Intramolecular reactions of N-acyliminium intermediates

Speckamp, W. N.; Hiemstra, Henk

doi:10.1016/s0040-4020(01)82334-6

Cited by 577 publications

(206 citation statements)

References 273 publications

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“…Instead, we anticipated a specific role for the N-acyl enamine functional group. It is known that electrophilic N-acyliminium ions can be generated from N-acyl enamines under acidic conditions (30). As delineated in Fig.…”

Section: Discussionmentioning

confidence: 99%

“…6A) under denaturing conditions. It is known that, whereas thiol adducts (X ϭ S; Cys) are stable, carboxylate (X ϭ O 2 C; Asp, Glu) and alkoxy (X ϭ O; Thr, Ser, Tyr) adducts can generate N-acyliminium ions by fragmentation under neutral or acidic conditions (30). Expecting that adduct C would be more stable within the confines of the folded protein, we purified the putative covalent complex under non-denaturing conditions (glycerol density gradient centrifugation).…”

Section: Discussionmentioning

confidence: 99%

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Salicylihalamide A Inhibits the V0 Sector of the V-ATPase through a Mechanism Distinct from Bafilomycin A1

Xie

Padrón

Liao

et al. 2004

Journal of Biological Chemistry

113

105

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The newly identified specific V-ATPase inhibitor, salicylihalamide A, is distinct from any previously identified V-ATPase inhibitors in that it inhibits only mammalian V-ATPases, but not those from yeast or other fungi (Boyd, M. R., Farina, C., Belfiore, P., Gagliardi, S., Kim Acidification of intracellular compartments of eukaryotes is essential for many cellular processes, including receptor-mediated endocytosis, protein degradation in lysosomes, processing of hormones, uptake, and storage of neurotransmitters, and entry of many viruses into cells. The control of pH within these intracellular compartments is mediated by vacuolar H ϩ -translocating ATPases, which acidify organelles of both constitutive and regulated secretory pathways (1-5). V-ATPases 1 are also found in the plasma membrane of certain cells where they are responsible for cell type-specific processes, including urinary acidification and osteoclast-mediated bone resorption (6, 7). The V-type ATPases are among the most widely distributed ATP-driven ion pumps in nature, present in all eukaryotic cells and in various bacteria. Within eukaryotic cells, the structure of these proton pumps is highly conserved from yeast to human, as a multiple subunit complex with a molecular mass exceeding 850 kDa. They contain at least 13 different subunits with various copy numbers, which are organized into two distinct domains, a peripheral V 1 domain that is the catalytic sector and a transmembrane V 0 domain that constitutes the proton channel.V-pumps are regulated at various levels from transcription and protein synthesis to the regulation of its enzymatic activity through a variety of mechanisms. The most unique regulation mechanism for V-pumps is the reversible dissociation and association of V 1 and V 0 in response to energy demand, which has been extensively studied and clearly demonstrated in yeast and tobacco hornworm (8 -10). However, whether this reversible dissociation and association of V-ATPase domains exists in mammals as a regulatory mechanism and, if it does, how this process is regulated, is not clear at the present.During the past two decades, the importance of this class of ATPases for many critical cellular functions has become increasingly appreciated. Furthermore, the elucidation of the physiological role of V-pumps has revealed the important role these proteins play in a wide array of pathological processes, such as osteoporosis (6), certain renal diseases (7, 11), HIV infection (12), and tumor metastasis (5). The food vacuole of certain parasites is acidified by V-type proton pumps, and disruption of the acidification of this intracellular compartment results in death of the organism. Thus, the V-type pumps are potential targets for the development of pharmacological agents to treat a variety of diseases.Because of the importance of V-ATPases as a potential therapeutic target, the mechanism by which inhibitors of V-ATPase interfere with pump function has become an area of great scientific interest. Over the past 15 years a few specific VATP...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Salicylihalamide A Inhibits the V0 Sector of the V-ATPase through a Mechanism Distinct from Bafilomycin A1

Xie

Padrón

Liao

et al. 2004

Journal of Biological Chemistry

113

105

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“…Tautomerisation of N-acylimines into the corresponding enamides is a well-known phenomenon. 7,43 In a few cases (compounds 5c, 5d, 5h and 5k), the amidinium salts transformation to the corresponding enamides or N-acylimines is probably so rapid that attempts to separate the polar salts from less polar compounds by extraction with toluene failed. These conclusions were confirmed by the observation that not only phosphonium salts 4, but also amidinium or guanidinium salts 5 and enamides 6 all react easily with β-dicarbonyl compounds in the presence of the corresponding base under microwave irradiation at 60 o C to give the expected product of α-amidoalkylation of the corresponding enolate anion (Scheme 5, Table 3).…”

Section: Methodsmentioning

confidence: 99%

N-(1-acyloaminoalkyl)amidinium salts derived from DBU or related bases as reactive intermediates in α-amidoalkylation reactions

Październiok-Holewa¹,

Adámek²,

Zielińska³

et al. 2012

Arkivoc

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Abstract1-(N-Acylamino)alkyltriphenylphosphonium salts 4, when treated with DBU, DBN or TBD in CD 3 CN or MeCN, were transformed immediately into the corresponding 1-(Nacylamino)alkylamidinium or guanidinium salts 5. Salts 5 with a proton at the α-position underwent slow transformation to the corresponding enamides 6. 1-(NAcylamino)alkyltriphenylphosphonium salts 4, amidinium or guanidinium salts 5, as well as enamides 6 reacted readily with β-dicarbonyl compounds in the presence of corresponding base under microwave irradiation at 60 o C to give the expected product of α-amidoalkylation of the enolate anion. The role of 1-(N-acylamino)alkylamidinium or guanidinium salts 5 as reactive intermediates in α-amidoalkylation with 1-(N-acylamino)alkyltriphenylphosphonium salts is discussed.

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“…The solution was filtered and evaporated in vacua to leave a residue, which was purified by column chromatography. The cyclized products (13,14) produced in the oxidation of the Boc-ornithine and Boc-lysine series (5a-c, 6a-c) were eluted faster than the desired imide products. The results are summarized in Table I.…”

Section: Methodsmentioning

confidence: 99%

Chemical conversion of L-.ALPHA.,.OMEGA.-diamino acids to L-.OMEGA.-carbamoyl-.ALPHA.-amino acids by ruthenium tetroxide oxidation.

Yoshifuji

Tanaka

Nitta

1987

CHEMICAL & PHARMACEUTICAL BULLETIN

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Intramolecular reactions of N-acyliminium intermediates

Cited by 577 publications

References 273 publications

Salicylihalamide A Inhibits the V0 Sector of the V-ATPase through a Mechanism Distinct from Bafilomycin A1

Salicylihalamide A Inhibits the V0 Sector of the V-ATPase through a Mechanism Distinct from Bafilomycin A1

N-(1-acyloaminoalkyl)amidinium salts derived from DBU or related bases as reactive intermediates in α-amidoalkylation reactions

Chemical conversion of L-.ALPHA.,.OMEGA.-diamino acids to L-.OMEGA.-carbamoyl-.ALPHA.-amino acids by ruthenium tetroxide oxidation.

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