On the use of PyAOP, a phosphonium salt derived from HOAt, in solid-phase peptide synthesis

Alberício, Fernando; Cases, Marta; Alsina, Jordi; Triolo, Salvatore A.; Carpino, Louis A.; Kates, Steven A.

doi:10.1016/s0040-4039(97)01011-3

Cited by 156 publications

(119 citation statements)

References 20 publications

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“…[28,29] Then, the Fmoc-Aaa2-OH (2 equiv) was carried out with an equimolar amount of PyBOP/ HOAt and a double amount of DIEA in DMF for 1 h. This method ology is one of the most effective for the coupling of FmocAaa-OH on NMeAaa because it combines a reactive standalone coupling reagent (PyBOP) [30] with an excellent leaving group (HOAt). [31] Furthermore, PyBOP is relatively inexpensive compared to PyAOP, [32] which is the phosphonium salt derived from HOAt. After the coupling, the chloranil test [33] was carried out and when positive the coupling was repeated in the same conditions, otherwise the process was continued.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Structure–Activity Relationship of Cytotoxic Marine Cyclodepsipeptide IB‐01212 Analogues

et al. 2007

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Several recently discovered marine products have remarkable in vitro and in vivo anticancer profiles against a wide range of tumor cell lines. Some of these compounds are currently in clinical trials. These compounds show complex structures and mechanisms of action of interest. Herein, we describe the preparation of a series of totally synthetic molecules that are structurally related to the natural marine product IB‐01212 and evaluated them as antitumor agents. For this, total solid‐phase syntheses of the products were performed in parallel by two distinct routes: linear synthesis and convergent synthesis. Structural modifications were introduced in several residue positions to afford 21 IB‐01212 analogues for structure–relationship studies. An increase in the number of methyl groups in the macrocycle enhanced cytotoxic activity. Also, the replacement of an ester bond by an amide bond favored antitumor activity against several human cell lines. In addition, the L configuration analogues were more active against all the tumor cell lines than those containing the D configuration. A significant increase in the size and asymmetry of the macrocycle diminished biological activity with respect to that of IB‐01212. These results are of great value for the discovery of new and more effective anticancer agents.

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Section: Resultsmentioning

confidence: 99%

Synthesis and Structure–Activity Relationship of Cytotoxic Marine Cyclodepsipeptide IB‐01212 Analogues

et al. 2007

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“…Thereafter, the methyl ester of 75 was saponified to carboxylic acid 77. Amino acid 77 was then subjected to PyAOP-mediated amide formation (49) to yield cyclodepsipeptide 79 in good yield. Cyclopdepsipeptide 79 was presumably differentiated from apratoxin A only by the presence of the C35 O-TBS group.…”

Section: Resultsmentioning

confidence: 99%

Total synthesis of the marine cyanobacterial cyclodepsipeptide apratoxin A

Chen

Forsyth

2004

Proc. Natl. Acad. Sci. U.S.A.

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“…PyAOP is utilized here to prevent guanidylation of the amino group which can occur with amidine-based coupling agents like TBTU and HATU. 71 …”

Section: Experimental and Theoretical Methods Peptide Synthesismentioning

confidence: 99%

Vibrational circular dichroism and IR spectral analysis as a test of theoretical conformational modeling for a cyclic hexapeptide

et al. 2008

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A model cyclohexapeptide, cyclo-(Phe-(D)Pro-Gly-Arg-Gly-Asp) was synthesized and its IR and VCD spectra were used as a test of density functional theory (DFT) level predictions of spectral intensities for a peptide with a nonrepeating but partially constricted conformation. Peptide structure and flexibility was estimated by molecular dynamics (MD) simulations and the spectra were simulated using full quantum mechanical (QM) approaches for the complete peptide and for simplified models with truncated side chains. After simulated annealing, the backbone conformation of the ring structure is relatively stable, consisting of a normal beta-turn and a tight loop (no H-bond) which does not vary over short trajectories. Only in quite long MD runs at high temperatures do other conformations appear. MD simulations were carried out for the cyclic peptide in water and in TFE, which match experimental solvents, as well as with and without protonation of the Asp carboxyl group. DFT spectral simulations were made using the annealed structure and were extended to include basis set variation, to determine an optimal computational approach, and solvent simulation with a polarized continuum model (PCM). Stepwise full DFT simulation of spectra was done for various sequences with the same backbone geometry but based on (1) solely Gly residues, (2) Ala substitution except Gly and Pro, and (3) complete sequences with side chains. Additionally, a selection of structures was used to compute IR and VCD spectra with the optimal method to determine structural variation effects. The side chains, especially the Asp-COOH and Arg-NH(2) transitions, had an impact on the computed amide frequencies, IR intensities and VCD pattern. Since experimentally these groups would have little chirality, due to conformational variation, they do not impact the observed VCD spectra. Correcting for frequency shifts, the Ala model for the cyclopeptide gives the clearest representation of the amide VCD. The experimental sign pattern for the amide I' band in D(2)O and also the sharper, more intense amide I VCD band in TFE was seen to some degree in one conformer with Type II' turns, but the data favor a mix of structures.

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On the use of PyAOP, a phosphonium salt derived from HOAt, in solid-phase peptide synthesis

Cited by 156 publications

References 20 publications

Synthesis and Structure–Activity Relationship of Cytotoxic Marine Cyclodepsipeptide IB‐01212 Analogues

Synthesis and Structure–Activity Relationship of Cytotoxic Marine Cyclodepsipeptide IB‐01212 Analogues

Total synthesis of the marine cyanobacterial cyclodepsipeptide apratoxin A

Vibrational circular dichroism and IR spectral analysis as a test of theoretical conformational modeling for a cyclic hexapeptide

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