General procedure for the synthesis of mono-N-acylated 1,6-diaminohexanes

Stahl, Glenn L.; Walter, Roderich; Smith, Clark W.

doi:10.1021/jo00405a045

Cited by 168 publications

(79 citation statements)

References 3 publications

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“…3 However, selective cleavage of the di-t-butylimidodicarbonate, oftenly found as valuable intermediates in Mitsunobu 4 and Gabriel type 5 processes towards the synthesis of several bio-active molecules, protected α-amino acids to mono-Boc compounds still lacks efficient and milder methods. Numerous methods are available for the removal of the Bocgroup, 7 including trifluoroacetic acid, 8 trimethylsilyl iodide, 9 hydrochloric acid in ethyl acetate, 10 ceric ammonium nitrate, 11 tin tetrachloride, 12 tetrabutylammonium fluoride, 13 zinc bromide, 14 boron trifluoride, 15 thermolytic removal 16 etc. However, there are very few methods for the selective cleavage 17a-f of the di-Boc protected α-amino acids to mono-Boc compounds.…”

Section: Introductionmentioning

confidence: 99%

Efficient and selective cleavage of the tert-butoxycarbonyl (Boc) group under basic condition

Mohapatra¹,

Durugkar²

2005

Arkivoc

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Section: Introductionmentioning

confidence: 99%

Efficient and selective cleavage of the tert-butoxycarbonyl (Boc) group under basic condition

Mohapatra¹,

Durugkar²

2005

Arkivoc

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“…In the next step, the key intermediate 6 was prepared in 91% yield by hydrogenation of the aldol adduct 5 with palladium-carbon (Pd-C) as catalyst, 34 followed by removal of the Boc group under acidic aqueous media. 35 Noteworthy, when the hydrogenation reaction lasted more than 20 min, the deoxygenation product was observed. The final product 1 was obtained by coupling the amine 6 and LA using benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate (PyBOP) and N,N-diisopropylethylamine (DIPEA) (Scheme 1).…”

Section: Synthesis Of Hybrid Compoundsmentioning

confidence: 99%

Two Novel Donepezil-Lipoic Acid Hybrids: Synthesis, Anticholinesterase and Antioxidant Activities and Theoretical Studies

Terra¹,

Silva²,

Tramarin³

et al. 2017

J. Braz. Chem. Soc.

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Alzheimer disease (AD) is a complex disease related to multiple pathogenic mechanisms. A strategy to develop effective drugs is based on the so-called multi-target directed ligands (MTDL) by using hybrid compounds. So, in the present study, we have designed and synthesized two hybrids, containing the indanone-piperidine moiety of donepezil, a drug approved for the treatment of AD, and the lipoic acid scaffold, an antioxidant compound endowed with neuroprotective effects. One hybrid was synthesized in four steps with 42% global yield, and the other hybrid in six steps with 19% global yield. The latter hybrid displayed moderate inhibitory activity against human acetylcholinesterase (hAChE) and greater activity against human butyrylcholinesterases (hBuChE). The selectivity for hBuChE was further rationalized by theoretical study. Importantly, the second hybrid showed a good antioxidant activity, exhibiting better ability in scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals than lipoic acid. Keywords: donepezil-lipoic acid hybrids, Alzheimer disease, multi-target directed ligands IntroductionAlzheimer disease (AD) is the most common cause of dementia in aging population. It was estimated that, in 2010, about 35.6 millions of people suffered from dementia worldwide, and it is expected that this number might triplicate in the next 40 years.1 Patients affected by AD experience progressive cognitive impairment, such as a decline in short-term memory, loss of speech, language and motor coordination. 2,3 AD is pathologically characterized by an extracellular deposition of β-amyloid (Aβ) peptide into senile plaques, intracellular formation of neurofibrillary tangles (NFTs) containing a hyperphosphorylated form of Tau protein, oxidative stress, mitochondrial abnormality, neuroinflammatory processes and neuronal loss, mainly affecting the frontal cortex and hippocampus. 4,5 AD is also characterized by a reduction of acetylcholine (ACh) levels, which is correlated with the cognitive symptoms. 6 The "cholinergic hypothesis", proposed in 1982 by Bartus et al.,7 postulated that the cognitive decline experienced by patients with AD resulted from a deficiency of acetylcholine or cholinergic neurotransmission. In humans, acetylcholine is degraded in the synaptic cleft by two main classes of cholinesterase enzymes: acetyl-(AChE) and butyryl- (BuChE) 8 cholinesterases. Near the amyloid plaques and neurofibrillary tangles, an extensive oxidative stress has been observed 9 which is a result of an altered balance of formation of reactive oxygen species (ROS) versus scavenging activity. 5,10 The production of ROS is also related to calcium homeostasis; the misbalance of calcium influx affects the mitochondrial Terra et al. 739 Vol. 29, No. 4, 2018 enzymes and ROS production is a normal part of the electron transport chain. However, excessive levels of these species damage proteins, lipids and nucleic acids. 9AD is a complex disease related to multiple pathogenic mechanisms involving different molecular targets. All the dru...

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“…17. Distilled 1,6-diaminohexane was dissolved in dioxane and to this solution, S-tert -butoxycarbonyl-4,6-dimethyl-2-mercapto pyrimidine, dissolved in dioxane, was added slowly over a period of 3 h and the reaction allowed to proceed overnight.…”

Section: N-acrylyl 26-diaminohexane Hc1mentioning

confidence: 99%

Effects of composition and polymerization conditions on crosslinked polymer supports based on N‐acrylyl pyrrolidine and N,N‐dimethyl acrylamide for peptide synthesis

Varadarajan

Fiat

1983

Biopolymers

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SynopsisPoly(N-acrylyl pyrrolidine-co-N,W-bis(acryly1) 1,2-diaminoethane-co-N-acrylyl 1,6-diamino hexane HCI) with 2,5,8,11, 12,15, and 20% degrees of crosslinking (DC) and poly-(N,A-dimethylacrylamide-co-N,N-bis(acryly1) 1,2-diaminoethane-co-N-acrylyl 1,6-diamino hexane HCl) with 2,5,10, and 15% DC have been synthesized in an entirely beaded form by reverse-phase suspension polymerization. The monomer-to-water ratio was kept constant for all these polymers. With the exception of 2% crosslinked resins in the PAP and PDMA groups, all the resins exhibited favorable swelling properties in solvents normally used for peptide synthesis and the percent incorporation of the first amino acid residue was close to 100 for DC of up to 20%. This is explained as due to the flexible and polar characteristics of the crosslinking agent, N,N'-bis(acryly1) 1,2-diaminoethane. Between 5 and 20% DC the degree of swelling of the resins changes only slightly with increasing DC. This effect of DC on the swelling and percent incorporation of the first amino acid residue is more favorable for peptide synthesis than in the case of divinyl benzene crosslinked poly(styrene).

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General procedure for the synthesis of mono-N-acylated 1,6-diaminohexanes

Cited by 168 publications

References 3 publications

Efficient and selective cleavage of the tert-butoxycarbonyl (Boc) group under basic condition

Efficient and selective cleavage of the tert-butoxycarbonyl (Boc) group under basic condition

Two Novel Donepezil-Lipoic Acid Hybrids: Synthesis, Anticholinesterase and Antioxidant Activities and Theoretical Studies

Effects of composition and polymerization conditions on crosslinked polymer supports based on N‐acrylyl pyrrolidine and N,N‐dimethyl acrylamide for peptide synthesis

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