Efficient and chemoselective alkylation of amines/amino acids using alcohols as alkylating reagents under mild conditions

Xu, Chu-Pei; Xiao, Zhen-Hua; Zhuo, Bi‐Qin; Wang, Yu‐Huang; Huang, Pei‐Qiang

doi:10.1039/c0cc01487g

Cited by 89 publications

(50 citation statements)

References 49 publications

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“…The N ‐hexyl ( 8 ), N ‐nonyl ( 10 ), and N ‐(6‐acetamidohexyl) ( 14 ) derivatives of DIR were prepared using the corresponding alkylamines. A very small amount of N ‐methyl DIR 6 was formed during the synthesis of 4 which involved hydrogenation in methanol . We also isolated a small amount of the C4 epimer ( l ‐ arabino configuration) of 9 , compound 11 , probably resulting from the epimerization of the aldehyde d ‐ 2 or the corresponding iminium salt during the reductive amination reaction.…”

Section: Resultssupporting

confidence: 88%

N‐Alkyl‐, 1‐C‐Alkyl‐, and 5‐C‐Alkyl‐1,5‐dideoxy‐1,5‐imino‐(l)‐ribitols as Galactosidase Inhibitors

et al. 2015

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A series of 1,5-dideoxy-1,5-imino-(l)-ribitol (DIR) derivatives carrying alkyl or functionalized alkyl groups were prepared and investigated as glycosidase inhibitors. These compounds were designed as simplified 4-epi-isofagomine (4-epi-IFG) mimics and were expected to behave as selective inhibitors of β-galactosidases. All compounds were indeed found to be highly selective for β-galactosidases versus α-glycosidases, as they generally did not inhibit coffee bean α-galactosidase or other α-glycosidases. Some compounds were also found to be inhibitors of almond β-glucosidase. The N-alkyl DIR derivatives were only modest inhibitors of bovine β-galactosidase, with IC50 values in the 30-700 μM range. Likewise, imino-L-ribitol substituted at the C1 position was found to be a weak inhibitor of this enzyme. In contrast, alkyl substitution at C5 resulted in enhanced β-galactosidase inhibitory activity by a factor of up to 1000, with at least six carbon atoms in the alkyl substituent. Remarkably, the 'pseudo-anomeric' configuration in this series does not appear to play a role. Human lysosomal β-galactosidase from leukocyte lysate was, however, poorly inhibited by all iminoribitol derivatives tested (IC50 values in the 100 μM range), while 4-epi-IFG was a good inhibitor of this enzyme. Two compounds were evaluated as pharmacological chaperones for a GM1-gangliosidosis cell line (R301Q mutation) and were found to enhance the mutant enzyme activity by factors up to 2.7-fold.

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Section: Resultssupporting

confidence: 88%

N‐Alkyl‐, 1‐C‐Alkyl‐, and 5‐C‐Alkyl‐1,5‐dideoxy‐1,5‐imino‐(l)‐ribitols as Galactosidase Inhibitors

et al. 2015

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“…Catalytic hydrogenation of 64 catalyzed by Pd(OH) 2 or Pd/C proceeded very slowly (Scheme 15a). With prolonged reaction time, multiple side products due to methylation of the free N -terminus 115 and reduction of phenyl rings were formed, which could not be separated from the desired product. To address this issue, an alternative route was explored by installing a protective group onto the N -terminus, which is stable under hydrogenation condition and yet known to be removable under mild conditions.…”

Section: Resultsmentioning

confidence: 99%

Obstacles and solutions for chemical synthesis of syndecan-3 (53–62) glycopeptides with two heparan sulfate chains

Yang

Yoshida

Yang

et al. 2016

Carbohydrate Research

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Proteoglycans play critical roles in many biological events. Due to their structural complexities, strategies towards synthesis of this class of glycopeptides bearing well-defined glycan chains are urgently needed. In this work, we give the full account of the synthesis of syndecan-3 glycopeptide (53–62) containing two different heparan sulfate chains. For assembly of glycans, a convergent 3+2+3 approach was developed producing two different octasaccharide amino acid cassettes, which were utilized towards syndecan-3 glycopeptides. The glycopeptides presented many obstacles for post-glycosylation manipulation, peptide elongation, and deprotection. Following screening of multiple synthetic sequences, a successful strategy was finally established by constructing partially deprotected single glycan chain containing glycopeptides first, followed by coupling of the glycan-bearing fragments and cleavage of the acyl protecting groups.

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“…[38] So far, only af ew examples of N-methylation under such hydrogenolytic deprotection or hydrogenation conditions have been reported and the application of the hydrogenation conditions in methanol as an effective methylation methodh ad not been appliedu ntil Huang et al published their results describing chemoselective alkylation of amines/amino acids. [39] Mechanistically,i nt he presence of Pd/C, methanoli so xidized to HCHO throughd ehydrogenation.T he reductivea minationo fH CHO with amines/amino acids affords the methylated products (Table 4).…”

Section: Methanol In Hydrogenolytic Deprotection/hydrogenationmentioning

confidence: 99%

Recent Advances in Methylation: A Guide for Selecting Methylation Reagents

Chen

2018

Chemistry A European J

201

121

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Methylation is a well‐known structural modification in organic and medicinal chemistry. This review summarizes recent advances in methylation by categorizing specific methylation reagents. The challenges of mono N‐methylation of aliphatic amines and N‐methylation of peptides are discussed. This review will be useful for chemists wanting to select the appropriate reagents for methylation chemistry. Based on the large diversity of methylation reagents and their wide scope, this review also broadens perspectives on which strategies to select for utilizing a particular methylation, resulting in an increased flexibility in synthetic route planning.

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Efficient and chemoselective alkylation of amines/amino acids using alcohols as alkylating reagents under mild conditions

Cited by 89 publications

References 49 publications

N‐Alkyl‐, 1‐C‐Alkyl‐, and 5‐C‐Alkyl‐1,5‐dideoxy‐1,5‐imino‐(l)‐ribitols as Galactosidase Inhibitors

N‐Alkyl‐, 1‐C‐Alkyl‐, and 5‐C‐Alkyl‐1,5‐dideoxy‐1,5‐imino‐(l)‐ribitols as Galactosidase Inhibitors

Obstacles and solutions for chemical synthesis of syndecan-3 (53–62) glycopeptides with two heparan sulfate chains

Recent Advances in Methylation: A Guide for Selecting Methylation Reagents

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