Lipoic acid synthesis

The sulfur insertion into the C-6H bond occurs with inversion of stereochemistry [ 149]. Cysteine is the sulfur source [150]. Lipoic acid synthesis in a defined cell free system has not yet been accomplished. 

The aim of the present experiment was to study the PDHc activity in the livers and brains of developing rats born to females kept on a fat-free diet from 10 days after mating. The question arises in the mechanism of action of the supplemental linoleic acid given to the progeny after weaning on PDHc activity. Any effect could obviously be either direct, due to variation in the PDHc environment, or could be secondary and due to the stimulation of lipoic acid synthesis needed for further activation of the lipoyl transacetylase and lipoamide dehydrogenase. ... 

Although a variety of oxidizing agents are available for this transformation it occurs so readily that thiols are slowly converted to disulfides by the oxygen m the air Dithiols give cyclic disulfides by intramolecular sulfur-sulfur bond formation An example of a cyclic disulfide is the coenzyme a lipoic acid The last step m the laboratory synthesis of a lipoic acid IS an iron(III) catalyzed oxidation of the dithiol shown... 

Both chiral lactones and ketones have been utilized in asymmetric synthesis of bioactive compounds like lipoic acid [175[ and natural products like various insect pheromones [176[. 

Group-transfer reactions often involve vitamins3, which humans need to have in then-diet, since we are incapable of realizing their synthesis. These include nicotinamide (derived from the vitamin nicotinic acid) and riboflavin (vitamin B2) derivatives, required for electron transfer reactions, biotin for the transfer of C02, pantothenate for acyl group transfer, thiamine (vitamin as thiamine pyrophosphate) for transfer of aldehyde groups and folic acid (as tetrahydrofolate) for exchange of one-carbon fragments. Lipoic acid (not a vitamin) is both an acyl and an electron carrier. In addition, vitamins such as pyridoxine (vitamin B6, as pyridoxal phosphate), vitamin B12 and vitamin C (ascorbic acid) participate as cofactors in an important number of metabolic reactions. 

The Thil gene, which encodes aother sulfurtransferase protein, is also needed.3743 The enzymology of the insertion of this sulfur into the thiazole is uncertain but may resemble that involved in synthesis of biotin, lipoic acid, and molybdopterin.374 Linkage of the two parts of the thiamin molecule (step d, Fig. 25-21) is catalyzed by thiamin phosphate synthase, evidently via an SN2 type reaction.377-37713... 

Alfa Lipoic Acid Without writing an ad for anybody, let me simply say that Lipoic Acid increases receptor site sensitivity while also mimicking Insulin s actions. Though my choice for micro-nutrient of the year award for maximum creatine transport without an increase in bodyfat synthesis would be 4-hydroxy- Isoleucine. Major potential here ... 

Combination of microbiological chemistry, often yielding scaffolds not easily obtained by purely chemical means, and combinatorial chemistry, enabling rapid and efficient synthesis of analogs, provides a valuable tool for generation of novel test compounds. As an example [24] we describe here the application of our lipoic acid-derived thioketal linker [25] to the solid-phase synthesis of A4-3-keto steroidal ureas from / -sitosterol. 

Scheme 3.3.1. Scaffold synthesis from regrowing starting material. Reagents and conditions (a) Mycobacterium sp. (b) H2, (PPha) RhCI (c) 1. (+)- -lipoic acid methyl ester, NaBH4, MeOH, r.t., 2 h, then aqueous...

Some authors claim that liposaccharides can depress the content of TNF-a and increase the activity of superoxide dismutase (SOD) and catalase, thus—via mediators—they can affect the immune system (Can et al. 2003). It has been demonstrated that the NF-p transcription factor, (highly sensitive to the redox potential in its environment), which regulates synthesis of many mediators—cytokines, associated with inflammatory condition and the phenomenon of adhesion of cells— becomes deregulated in old age. Defense functions in such cases (and primarily in arthritis and arthritis-related conditions) are said to be performed by antioxidants (including a-lipoic acid), which can modulate the activity of monocytes and inhibit changes caused by deregulating of the transcription factor NF-kB under the influence of redox conditions in elderly people (Lee and Hughes 2002). 

Numerous linkers have been developed with the aim of immobilizing substrates on a solid support. Commercially available (+)-a-lipoic acid has been employed as a novel, chemically stable linker for the immobilization of ketones. The utility of this thioacetal-based linker in solid-phase synthesis has been demonstrated by the synthesis of several 4-acetylbiphenyls by means of the Suzuki reaction. The products were readily cleaved from the solid support by treatment with [bis(trifluoroacetoxy)iodo]benzene [PhI(OCOCF3)2] [107]. 

The method has also recently been used in a short synthesis of lipoic acid (Scheme and featured in MacMillan s conversion (equation 12a) of gibberellin As (23) into gibberellins As (24) and Ass (25), and in Mander s conversion of gibberellin A (26) into antheridic acid (equation 12b). In these last two examples the terminally disubstituted alkenes were oxidized widi almost complete stereoselectivity to give the IS-hydroxy pr ucts consistent widi sterically controlled tqrproach of the reagent The trisub-stituted double bond in equation (12b) was unaffected, as was the remaining fimctionidity in bodi substrate molecules. 

A synthesis of a-lipoic acid and derivatives has been reported. The pendant alkene of complex (111) was transformed to a primary alcohol (112) via hydroboration-oxidation sequence. Mitsunobu coupling of (112) with thiobenzoic acids to give (113), followed by desilylation and nucleophilic substitution again employing thiobenzoic acid gave the advanced intermediate (114) (Scheme 169). 

A preparatively useful synthesis of (R)-lipoic acid involves Baeyer-Villiger monooxygenase-catalyzed biotransformation of 2-(2-acetoxyethyl)cyclohexanone 351 to the key precursor, that is, chiral lactone 352 (Scheme 68) < 1997BMCL253, 1995CC1563>. The enzyme-catalyzed lactone 352 was then converted by a standard reaction procedure into the desired acid on enantioselective esterification of racemic lipoic acid, using C. rugosa lipase. 

Some acetogenic bacteria, which convert CO2 to acetic acid, form pyruvate for synthesis of carbohydrates, etc., by formation of formaldehyde and conversion of the latter to glycine by reversal of the PLP and lipoic acid-dependent glycine decarboxylase, a 4-protein system. The glycine is then converted to serine, pyruvate, oxaloacetate, etc. Propose a detailed pathway for this sequence. 

The metabolic functions of pantothenic acid in human biochemistry are mediated through the synthesis of CoA. Pantothenic acid is a structural component of CoA. which is necessary for many important metabolic processes. Pantothenic acid is incorporated into CoA by a. series of five enzyme-catalyzed reactions. CoA is involved in the activation of fatty acids before oxidation, which requires ATP to form the respective fatty ocyl-CoA derivatives. Pantothenic acid aI.so participates in fatty acid oxidation in the final step, forming acetyl-CoA. Acetyl-CoA is also formed from pyruvate decarboxylation, in which CoA participates with thiamine pyrophosphate and lipoic acid, two other important coenzymes. Thiamine pyrophosphate is the actual decarboxylating coenzyme that functions with lipoic acid to form acetyidihydrolipoic acid from pyruvate decarboxylation. CoA then accepts the acetyl group from acetyidihydrolipoic acid to form acetyl-CoA. Acetyl-CoA is an acetyl donor in many processes and is the precursor in important biosyntheses (e.g.. those of fatty acids, steroids, porphyrins, and acetylcholine). 

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