Diastereoselective synthesis of novel aza-diketopiperazines via a domino cyclohydrocarbonylation/addition process (original) (raw)

Synthesis of Cross-linkable 2, 5-Diketopiperazine Derivatives

Letters in Organic Chemistry, 2015

Synthesis of cross-linkable diketopiperadine derivatives is described. Cross-linkable a-amino acid methyl esters were subjected to peptide synthesis with Boc-protected glycine or L-tyrosine. No protections of cross-linkable functional groups (catechol and phenylazide) are necessary for constructions of diketopiperazine skeleton.

Solidphase synthesis of diketopiperazines, useful scaffolds for combinatorial chemistry

Tetrahedron Letters, 1998

Diketopiperazines, which are cyclic dipeptides, are often formed by a side reaction of solid-phase peptide synthesis. Using the new “Backbone Amide Linker,” this chemistry can be conveniently harnessed for the intentional preparation of diketopiperazines. These products will be useful scaffolds for combinatorial chemistry, since they incorporate three different points of diversity: both amino acid side-chains and one (of the two)

Convergent Synthesis of Complex Diketopiperazines Derived from Pipecolic Acid Scaffolds and Parallel Screening against GPCR Targets

The Journal of Organic Chemistry, 2006

1. General Experimental Information: 1 H NMR and 13 C spectra were recorded at 400 MHz and 100.0 MHz respectively at ambient temperature with CDCl 3 as solvent unless otherwise stated. Chemical shifts are reported in parts per million relative to CDCl 3 (1 H, δ 7.26; 13 C, δ 77.0). Data are reported as follows: chemical shift, multiplicity (overlp=overlapping, s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad), coupling constant, and integration. All 13 C NMR spectra were recorded with complete proton decoupling. Optical rotations were recorded at 589 nm, and are reported as [α] D 20 (concentration in grams/100 mL solvent). Analytical and preparative HPLC were performed with a mass spectrometer, diode array, and a ELS detector. An Xterra 4.6 x 30 mm RP 8 column was used for analytical HPLC and an Xterra 19 x 50 mm RP 18 column was used for preparative HPLC. Analytical thin layer chromatography was performed on 0.25 mm silica gel 60-A plates. Methylene chloride, THF and toluene were purified by passing through two packed columns of neutral alumina. Microwave reactions were performed using the Discover™ Explorer System. 2. Sc(OTf) 3-Catalyzed Aza-annulation Reactions. (2S,5S,6S)-methyl 6-(4-bromophenyl)-1-(2,2,2-trifluoroacetyl)-1,2,5,6-tetrahydro-5methylpyridine-2-carboxylate (trans-8a): This compound was synthesized using general procedure 1 described in the Experimental Section of the paper. Yield 81%. Colorless oil; [α] D 20-82.0 o (c = 0.2, CHCl 3); IR (thin film) ν

Synthesis and biological evaluation of a post-synthetically modified Trp-based diketopiperazine

MedChemComm, 2013

A series of C2-arylated analogues of the diketopiperazine brevianamide F has been synthesized using a mild Pd-catalyzed CH-activation procedure. Biological evaluation of the new derivatives in different cell lines shows that this modification is responsible for the remarkable change in activity, turning a mild antibiotic and antifungal natural product (brevianamide F) into novel antitumoral compounds. Furthermore, the approach stated represents a new straightforward and versatile methodology with promising applications in peptidomimetics and medicinal chemistry.

A facile and effective synthesis of lipophilic 2,6-diketopiperazine analogues

Tetrahedron, 2008

Adamantane and cyclooctane lipophilic 2,6-diketopiperazines (2,6-DKPs) have been prepared by a simple and effective method, including the synthesis of the corresponding iminodiacetic amido-ester derivatives and their intramolecular cyclization. In this method, the key step of the imide formation was accomplished by a novel base-induced cyclization protocol, which involved the treatment of amido-ester 2,6-DKP precursors with potassium bis(trimethylsilyl)amide. Moreover, the cyclization methodology used allowed the synthesis of the respective 1-functionalized 2,6-DKPs in one pot and in excellent yields when the same primary amido-esters were treated with the previous base and the intermediate potassium imidate salts were then reacted with the electrophile benzyl bromoacetate. Hydrogenolysis of the benzyl 2,6-diketopiperazine acetates afforded the respective carboxylic acids, which constitute versatile intermediates in the synthesis of peptidomimetics and other bioactive molecules concerning our pharmacological studies.