) is essential for its activity in enzyme biocatalysis [5]. Subsequently, the biochemistry of thiamine-dependent enzymes has been extensively studied, and this has resulted in widespread applications of the enzymes as synthetic tools [6]. 

Referring to a mechanistic classification of organocatalysts (Seayad and List 2005), currently the two most prominent classes are Brpnsted acid catalysts and Lewis base catalysts. Within the latter class chiral secondary amines (enamine, iminium, dienamine activation for a short review please refer to List 2006) play an important role and can be considered as—by now—already widely extended mimetics of type I aldolases, whereas acylation catalysts, for example, refer to hydrolases or peptidases (Spivey and McDaid 2007). Thiamine-dependent enzymes, a versatile class of C-C bond forming and destructing biocatalysts (Pohl et al. 2002) with their common catalytically active coenzyme thiamine (vitamin Bi), are understood to be the biomimetic roots ofcar-bene catalysis, a further class of nucleophilic, Lewis base catalysis with increasing importance in the last 5 years. 

Lappert developed the thermolysis of an electron-rich olefin in the presence of a transition metal complex as another way to synthesise these compounds [4], When, in 1975, Clarke and Taube published their findings on carbon coordinated purine transition metal complexes [5], transition metal NHC complexes with functionalised NHC made their debut in biochemistry. The chemistry of carbenes from natural products became firmly established following the discovery that the catalytic activity of thiamine (vitamin Bl) is based on the intermediate formation of a carbene derived from thiazole [6-9] (see Figure 1.2). 

The nonannulated parent compound thiazole has been implicated as the active centre of the naturally occurring enzyme thiamine (vitamin Bl) [1,2], It catalyses the decarbonyla-tion of pyruvic acid to acetaldehyde and the benzoin condensation of aromatic aldehydes... 

Studies on thiamine (vitamin Bi) catalyzed formation of acyloins from aliphatic aldehydes and on thiamine or thiamine diphosphate catalyzed decarboxylation of pyruvate have established the mechanism for the catalytic activity of 1,3-thiazolium salts in carbonyl condensation reactions. In the presence of bases, quaternary thiazolium salts are transformed into the ylide structure (2), the ylide being able to exert a cat ytic effect resembling that of the cyanide ion in the benzoin condensation (Scheme 2). Like cyanide, the zwitterion (2), formed by the reaction of thiazolium salts with base, is nucleophilic and reacts at the carbonyl group of aldehy s. The resultant intermediate can undergo base-catalyzed proton... 

The thiamin (vitamin Bl) molecule contains a quaternary ammonium functionality and is thus badly absorbed. In healthy patients the necessary amounts of thiamin are absorbed, thanks to an active transport mechanism coupled with ATP consumption. However, these mechanisms are rapidly saturable and easily inhibited, especially by... 

D. This patient has exhibited symptoms of beri beri heart disease, which is a result of a nutritional deficiency in vitamin Bj (thiamine). The active form of the vitamin, thiamine pyrophosphate, is a required cofactor for a-ketoglutarate dehydrogenase. 

Thiamine Vitamin Bp a water-soluble vitamin containing a thiazolium ring. The active form of the vitamin is thiamine pyrophosphate, which is an important coenzyme for many biochemical reactions. 

Thiamine (vitamin Bj) is an important water-soluble vitamin that, in its active form of thiamine pyrophosphate, is used as a cofactor in enzymatic reactions that involve the transfer of an aldehyde group. Thiamine can be synthesized by plants and some microorganisms, but not usually by animals. Hence, humans must obtain thiamine from the diet, though small amounts may be obtained from synthesis by intestinal bacteria. Because of its importance in metabolic reactions, it is present in large amounts in skeletal muscle, heart, liver, kidney, and brain. Thus, it has a widespread distribution in foods, but there can be a substantial loss of thiamine during cooking above 100°C (212°F). 

Figure 15-1. Activation of thiamine (vitamin Bj) to the active cofactor, thiamine pyrophosphate (TPP) by the enzyme TPP synthetase.

Thiamine (vitamin Bj) is an important water-soluble vitamin that, in its active form of thiamine pyrophosphate, is used as a cofactor in enzymatic reactions that involve the transfer of an aldehyde group. 

B3. B hidi, Z. G., Weight increase in the rat due to thiamine disulfide activation by ascorbic acid. Internat. Rev. Vitamin Research 80, 305-322 (1960). 

In order to study the nature of activated hydrogens in compounds related to thiamine (vitamin Bj), Hafferl, Lundin, and Ingraham273... 

Tliiamine (vitamin Bi) Thiamine pyropluwphate Activation and transfer of alddiydes 490... 

Thiamin is also reactive to the primary water radicals and, possibly to protein radicals, resulting in its conversion to product or products without vitamin activity. As Figure 1 shows, the loss of thiamin in pork decreases substantially... 

The thiamin (vitamin BO molecule contains a quaternary ammonium functionality and is thus badly absorbed. In healthy patients the necessary amounts of thiamin are absorbed thanks to an active transport mechanism coupled with ATP consumption. However, these mechanisms are rapidly saturable and easily inhibited, especially by chronic alcoholic consumption. As a consequence of the insufficient absorption of thiamin, alcoholism often entails Wernicke s encephalopathy (neurological disorders such as nystagmus, ocular motor nerve paralysis, memory losses, disorientation). The design of lipophilic prodrugs, able to reach the CNS by passive diffusion was then undertaken compounds like (a) and (b) result from lipophilic disulphide derivation of the open ring thiolate anion corresponding to thiamine (Fig. 33.39). 

Only oxazole, of the trio, does not play any part in normal biochemical processes, though there are secondary metabolites (especially from marine organisms) which incorporate thiazole (and oxazole) units - the antibiotic cystothiazole A, from the myxobacterium Cyctobacter fuscus is an example. Imidazole occurs in the essential amino acid histidine histidines within enzymes are intimately involved in catalysis requiring proton transfers. The structurally related hormone, histamine, is a vasodilator and a major factor in allergic reactions such as hay fever. The thiazolium ring is the chemically active centre in the coenzyme derived from thiamin (vitamin B,). 

Benfotiamine, a lipid-soluble thiamine (vitamin Bl) derivative, prevents the increase in the intracellular hexosamine pathway and polyol pathway activation during hyperglycaemia [53]. It decreases hyperglycaemia-induced intracellular AGE formation... 

Thiazine containing alkaloids are relatively rare in Nature, but they range in structural complexity from simple monocyclic derivatives such as chondrine and benzothiazines such as the aplidinones, to more complex tri- and polycyclic compounds exemplified by ansafhiazin and the shermilamines. On the other hand, the simplest N,S-heterocycle - the 5-membered thiazole - is relatively common in Nature, and, for example, plays a vital role in the function of thiamine (vitamin Bi). Thiazole rings also occur in important biologically active natural products such as the epothilones (Figure 1). 

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