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:10.1016/j.tetlet.2006.01.056

Cited by 17 publications

(5 citation statements)

References 21 publications

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“…A third way to synthesize secondary amines is by a direct reduction of an amide to an amine. This approach has been employed less frequently, probably because of the lack of selectivity that the hydride reagents have for various functionalities . For the synthesis of 7 , we tried the direct reduction method using various conditions (Table ).…”

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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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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“…40 The most commonly applied method for the reduction of amides to give primary, secondary, or tertiary amines is reduction with aluminum hydrides. The most important reagents are lithium aluminum hydride, [178,179] sodium aluminum hydride, [89] lithium aluminum hydride/aluminum trichloride, [180] lithium trimethoxyaluminum hydride, [90,99,181] sodium bis(2-methoxyethoxy)aluminum hydride (Red-Al), [182][183][184][185] and diisobutylaluminum hydride (DIBAL-H). [186] They are used in inert solvents, such as diethyl ether, tetrahydrofuran, or toluene.…”

Section: Scheme 19 Synthesis Of A-substituted Primary Amines By Additmentioning

confidence: 99%

Synthesis by Reduction

Enders¹,

Schaumann²

2009

Category 5, Compounds With One Saturated Carbon Heteroatom Bond

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“…3 Some less conventional uses involve the cleavage of benzyl ethers of vicinal methoxy-containing compounds. 4 Abstracts Figure 1 O (F) Voight et al 11 used Red-Al ® for the efficient preparation of chiral diamines via selective reduction of N-Boc-protected amino acid derived secondary amides. The reactions proceeded with minimal overreduction or cyclic urea formation.…”

Section: Introductionmentioning

confidence: 99%

Sodium Bis(methoxyethoxy)aluminium Hydride

Rathi¹

2010

Synlett

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This feature focuses on a reagent chosen by a postgraduate, highlighting the uses and preparation of the reagent in current research Sodium Bis(methoxyethoxy)aluminium HydrideCompiled by Akshat Rathi Akshat Rathi was born in Nashik, Maharashtra, India in 1987. He received his B.Tech. in Pharmaceutical Chemistry & Technology from the Institute of Chemical Technology (formerly UDCT), Mumbai. During his undergraduate degree, he was a research associate under Prof. S. D. Samant at Mumbai and also a visiting scholar at the University of Sheffield under the supervision of Prof. Iain Coldham. His undergraduate thesis, under Prof. M. S. Degani, involved work on the synthesis of novel systemic biological markers. At present, he is working towards his M.Sc. by Research in Organic Chemistry at the University of Oxford, under the tutelage of Prof. T. J. Donohoe. His current research project involves studies towards the synthesis of microsclerodermin F.

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Efficient preparation of chiral diamines via Red-Al reduction of N-Boc-protected amino acid-derived secondary amides

Cited by 17 publications

References 21 publications

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

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

Synthesis by Reduction

Sodium Bis(methoxyethoxy)aluminium Hydride

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Efficient preparation of chiral diamines via Red-Al reduction of N-Boc-protected amino acid-derived secondary amides

Cited by 17 publications

References 21 publications

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

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

Synthesis by Reduction

Sodium Bis(methoxyethoxy)aluminium Hydride

Contact Info

Product

Resources

About

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

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