Removal of N-arylsulfonyl groups from hydroxy .alpha.-amino acids

Roemmele, Renee C.; Rapoport, Henry

doi:10.1021/jo00245a049

Cited by 116 publications

(58 citation statements)

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“…In order to preserve the amide linkage in the immediate precursor to the target photoprobe, it was necessary to manipulate the nitrogen-protecting groups early in the synthesis to produce an intermediate that could be deprotected under mild conditions. Thus, the mesityl-protecting group was removed by treatment with 30% HBr in acetic acid (23), and the resulting secondary nitrogen was reprotected as the corresponding N-(p-NO 2 -Cbz) derivative (21). The phthalimide was then removed by hydrazinolysis (24), and the resulting primary amine was converted to the corresponding N-Boc derivative (25).…”

Section: Methodsmentioning

confidence: 99%

Photoaffinity Labeling of a Cell Surface Polyamine Binding Protein

Felschow

MacDiarmid

Bardos

et al. 1995

Journal of Biological Chemistry

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Intracellular polyamine pools are partially maintained by an active transport apparatus that is specific for and regulated by polyamines. Although mammalian transport activity has been characterized by kinetic studies, the actual protein itself has yet to be identified, purified, or cloned. As one approach to this problem, we attempted photoaffinity labeling of plasma membrane proteins using two specifically designed and synthesized polyamine conjugates as photoprobes. The first is a spermidine conjugate bearing the photoreactive moiety 4-azidosalicylic acid at the N 4 position via an alkyl linkage, and the second is a norspermine conjugate with 4-azidosalicylic acid at the N 1 position via an acyl linkage. Labeling of murine L1210 lymphocytic leukemia cells was carried out at 4°C to promote selective alkylation of cell surface proteins. Separation of plasma membrane proteins from cells cross-linked with the N 4 -spermidine conjugate by SDS-polyacrylamide gel electrophoresis revealed two heavily labeled proteins at ϳ118 and ϳ50 kDa (designated p118 and p50, respectively). Band p118 was more well defined and much more intensely labeled. Analogous proteins were also observed in human U937 lymphoma cells. Specificity of labeling was strongly suggested by competition with polyamines and analogs during labeling and further indicated by the nearly identical labeling of the same protein by the N 1 -norspermine photoprobe but not by the unconjugated photoreagent. Neuraminidase pretreatment of L1210 cells increased mobility of the p118, suggesting that it was glycosylated and, thus, of plasma membrane origin. In transport-deficient L1210 cells, p118 and p50 were found to have a slightly higher molecular mass and were accompanied by a less distinct protein band (ϳ100 kDa). These findings indicate the presence of a polyamine binding protein at the surface of murine and human leukemia cells, which could be directly or indirectly related to the polyamine transport apparatus.

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Section: Methodsmentioning

confidence: 99%

Photoaffinity Labeling of a Cell Surface Polyamine Binding Protein

Felschow

MacDiarmid

Bardos

et al. 1995

Journal of Biological Chemistry

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“…A major advantage of the bis(ethyl)polyamines lies in the fact that their synthesis is extremely straightforward, and depends only on the availability of the appropriate parent polyamine backbone 41, 46,47. These syntheses can also be readily scaled up to pilot-plant quantities.…”

Section: Analogues Of the Natural Polyamines Spermidine And Sperminementioning

confidence: 99%

Recent Advances in the Development of Polyamine Analogues as Antitumor Agents

2009

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“…2 Cyanoethylation 5 followed by Raney nickel reduction 5 of the cyano groups affords the corresponding tetraamine in high yield, which is then tetramesitylated (2-mesitylenesulfonyl chloride, dichloromethane, 10% aqueous NaOH) 6 to afford the protected intermediate 7. Bis alkylation of 7 (Method A, NaH, 2.2 equiv of R-X) 2 affords the (bis)-alkylated intermediates, which are deprotected (30% HBr in AcOH) 7 to yield the pure desired target compounds 8-12 as the tetrahydrobromide salts following recrystallization from ethanol/water.…”

