Synthesis of the bradykinin B1 antagonist [desArg10]HOE 140 on 2-chlorotrityl resin

Rovero, Paolo; Viganò, Stefania; Pegoraro, Stefano; Quartara, Laura

doi:10.1007/bf00119994

Cited by 31 publications

(29 citation statements)

References 20 publications

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“…This strategy reduces the risk of diketopiperazine formation by intramolecular aminolysis. [34] The Aaa4 was coupled with PyBOP (2 equiv), HOAt (2 equiv), and DIEA (6 equiv). Protected peptide fragments were released from the CTC resin by cleavage with TFA-DCM (1:99).…”

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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“…It can be used for the preparation of both protected and unprotected peptides. The main advantages of its use are: (i) allows for release of the peptide under mild acidic conditions [1% Trifluoroacetic Acid (TFA), Hexafluoro-2-Propanol (HFIP), TFE] [23]; (ii) minimizes the formation of Diketopiperazine (DKP) [24,25]; (iii) minimizes racemization during the incorporation of the first amino acid; and (iv) allows for the incorporation of partially protected amino acids through the side chain or the amino function [26,27].…”

Section: Introductionmentioning

confidence: 99%

Chlorotrityl Chloride (CTC) Resin as a Reusable Carboxyl Protecting Group

et al. 2007

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Chlorotrityl Chloride (CTC) resin is one of the most useful resins for the solid-phase synthesis of C-terminal acid peptides. CTC resin can be used for the preparation of both protected and unprotected peptides. Herein, the use of CTC resin as a reusable mild protecting group of carboxylic acids is introduced. Temporary protection of carboxylic acids in solution is not a straightforward process, but the use of CTC resin is shown to be an alternative to classic solution procedures. Regeneration of the CTC resin after cleavage of the target compounds is feasible, which allows the reuse of the resin. Applications described herein encompass the preparation of noncommercial amino acids as well as complex dipeptides.

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“…[13] Combinations of -and -amino acids, as well as the presence of one Nmethylamino acid -or, worse still, two N-methylamino acids -favour DKP formation and must be treated carefully. A number of general precautions have been described, such as the use of highly steric hindered resins (e.g., CTC resin, which protects the carboxylic function [14][15][16] ) or protecting groups that are removed under acidic or almost neutral conditions. [17][18][19][20] In depsipeptide syntheses, the presence of labile ester bonds in the peptide chain provides another potential point for DKP formation.…”

Section: Dkp Formation Throughout the Sequencementioning

confidence: 99%

“…b) To minimize the risk of DKP formation by: i) avoiding Cys(Me) as the C terminus because it is very prone to give DKPs as a result of the acidity of its β-proton, ii) using Alloc and pNZ groups instead of the Fmoc group, [19,20] iii) using CTC resin, which because of its steric hindrance gives better results than Wang resin, [15,16] and iv) restricting the flexibility of the peptide chain by, for example, using the dimerization approach. [4] c) To choose the chemistry carefully after the ester bond has been formed.…”

Section: Conclusion and Final Strategymentioning

confidence: 99%

Oxathiocoraline: Lessons to be Learned from the Synthesis of ComplexN‐Methylated Depsipeptides

2009

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Investigations into the synthesis of oxathiocoraline, a bicyclic depsipeptide with C2 symmetry, revealed a number of unexpected side‐reactions that could not be circumvented by classical or standard means. This cyclodepsipeptide has a large number of N‐methyl amino acids coexisting with two ester bonds and also shows a branched structure; these features hinder its synthesis. In addition, complexity is further increased because of the presence of a large number of non‐commercially available cysteines and heterocyclic moieties. Here we describe the general points that should be addressed when attempting the synthesis of a cyclodepsipeptide, such as strategies to prevent or minimize diketopiperazine formation, β‐elimination, and oxidation byproducts. The optimum design includes a suitable solid support, the choice of the best starting point for the synthesis (first amino acid to anchor to the resin) and a set of compatible and/or protecting groups and coupling reagents.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

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Synthesis of the bradykinin B1 antagonist [desArg10]HOE 140 on 2-chlorotrityl resin

Cited by 31 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

Chlorotrityl Chloride (CTC) Resin as a Reusable Carboxyl Protecting Group

Oxathiocoraline: Lessons to be Learned from the Synthesis of ComplexN‐Methylated Depsipeptides

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