Reductive amination biological example

Esters of diphenylacetic acids with derivatives of ethanol-amine show mainly the antispasmodic component of the atropine complex of biologic activities. As such they find use in treatment of the resolution of various spastic conditions such as, for example, gastrointestinal spasms. The prototype in this series, adiphenine (47), is obtained by treatment of diphenyl acetyl chloride with diethylaminoethanol. A somewhat more complex basic side chain is accessible by an interesting rearrangement. Reductive amination of furfural (42) results in reduction of the heterocyclic ring as well and formation of the aminomethyltetrahydro-furan (43). Treatment of this ether with hydrogen bromide in acetic acid leads to the hydroxypiperidine (45), possibly by the intermediacy of a carbonium ion such as 44. Acylation of the alcohol with diphenylacetyl chloride gives piperidolate (46). ... 

A laboratory synthesis that is patterned after a biological synthesis. For example, the synthesis of amino acids by reductive amination resembles the biosynthesis of glutamic acid. (p. 1164) Proteins that provide all the essential amino acids in about the right proportions for human nutrition. Examples include those in meat, fish, milk, and eggs. Incomplete proteins are severely deficient in one or more of the essential amino acids. Most plant proteins are incomplete, (p. 1160)... 

This method is particularly interesting because it is a close laboratoiy analogy of a pathway by which some amino acids are bio.synthesized in nature. For example, the major route for glutamic acid synthesis in most organisms is by reductive amination of or-ketoglutaric acid. The biological... 

A typical second step after the insertion of CO into aryl or alkenyl-Pd(II) compounds is the addition to alkenes [148]. However, allenes can also be used (as shown in the following examples) where a it-allyl-r 3-Pd-complex is formed as an intermediate which undergoes a nucleophilic substitution. Thus, Alper and coworkers [148], as well as Grigg and coworkers [149], described a Pd-catalyzed transformation of o-iodophenols and o-iodoanilines with allenes in the presence of CO. Reaction of 6/1-310 or 6/1-311 with 6/1-312 in the presence of Pd° under a CO atmosphere (1 atm) led to the chromanones 6/1-314 and quinolones 6/1-315, respectively, via the Jt-allyl-r 3-Pd-complex 6/1-313 (Scheme 6/1.82). The enones obtained can be transformed by a Michael addition with amines, followed by reduction to give y-amino alcohols. Quinolones and chromanones are of interest due to their pronounced biological activity as antibacterials [150], antifungals [151] and neurotrophic factors [152]. 

To make use of the Mannich reaction it is possible to methylate the N-atom of the new side chain and eliminate trimethylamine. The product, a 3-methyleneindoleninium salt, can then be trapped with suitable nucleophiles. In the example shown in Scheme 7.7b, cyanide ion is used, and reduction of the resultant nitrile yields the important amine trypta-mine. Indol-3-ylacetonitrile is also the source of indol-3-ylacetic acid and other biologically useful compounds (see Section 7.1.7). 

A 2-amino group in chroman is more labile than its isomers and is hydrolyzed to the alcohol by acids for example both the amines (699) and (700) give the corresponding alcohols by treatment with nitrous acid and 50% hydrochloric acid, respectively. 6-Amino-chromans are of interest because of their chemical and biological resemblance to the tocopherols. The tocopheramines (701 R1, R2, R3 = H or Me) show antioxidant and other properties of the corresponding phenols and are no more toxic. They may be obtained by catalytic or chemical reduction of the nitrochromans (81HC(36)189). 

The different biological effects of NO and HNO are a function of distinct molecular targets for these redox siblings. For example, NO preferentially reacts with reduced metals to directly form a nitrosyl complex (Eq. 13). The identical product is formed by reductive nitrosylation of HNO toward oxidized metals (Eq. 12). Exceptions of course exist (e.g., the reverse of Eq. 19). Perhaps more importantly, HNO reacts with thiols (Eq. 21) and amines (Eq. 25) directly while NO must interact with these species indirectly, following oxidation to a nitrosating or oxidizing agent (36). 

Recently, the arylation of several specific primary amines have been studied because of the potential biological relevance of the products or products further downstream in a synthetic sequence. For example, cyclopropylamine was shown to be a viable substrate for the coupling under standard conditions [203]. Reactions of 7-azabicyclo[2.2.1]heptane have also been conducted [204] under relatively standard conditions, but with bis(imidazol-2-ylidene) as ligand. Complexes of this ligand and DPPF showed similar catalytic activities, which proved to be superior to those of most bis(phosphine)s. ortfio-Halo anilines were also studied, in this case to provide access to carbolines after use of the halogen as a means of effecting cycliza-tions by an electrophilic or reductive C-C bond formation with the other N-aryl group [205]. 

The Staudinger reduction has found its way into the synthesis of many biologically relevant molecules in both academia and industry. The following example, published in 2004 from scientists at Abbott Laboratories, comes from their work toward synthesizing new famesyltransferase inhibitors. Quinolone 62 is one example from this publication.29 In the synthesis of this particular inhibitor, bromide 59 was reacted with sodium azide to afford the corresponding azide in 70% yield. Addition of an excess of triphenylphosphine to compound 60 in refluxing THF/H2O delivered the desired amine 61 in 83% yield. Reductive animation then afforded the final target compound 62. 

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