Total syntheses of (+)-P-3A, epi-(-)-P-3A, and (-)-desacetamido P-3A

Boger, Dale L.; Honda, Takeshi; Menezes, Royce F.; Colletti, Steven L.; Dang, Qun; Yang, Wenjin

doi:10.1021/ja00080a010

Cited by 58 publications

(53 citation statements)

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“…Our synthetic endeavours began with the thermal Huisgen cycloaddition (Dondoni et al 2004) of the known phosphonate 10 (Vuilhorgne et al 2003) and serine-derived azide 9a (Boger et al 1994). Gratifyingly, this reaction gave both of the desired triazole regioisomers 11a and 12a (Scheme 1; Table 1), which were easily separable by column chromatography.…”

Section: Resultsmentioning

confidence: 99%

“…This compound was synthesised according to the method of Boger (Boger et al 1994) with slight modifications. Following the general procedure with Boc-Ser-OMe (3.61 g, 16.5 mmol), flash chromatography and elution with 1:4 Et 2 O/hexanes gave 9a as a colourless oil (2.90 g, 72% (Dondoni et al 2004) ?36.0°(c 0.6, CHCl 3 )].…”

Section: (S)-methyl 3-azido-2-(t-butoxycarbonylamino)propanoate (9a)mentioning

confidence: 99%

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Stable triazolylphosphonate analogues of phosphohistidine

et al. 2011

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Histidine-phosphorylated proteins and the corresponding kinases are important components of bacterial and eukaryotic cell-signalling pathways, and are therefore potential drug targets. The study of these biomolecules has been hampered by the lability of the phosphoramidate functional group in the phosphohistidines and the lack of generic antibodies. Herein, the design and concise synthesis of stable triazolylphosphonate analogues of N1- and N3-phosphohistidine, and derivatives suitable for bioconjugation, are described.

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Section: Resultsmentioning

confidence: 99%

Section: (S)-methyl 3-azido-2-(t-butoxycarbonylamino)propanoate (9a)mentioning

confidence: 99%

Stable triazolylphosphonate analogues of phosphohistidine

et al. 2011

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“…['301 REVIEWS DNA Alkylations Fig. 40. Side and rear views of the CBQ boat (left, X-ray structure analysis [128,129]), CBQ halfChdir(middle), andCBI(r1ght. X-ray structure analysis[ll8]) conformations.…”

Section: Additional Subtle Features Contributing To the Dna Alkylatiomentioning

confidence: 99%

CC‐1065 and the Duocarmycins: Understanding their Biological Function through Mechanistic Studies

Boger

Johnson

1996

Angew. Chem. Int. Ed. Engl.

Self Cite

327

279

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Merely reversing the amangelnetit ot the DNA-binding atructural elements ( D S A -C D P l 2~C D P I 2 -D S A )c a~i x h a DNA alkylating agent to behabe like the enailtiornet-ofthe natural product. although the alkylation unit has the contifuration lound in nature. Model studies on the binding of the enantiorners to DNA provide an explanation. We review here studies defining the DNA alkylation properties of a class of potent antitumor antibiotics that includes CC-1065 and the duocarmycins, as well as investigations that delineate fundamental relationships between their structure, functional reactivity, and biological properties. In conjunction with the study of the natural products themselves, the examination of synthetic agents containing deep-seated structural changes, the unnatural enantiomers of the natural products, and related analogs has defined the structural basis for the sequence selective alkylation of duplex DNA and proved to be the key to understanding the fundamental relationships between chemical structure, functional reactivity, and biological properties. The characteristic DNA alkylation proceeds by reversible, stereoelectronically controlled adenine-N3 addition to the least substituted carbon of the activated cyclopropane within AT-rich minor groove sites. Both the natural and unnatural enantiomers alkylate DNA, and the sequence selectivity of both is controlled and dominated by the preferential noncovalent binding of the agents within the narrower, deeper, AT-rich minor groove and the steric accessibility to the alkylation site on penetration of this groove. Among the fundamental relationships between structure and properties, the most striking is the direct relationship between chemical or functional stability and biological potency. Within a short time, simplified and readily accessible synthetic agents rationally based on the natural product leads have been developed, which exhibit comparable and exceptional biological potency (IC50 = 50 to 51 PM) and improved efficacy. The fundamental relationships that have been defined to date can be expected to provide the foundation for future developments and advances.

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“…Serine is a convenient precursor for the synthesis of the azido derivative of alanine. Several different methods were previously developed for introducing the azido moiety to a serine derivative: (i) ring opening of cyclic N-(phenyl fluoride) serine sulfamidate [18][19][20], (ii) opening of (S)-3-amino-2-oxetanone [21], (iii) mild bromination of the hydroxyl group followed by azidation [22][23][24][25], (iv) Mitsunobu reaction treatment with triphenylphosphine (PPh 3 ), hydrazoic acid and azodicarboxylate [26][27][28][29][30][31][32][33][34][35], and (v) activation of the hydroxyl group by mesyl chloride (MsCl) [35][36][37][38] or tosyl chloride [39], followed by substitution with sodium azide. In addition, the synthesis of azidoalanine starting from N-protected asparagine represents a different but straightforward approach.…”

Section: Introductionmentioning

confidence: 99%

Optimized syntheses of Fmoc azido amino acids for the preparation of azidopeptides

Pícha

Budêšínský

Macháčková

et al. 2017

Journal of Peptide Science

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The rise of CuI‐catalyzed click chemistry has initiated an increased demand for azido and alkyne derivatives of amino acid as precursors for the synthesis of clicked peptides. However, the use of azido and alkyne amino acids in peptide chemistry is complicated by their high cost. For this reason, we investigated the possibility of the in‐house preparation of a set of five Fmoc azido amino acids: β‐azido l‐alanine and d‐alanine, γ‐azido l‐homoalanine, δ‐azido l‐ornithine and ω‐azido l‐lysine. We investigated several reaction pathways described in the literature, suggested several improvements and proposed several alternative routes for the synthesis of these compounds in high purity. Here, we demonstrate that multigram quantities of these Fmoc azido amino acids can be prepared within a week or two and at user‐friendly costs. We also incorporated these azido amino acids into several model tripeptides, and we observed the formation of a new elimination product of the azido moiety upon conditions of prolonged couplings with 2‐(1H‐benzotriazol‐1‐yl)‐1,1,3,3‐tetramethyluronium hexafluorophosphate/DIPEA. We hope that our detailed synthetic protocols will inspire some peptide chemists to prepare these Fmoc azido acids in their laboratories and will assist them in avoiding the too extensive costs of azidopeptide syntheses.Experimental procedures and/or analytical data for compounds 3–5, 20, 25, 26, 30 and 43–47 are provided in the supporting information. © 2017 The Authors Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd.

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Total syntheses of (+)-P-3A, epi-(-)-P-3A, and (-)-desacetamido P-3A

Cited by 58 publications

References 0 publications

Stable triazolylphosphonate analogues of phosphohistidine

Stable triazolylphosphonate analogues of phosphohistidine

CC‐1065 and the Duocarmycins: Understanding their Biological Function through Mechanistic Studies

Optimized syntheses of Fmoc azido amino acids for the preparation of azidopeptides

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