Reductive animation

Reductive animations also occur in various biological pathways, fn the biosynthesis of the amino acid proline, for instance, glutamate 5-semjaldehyde undergoes internal imine formation to give 1-pyrrolinium 5-carboxylate, which is then reduced by nucleophilic addition of hydride ion to the C=N bond. 

How might you prepare, f-methyl-2-phenylethylamine using a reductive animation... 

Problem 24.11 How might the following amines be prepared using reductive animation reactions . Show all precursors if more than one is possible. 

How might a reductive animation be used to synthesize ephediine, an amino alcohol that is widely used for the treatment of bronchial asthma ... 

The first step in the biological degradation of lysine is reductive animation with a-ketoglutarate to give saccharopine. Nicotinamide adenine dinucleotide phosphate (NADPH), a relative of NADH, is the reducing agent. Show the mechanism. 

Reductive animation (Sections 24.6, 26.3) A method for preparing an amine by reaction of an aldehyde or ketone with ammonia and a reducing agent. 

Claisen rearrangement, 1194-1195 dehydration, 622 elimination reactions, 393 oxidation, 625-626 radical reactions, 243-244 characteristics of, 162-164 comparison with laboratory reactions, 162-164 conventions for writing, 162. 190 energy diagram of, 161 reduction, 723-725 reductive animation, 932 substitution reactions, 381-383 Biological reduction, NADH and, 610-611... 

Reductive animation, 930-932 amino acid synthesis and, 1026 biological example of, 932 mechanism of, 931 Refining (petroleum). 99-100 Regiospecific, 191... 

Two reactions for the production of L-phenylalanine that can be performed particularly well in an enzyme membrane reactor (EMR) are shown in reaction 5 and 6. The recently discovered enzyme phenylalanine dehydrogenase plays an important role. As can be seen, the reactions are coenzyme dependent and the production of L-phenylalanine is by reductive animation of phenylpyruvic add. Electrons can be transported from formic add to phenylpyruvic add so that two substrates have to be used formic add and an a-keto add phenylpyruvic add (reaction 5). Also electrons can be transported from an a-hydroxy add to form phenylpyruvic add which can be aminated so that only one substrate has to be used a-hydroxy acid phenyllactic acid (reaction 6). 

The end game was optimized, wherein diastereoselectivity of the reductive animation was further improved by using a more sterically bulky reducing reagent and by running the reaction at higher temperature. 

The drug candidate 1 was prepared from chiral cyclopentanol 10 as shown in Scheme 7.3. Reaction of 10 with racemic imidate 17, prepared from the corresponding racemic benzylic alcohol, in the presence of catalytic TfOH furnished a 1 1 mixture of diastereomers 18 and 19 which were only separated from one another by careful and tedious chromatography. Reduction of ester 18 with LiBH4 and subsequent Swern oxidation gave aldehyde 20 in 68% yield. Reductive animation of 20 with (R)-ethyl nipecotate L-tartrate salt 21 and NaBH(OAc)3 and subsequent saponification of the ester moiety yielded drug candidate 1. 

Scheme 2 Abbreviations DBU, 1,8-diazabicyclo[5.4.0]undec-7-ene DMA, N,/V-dimethylacetamide TBTU, O-benzotriazole-1 -yl-N,N,N, N -tetramethy-luronium tetrafluoroborate DIEA, diisopropylethylamine RA, reductive animation TFA, trifluoroacetic acid DCM, dichloromethane.

Hydrogenation of Nitrogen-Containing Multiple Bonds and Reductive Animation 71... 

Figure 14.9 Reaction scheme for production of (—)-ephedrine based on enzymatic C—C bond formation using Saccharomyces cerevisiae coupled with a chemical reductive animation...

Lemmtyinen and coworkers <01JPP835> have devised a protocol, in which the phytochlorin 37 containing a formyl group was transformed into glycine derivative 50 via reductive animation (Scheme 15). In the final step, derivative 50 was reacted with benzaldehyde and C6o, and gave rise to the phytochlorin C(,o diad 51. 

Another route to the formation of piperidine heterocycles is cyclization via reductive animation utilizing various hydride sources. The scheme below depicts a bis reductive animation, using sodium triacetoxyborohydride as the hydride source, to generate exo-178 and endo-179 azabicyclo[3.2.1]octane amino acids in moderate yields <06JOC8467>. 

Gheorghe et al. make use of sodium cyanoborohydride as a hydride source in the synthesis of 5-arylpiperidines <06OL1653>. Kellehar and Kelly report the formation of a spiro -lactam using sodium borohydride in the key reductive animation step <06TL3005>. 

Scheme 2. Double N-alkylation of a sugar aldehyde by reductive animation.65...

Zemplen O-deacetylation followed by cleavage of the acetal protecting groups with aqueous TFA afforded G(0) dendron 451, whose reducing end was reductively animated with bismethylamino trisaccharide 452 using cyanoborohydride in 1 1 MeOH-H20 to furnish the G(l) dendron 435 in 48% yield. 

M. Dubber and T. K. Lindhorst, Exploration of reductive animation for the synthesis of cluster glycosides, Synthesis, 2 (2001) 327-330. 

A. Nelson and J. F. Stoddart, Synthesis of lactoside glycodendrons using photoaddition and reductive animation methodologies, Carbohydr. Res., 339 (2004) 2069-2075. 

Coupling Glycoproteins to Amine-Dendrimers by Reductive Animation... 

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