Mild and Efficient Methods for the Reductive Cleavage of Nitrogen-Oxygen Bonds

Keck, Gary E.; Fleming, Steven A.; Nickell, D. G.; Weider, Paul R.

doi:10.1080/00397917908064153

Cited by 96 publications

(38 citation statements)

References 3 publications

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“…A range of different reagents have been used for reductive cleavage of N À O bonds, which included Li/4,4'-di-tert-butylbiphenyl (DTBB), [22,23] Na/Hg amalgam, [24,25] SmI 2 , [14,[26][27][28][29][30] TiCl 3 , [31][32][33][34] indium, [8,11] LiAlH 4 , [35,36] BH 3 , [37] [Mo(CO) 6 ], [13,24,[38][39][40][41][42][43][44][45][46][47][48][49] [Co 2 (CO) 8 ], [50] [Fe(CO) 5 ], [13,51] Zn/H +, [43,[52][53][54][55] NiB 2 , [56] Na 2 S 2 O 4 , [57] [TiA C H T U N G T R E N N U N G (iPrO) 4 ]/EtMgBr, [58] NiH 2 , [59] trimethylsilyl chloride/KI, …”

Section: Resultsmentioning

confidence: 99%

Synthesis and Application of a New Fluorous‐Tagged Ammonia Equivalent

Nielsen

Smith

Begtrup

et al. 2010

Chemistry A European J

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A novel fluorous-tagged ammonia equivalent has been developed. It is based on a nitrogen-oxygen bond, which can be cleaved in a traceless manner by a molybdenum complex or samarium diiodide. The application in the synthesis of ureas, amides, sulfonamides, and carbamates is described. The scope of the fluorous N-O linker is exemplified by the synthesis of itopride, a drug used for the treatment of functional dyspepsia. Itopride was synthesized with the aid of fluorous purification methods and the product was isolated in good overall yield, with high purity.

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Section: Resultsmentioning

confidence: 99%

Synthesis and Application of a New Fluorous‐Tagged Ammonia Equivalent

Nielsen

Smith

Begtrup

et al. 2010

Chemistry A European J

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“…The combined organic extracts were treated with charcoal, concentrated in vacuo, and evaporated once from carbon tetrachloride. The residual syrup was crystallized from 75 mL of EtOH/H,O by seeding and refrigeration to give 1.6 g (76%) of 7,a-dimethoxy-3,lla-dihydro-1 l-(methylthio)-5H-pyrrolo[2,1-c] [ A mixture of 144 mg (0.45 mmol) of 7,8-dimethoxy-3,lla-dihydro-ll-(methylthio)-5H-pyrrolo[2,l-c] [ 1,4] benzodiazepin-5-one, 30 mL of THF, 3 mL of saturated aqueous KH2P04, and aluminum amalgam prepared from 184 mg of aluminum foil according to the procedure of Keck et al (39) was stirred efficiently a t 0 "C for 18 h; HPLC indicated 65% conversion. The reaction was diluted with an additional 10 mL of THF, 1 mL of saturated aqueous KH2P04, and Al/Hg prepared from 61 mg of foil.…”

Section: 4]benzodiazepine-ll-thionementioning

confidence: 99%

Pyrrolo[1,4]benzodiazepine antitumor antibiotics: relationship of DNA alkylation and sequence specificity to the biological activity of natural and synthetic compounds

Hurley¹,

Reck

Thurston

et al. 1988

Chem. Res. Toxicol.

139

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The DNA alkylation and sequence specificity of a group of natural and synthetic pyrrolo- [1,4]benzodiazepines [P(1,4)Bs] were evaluated by using an exonuclease I11 stop assay, and the results were compared with in vitro and in vivo biological potency and antitumor activity. The P(1,4)B antibiotics are potent antitumor agents produced by various Actinomycetes, which are believed to mediate their cytotoxic effects by covalent bonding through N-2 of guanine in the minor groove of DNA. In this article we describe the results of a sensitive DNA alkylation assay using exonuclease I11 which permits both estimation of the extent of DNA modification as well as location of the precise guanines to which the drugs are covalently bound. Using this assay, we have evaluated a series of natural and synthetic compounds of the P(1,4)B class for their ability to bind to DNA and also determined their DNA sequence preference. The compounds included in this study are P(1,4)Bs carrying different substituents in the aromatic ring, having varying degrees of saturation in the five-membered ring, or differing in the stereochemistry a t C-lla. These same compounds were evaluated for in vitro cytotoxic activity against B16 melanoma cells, for potency in vivo in B6D2F1 mice (LDm), and for antitumor activity (ILS,) against P388 leukemia cells. A good correlation was found between extent of DNA alkylation and in vitro and in vivo potency. Furthermore, on the basis of electronic and steric considerations, it was possible to rationalize why those compounds that showed negligible biological activity were unable to bond covalently to DNA. Last, we have determined that the degree of saturation in the five-membered ring of the P(1,4)Bs has a significant effect on the DNA bonding reactivity and biological activity of this class of compounds.

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“…The harsh conditions needed for the hydrolysis of diketopiperazines caused the complete decomposition of 8. Thus by reductive cleavage with a Na/Hg amalgam [13], the N-O bond was severed, resulting in 9, a cyclic diamide of proline and a new chiral unnatural amino acid, in a 79% yield. This substance was then hydrolyzed into its components.…”

Section: Resultsmentioning

confidence: 99%

“…NMR spectra ( 1 H, 13 C and 2D experiments) were performed on Bruker AMX-400, AMX-300 or WP-200-SY FT-NMR spectrometers. The chemical shifts are reported in ppm on the δ scale relative to TMS (tetramethylsilane).…”

Section: Generalmentioning

confidence: 99%