A new mild method for the synthesis of amidines

Lange, Udo E. W.; Schäfer, Bernd; Baucke, Dorit; Buschmann, Ernst; Mack, Helmut

doi:10.1016/s0040-4039(99)01460-4

Cited by 52 publications

(46 citation statements)

References 27 publications

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“…17 Alternatively, we obtained α-methyl serine as a generous gift from Ajinomoto Co., Japan, and converted this substance into α-methyl cysteine by a published procedure. 18 Gram quantities of this amino acid was obtained in high enantiomeric purity and was condensed with the known nitrile ( 7 ) 19 to provide the thiazoline-thiazole subunit ( 8 ) in high yield.…”

Section: Resultsmentioning

confidence: 99%

Total Synthesis and Biological Mode of Action of Largazole: A Potent Class I Histone Deacetylase Inhibitor

et al. 2008

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The efficient total synthesis of the recently described natural substance largazole (1) and it’s active metabolite largazole thiol (2) is described. The synthesis required eight linear steps and proceeded in 37% overall yield. It is demonstrated that largazole is a pro-drug, that is activated by removal of the octanoyl residue from the 3-hydroxy-7-mercaptohept-4-enoic acid moiety to generate the active metabolite largazole thiol (2) which is an extraordinarily potent Class I histone deacetylase inhibitor. Synthetic largazole and the largazole thiol (2) have been evaluated side-by-side with FK228 and SAHA for inhibition of HDACs 1, 2, 3, and 6. Largazole and largazole thiol were further assayed for cytotoxic activity against a panel of chemoresistant melanoma cell lines and it was found that largazole is substantially more cytotoxic than largazole thiol; this difference being attributed to differences in cell permeability of the two substances, respectively.

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Section: Resultsmentioning

confidence: 99%

Total Synthesis and Biological Mode of Action of Largazole: A Potent Class I Histone Deacetylase Inhibitor

et al. 2008

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“…Compound 5a wasc onverted into the corresponding amidine 6a by catalytic hydrogenation, using ap rotocol by Judkins et al [15] Due to the instability of the OBn substituent toward hydrogenation, this method was clearly not applicable to 5b.A lthough there are non-hydrogenative methods for the direct conversion of nitrilesi nto amidines, [16,17] we think that amidoximes constitute very convenient precursors for the synthesis of amidines. Our synthetic route started from the corresponding nitriles (exceptf or 2c,f or which the corresponding amidine 6c was commercially available).…”

Section: Synthesismentioning

confidence: 99%

Fragment Growing to Design Optimized Inhibitors for Human Blood Group B Galactosyltransferase (GTB)

et al. 2019

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Human blood group B galactosyltransferase (GTB) catalyzes the galactosylation of the H antigen and is responsible for the formation of the blood group antigen of phenotype B. The ABO blood group system is well studied and routinely serotyped before transfusion and transplantation. Blood type subgroups have been repeatedly linked to an increased occurrence of diseases (e.g., a highly increased incidence rate for pancreatic cancer for individuals with blood group phenotype B). 3‐Phenyl‐5‐(piperazin‐1‐yl)‐1,2,4‐thiadiazole 1 has previously been described to inhibit GTB with a Ki value of 800 μm. In this work, we describe a computer‐guided fragment‐growing approach for the optimization of this fragment that was subsequently realized by synthesizing the most promising ligands. Enlarging the phenyl moiety of fragment 1 to a naphthyl moiety resulted in ligand 3‐(naphthalene‐1‐yl)‐5‐(piperazin‐1‐yl)‐1,2,4‐thiadiazole 2 a, which shows a threefold improvement in binding affinity (Ki=271 μm).

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“…Em alguns casos, a amônia tem sido substituída por acetato de amônio, o que aumenta o tempo reacional, que pode chegar até 48 h, e altera o rendimento da reação. A grande desvantagem do método é o alto custo da N-acetilcisteína 42 (Esquema 7).…”

Section: Esquema 3 Estrutura Da Distamicina Dos Santos Et Alunclassified

Principais métodos de síntese de amidinas

Santos¹,

Bernardino²,

Souza³

2006

Quím. Nova

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Recebido em 8/6/05; aceito em 6/1/06; publicado na web em 6/7/06 SYNTHETIC APPROACHES TO AMIDINES. The amidine functional group is found in a wide range of natural products and is biologically active against several pathogens. In addition, amidines have long been regarded as useful intermediates in the synthesis of heterocyclic compounds. Consequently, a great number of methods have been developed for the preparation of amidines. Pinner's method is the most commonly used. Conventional methods include: -the addition of metal amides or amines to nitriles, the addition of amines to imido esters and the condensation of amides with amines in the presence of halogenating reagents. In this report, the main methods for synthesis of amidines will be described.

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A new mild method for the synthesis of amidines

Cited by 52 publications

References 27 publications

Total Synthesis and Biological Mode of Action of Largazole: A Potent Class I Histone Deacetylase Inhibitor

Total Synthesis and Biological Mode of Action of Largazole: A Potent Class I Histone Deacetylase Inhibitor

Fragment Growing to Design Optimized Inhibitors for Human Blood Group B Galactosyltransferase (GTB)

Principais métodos de síntese de amidinas

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