Efficient Preparation of Chiral Diamines via Red‐Al Reduction of N‐Boc‐Protected Amino Acid‐Derived Secondary Amides.

Voight, Eric A.; Bodenstein, Matthew S.; Ikemoto, Norihiro; Kress, Michael H.

doi:10.1002/chin.200626164

Cited by 2 publications

(3 citation statements)

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“…The unwanted side reaction, the reduction of the carbamate, has been reported with reductions using LiAlH 4 as reductant13, 14, in the literature, no such problems have been mentioned when using Red‐Al however10. It seems that the presence of aNCH 2 CH 2 OH moiety is beneficial for the selectivity of the reduction, in view of the fact that in the synthesis of 3 , 5 and 13, this side reaction was not observed.…”

Section: Resultsmentioning

confidence: 94%

“…The products 7 and 8 formed were reduced using sodium bis(2‐methoxyethoxy)aluminum hydride solution (Red‐Al), in lieu of borane. The rationale behind this method was based on a report by Voight et al 10, who reported the use of Red‐Al for the synthesis of N ‐Boc‐protected amino acid‐derived secondary amines. The chiral integrity of the Phaol moiety was not affected by this reduction, nor by the protection or deprotection steps.…”

Section: Resultsmentioning

confidence: 99%

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Synthesis of the orthogonally protected amino alcohol Phaol and analogs

Nelissen

Nuyts

Dehaen

et al. 2011

Journal of Peptide Science

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The development of a multigram synthesis of the orthogonally protected amino acid-derived Phaol [2-{[(2S)-2-amino-3-phenylpropyl]amino}ethanol] is described. The goal of this work is to synthesize an orthogonally protected Phaol in a multigram scale up to 10 g (Cbz-Phaol), so it can be used in solution-based peptide synthesis of peptaibols. Two synthetic schemes were proposed and examined. Between the reduction-coupling and the coupling-reduction scheme, the latter gave the best results. A two-step synthesis affords easily purifiable products. Several analogs were synthesized using this methodology. All the molecules were orthogonally protected, so that they can be used in peptide synthesis. Deprotection posed no problems.

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Section: Resultsmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Synthesis of the orthogonally protected amino alcohol Phaol and analogs

Nelissen

Nuyts

Dehaen

et al. 2011

Journal of Peptide Science

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“…This approach has been employed less frequently, probably because of the lack of selectivity that the hydride reagents have for various functionalities. 26 For the synthesis of 7, we tried the direct reduction method using various conditions (Table 1). LAH, alane, and borane were used as hydride-donor reducing agents.…”

Section: Chemistrymentioning

confidence: 99%

Structure-Based Design and Synthesis ofN^ω-Nitro-l-Arginine-Containing Peptidomimetics as Selective Inhibitors of Neuronal Nitric Oxide Synthase. Displacement of the Heme Structural Water

Seo

Igarashi

et al. 2007

J. Med. Chem.

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The neuronal isoform of nitric oxide synthase (nNOS), the enzyme responsible for the production of nitric oxide in the central nervous system, represents an attractive target for the treatment of various neurodegenerative disorders. X-ray crystal structures of complexes of nNOS with two nNOSselective inhibitors, (4S)-N-{4-amino-5-[(2-aminoethylamino]pentyl}-N′-nitroguanidine (1) and 4-N-(N ω -nitro-L-argininyl)-trans-4-amino-L-proline amide (2), led to the discovery of a conserved structural water molecule that was hydrogen bonded between the two heme propionates and the inhibitors (Figure 2). Based on this observation, we hypothesized that by attaching a hydrogen bond donor group to the amide nitrogen of 2 or to the secondary amine nitrogen of 1, the inhibitor molecules could displace the structural water molecule and obtain a direct interaction with the heme cofactor. To test this hypothesis, peptidomimetic analogues 3-5, which have either an N-hydroxyl (3 and 5) or N-amino (4) donor group, were designed and synthesized. X-ray crystal structures of nNOS with inhibitors 3 and 5 bound verified that the N-hydroxyl group had, indeed, displaced the structural water molecule and provided a direct interaction with the heme propionate moiety (Figures 4 and 5). Surprisingly, in vitro activity assay results indicated that the addition of a hydroxyl group (3) only increased the potency slightly against the neuronal isoform over the parent compound (1). Rationalizations for the small increase in potency are consistent with other changes in the crystal structures.

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Efficient Preparation of Chiral Diamines via Red‐Al Reduction of N‐Boc‐Protected Amino Acid‐Derived Secondary Amides.

Abstract: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Cited by 2 publications

References 1 publication

Synthesis of the orthogonally protected amino alcohol Phaol and analogs

Synthesis of the orthogonally protected amino alcohol Phaol and analogs

Structure-Based Design and Synthesis ofN^ω-Nitro-l-Arginine-Containing Peptidomimetics as Selective Inhibitors of Neuronal Nitric Oxide Synthase. Displacement of the Heme Structural Water

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Efficient Preparation of Chiral Diamines via Red‐Al Reduction of N‐Boc‐Protected Amino Acid‐Derived Secondary Amides.

Abstract: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Cited by 2 publications

References 1 publication

Synthesis of the orthogonally protected amino alcohol Phaol and analogs

Synthesis of the orthogonally protected amino alcohol Phaol and analogs

Structure-Based Design and Synthesis ofNω-Nitro-l-Arginine-Containing Peptidomimetics as Selective Inhibitors of Neuronal Nitric Oxide Synthase. Displacement of the Heme Structural Water

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Structure-Based Design and Synthesis ofN^ω-Nitro-l-Arginine-Containing Peptidomimetics as Selective Inhibitors of Neuronal Nitric Oxide Synthase. Displacement of the Heme Structural Water