Section: Chemistrymentioning

confidence: 99%

“…Bis alkylation of 20 (NaH, 1.5 or 2.2 equiv of R-X) 2 afforded the (mono)-or (bis)-alkylated intermediates, respectively, which were deprotected (30% HBr in AcOH) 7 to yield the pure desired target compounds 21-25 as their tetra-hydrobromide salts following recrystallization from ethanol/water.…”

Section: Chemistrymentioning

confidence: 99%

Novel Alkylpolyamine Analogues that Possess Both Antitrypanosomal and Antimicrosporidial Activity

Zou¹,

Wu²,

Sirisoma³

et al. 2001

Bioorganic & Medicinal Chemistry Letters

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A novel series of alkyl-or aralkyl-substituted polyamine analogues was synthesized containing a 3-7-3 polyamine backbone. These analogues were evaluated in vitro, and in one case in vivo, for activity as antitrypanosomal agents, and for activity against opportunistic infection caused by Microsporidia. Compound 21 inhibits trypanosomal growth with an IC 50 as low as 31 nM, while compound 24 shows promising activity in vitro against trypanosomes, and against Microsporidia in vitro and in vivo.There is no doubt that significant advancements in anti-infective therapy have improved the quality of life in developed nations. However, in underdeveloped countries, there exist major infectious diseases that account for a large portion of global morbidity. Some of these diseases have the potential to become a threat to those living in North America. Tuberculosis claims an estimated 2 million lives each year, and drug-resistant strains originally found in New York and Russia are now being identified in other locations. Malaria, African trypanosomiasis and Leishmaniasis accounted for an additional 1,210,000 deaths in 1999. 1 Also of concern is the increasing incidence of opportunistic infections such as those caused by Pneumocystis carinii and strains of Microsporidia. Drug discovery efforts against the diseases mentioned above are limited because infected persons in underdeveloped areas cannot afford even a single course of therapy, or because the infected population represents too small of a drug market. Clearly, there is a need for new antiinfective agents that are potent, nontoxic and inexpensive to manufacture. We recently described the synthesis and evaluation of a small series of (bis)alkylated polyamines that possess promising antitrypanosomal effects in vitro. 2 Analogues possessing a 3-3-3 carbon skeleton (Fig. 1), such as BENSpm 1, CPENSpm 2, and CHENSpm 3 2,3 have significant antitumor effects in vitro and in vivo, but are inactive against cultured trypanosomes. By contrast, analogues with a 3-7-3-carbon skeleton, typified by MDL 27695 4, 4 CHE-3-7-3 5, 2,3 and bis-CH-3-7-3 6 2,3 are inactive as antitumor agents, but possess promising antitrypanosomal effects in vitro. We now report second generation compounds in the 3-7-3 series, their biological evaluation as anti-trypanosomal agents, and their activity against Microsporidia in vitro and in vivo. NIH Public Access Author ManuscriptBioorg Med Chem Lett. Author manuscript; available in PMC 2011 June 7. ChemistryThe syntheses leading to (bis)alkylated polyamines, which are outlined in Scheme 1, are facile and straight-forward, and as such are suitable for the efficient and cost-effective production of a variety of active analogues. The tetraamine 7 can be readily synthesized from 1,3-bis-[(amino)methyl]cyclohexane in three steps. 2 Cyanoethylation 5 followed by Raney nickel reduction 5 of the cyano groups affords the corresponding tetraamine in high yield, which is then tetramesitylated (2-mesitylenesulfonyl chloride, dichloromethane, 10% aqueous NaOH) 6...

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Removal of N-arylsulfonyl groups from hydroxy .alpha.-amino acids

Cited by 116 publications

References 0 publications

Photoaffinity Labeling of a Cell Surface Polyamine Binding Protein

Photoaffinity Labeling of a Cell Surface Polyamine Binding Protein

Recent Advances in the Development of Polyamine Analogues as Antitumor Agents

Novel Alkylpolyamine Analogues that Possess Both Antitrypanosomal and Antimicrosporidial Activity

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