Chiral polyamines from reduction of polypeptides: asymmetric pyridoxamine-mediated transaminations

Zhou, Wenjun; Yerkes, Nancy; Chruma, Jason J.; Liu, Lei; Breslow, Ronald

doi:10.1016/j.bmcl.2005.01.021

Cited by 28 publications

(18 citation statements)

References 17 publications

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“…We have seen that, with borane, such polypeptides can be converted to polyamines with no scrambling of the asymmetric centers and no cleavage of the chains. [17,18] This has been successful with quite long polypeptides. In some earlier work, we also showed that with even relatively small polypeptides we could convert a covalently linked peptide/pyridoxamine structure such as 9 into the corresponding amine derivative 10 and achieve interesting chiral selectivity in transaminations (Scheme 6).…”

Section: Chiral Polyamine Catalystsmentioning

confidence: 97%

“…In some earlier work, we also showed that with even relatively small polypeptides we could convert a covalently linked peptide/pyridoxamine structure such as 9 into the corresponding amine derivative 10 and achieve interesting chiral selectivity in transaminations (Scheme 6). [17] The product amines were quite good catalysts for transaminations, with enantioselectivity of up to 85 % ee, while the corresponding polypeptides from which these were derived gave less than 5 % enantioselectivity. Scheme 5.…”

Section: Chiral Polyamine Catalystsmentioning

confidence: 99%

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Water Exclusion and Enantioselectivity in Catalysis

et al. 2006

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Enzymes are large molecules. A number of arguments can be offered as to why this should be so, including the need for a large protein, consisting of a linear sequence of amino acids, to have a preferential folding into the biologically effective three-dimensional structure. There are also arguments that the dynamics of segment motion in a large protein can contribute to catalytic effectiveness. However, there is another argument for the large molecules characteristic of enzymes that is quite convincing-their size and structure let reactions occur inside a hydrophobic, nonaqueous, and nonpolar region of the protein while the outside of the protein has polar groups and is compatible with the aqueous solvents.Two interesting effects result from this. On the one hand, substrates that have hydrophobic groups will tend to bind in the nonpolar interior of the protein, where the catalytic groups can be located. On the other hand, water is in one respect an enemy of rate, even though the hydrophobic effect depends on water for its positive contribution to reaction rates. In a A C H T U N G T R E N N U N G reaction in which acid and base groups play a catalytic role, water that is hydrogen bonded to these groups must normally be removed before they can effectively act on the substrate. The energy cost of desolvation of these catalytic groups-and perhaps also desolvation of the substrates-can slow the reaction considerably. For this reason it has often been proposed that the interior of the protein, without any water molecules or highly polar groups in it, is a better place to perform a catalyzed reaction and that such a medium will increase the rates of the processes. Water Exclusion in Polymeric Enzyme MimicsIn order to explore this, we have synthesized a number of enzyme mimics based on polymers. [1][2][3][4][5][6][7] Our most extensive studies have been directed to branched polyethylenimines, a group of commercial polymers whose catalytic properties have been previously studied by Klotz, [8,9] by Suh, [9,10] and by Kirby.[11] They explored hydrolysis and cleavage reactions, while we have been interested in synthetic processes. In our first studies, [1][2][3][4][5] we examined the amination of keto acids by pyridoxamine units attached to the polymers. Later, we examined the even more effective system in which the pyridoxamine units were reversibly bound to the hydrophobic core of such a polymer, in imitation of the binding of coenzymes by the natural enzymes.[6]As we have described, we synthesized our transaminase mimics by using a variety of polyethylenimines. In the first system, we used a rather large polyethylenimine with a number-average molecular weight of about 60 000 and with high polydispersity; the weight-average molecular weight was 750 000.[1] This commercial polymer has about 1400 nitrogens; about 25 % of them are primary amino groups, 50 % are secondary amines, and 25 % are tertiary amines. We alkylated about 10 % of the nitrogens with alkyl halides ranging from methyl iodide up to dodecyl iodide, and then ...

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Section: Chiral Polyamine Catalystsmentioning

confidence: 97%

Section: Chiral Polyamine Catalystsmentioning

confidence: 99%

Water Exclusion and Enantioselectivity in Catalysis

et al. 2006

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“…Previous work in our group demonstrated that small peptides with up to three residues could be reduced to the corresponding chiral amines using borane complexed to THF 6. Other researchers have also demonstrated that the synthesis of polyamines via the reduction of polypeptides is possible,7 however, many of these methods require harsh conditions to break up the amine-borane complex 8…”

Section: Synthetic Strategy I - Synthesis Of Chiral Amines From the Rmentioning

confidence: 99%

Synthesis and catalytic properties of diverse chiral polyamines

Levine

Kenesky

Zheng

et al. 2008

Tetrahedron Letters

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Chiral polyamines can be utilized for a variety of potential applications, ranging from asymmetric catalysis to nonviral gene delivery systems for DNA and RNA. They can also be utilized to solubilize carbon nanotubes. Thus, methods for the straightforward synthesis of chiral polyamines are needed. We present herein two synthetic strategies for accessing chiral polyamines. The potential of these chiral amines to catalyze two organic reactions with a high degree of chiral induction was also explored. Text: Chiral polyamines have been utilized for a variety of applications. First, polyamines are polycationic at neutral pH; as such, they interact strongly with both DNA and RNA.1 They can therefore be utilized as effective nonviral gene delivery agents.2 Second, chiral polyamines are efficient catalysts for various organic transformations.3 Polyamines have also been used to solubilize carbon nanotubes.4 Finally, chiral polyamines are excellent ligands for many transition metals.5 Due to their numerous applications, high-yielding synthetic strategies for their preparation are in great demand. We present herein two synthetic strategies for accessing chiral polyamines, and the potential of these chiral amines to catalyze two organic reactions.

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“…2 We also saw enantioselective transamination with a pyridoxamine covalently attached to a chiral triamine that was derived by reduction of a tripeptide (but not with the unreduced tripeptide). 21 We then wished to create a polyamine catalyst that could produce enantioselective transamination by the simple action of the chirality of the polymer itself, as happens in natural enzymes.…”

Section: Introductionmentioning

confidence: 99%