Phosphine-Initiated General Base Catalysis: Facile Access to Benzannulated 1,3-Diheteroatom Five-Membered Rings via Double-Michael Reactions of Allenes

Regioselective transformation of alkynes into cyclic acetals and thioacetals with a gold(I) catalyst: comparison with Brønsted acid catalysts

Amino acids/peptides conjugated heterocycles: A tool for the recent development of novel therapeutic agents.

Vibrational spectroscopic studies, Fukui functions, HOMO-LUMO, NLO, NBO analysis and molecular docking study of (E)-1-(1,3-benzodioxol-5-yl)-4,4-dimethylpent-1-en-3-one, a potential precursor to bioactive agents

The increased incidence of opportunistic fungal infections, associated with greater resistance to the antifungal drugs currently in use has highlighted the need for new solutions. In this study twenty four coumarin derivatives were screened in vitro for antifungal activity against strains of Aspergillus. Some of the compounds exhibited significant antifungal activity with MICs values ranging between 16 and 32 µg/mL. The structure-activity relationships (SAR) study demonstrated that O-substitutions are essential for antifungal activity. It also showed that the presence of a short aliphatic chain and/or electron withdrawing groups (NO2 and/or acetate) favor activity. These findings were confirmed using density functional theory (DFT), when calculating the LUMO density. In Principal Component Analysis (PCA), two significant principal components (PCs) explained more than 60% of the total variance. The best Partial Least Squares Regression (PLS) model showed an r2 of 0.86 and q2cv of 0.64 corroborating the SAR observations as well as demonstrating a greater probe N1 interaction for active compounds. Descriptors generated by TIP correlogram demonstrated the importance of the molecular shape for antifungal activity.

https://www.mdpi.com/1422-0067/14/1/1293/pdf

Synthesis, structure-activity relationships (SAR) and in silico studies of coumarin derivatives with antifungal activity.

Synthesis, antitumour and antimicrobial activities of new peptidyl derivatives containing the 1,3-benzodioxole system

Synthesis, Antitumor and Antimicrobial Activities of New Peptidyl Derivatives Containing the 1,3‐Benzodioxole System.

The synthesis of the new amino-acyl derivatives starting from a 1.3-benzodioxole unit present in safrole is described. All the synthesised compounds, that could be conveniently prepared in a few steps process, have been characterised by the IR and the 'H-NMR Spectroscopy. Introduction The 1,3-benzodioxole moiety present in safrole, has shown interesting and diversified properties when used to obtain new biologically active drugs\". Safrole, an abundant natural product occurring as the principal chemical constituent of sassafraz oil (ocotea pretiosa, Benth). The 1,3-benzodioxole unit, can be identified in some clinical antitumor agents like, etoposide and teniposide. In 1983, the FDA reported that, safrole or sassafras, the extract or the oil, was an ingredient in 113 over-the-counter drug formulations, generally for topical application, but occasionally for oral administration. However the carcinogenic and other toxicological effects of this product have been pointed out'' For some time, the interest for the design of prodrug containing a peptidyl or an amino acid moiety has increased. The use of amino acid has been exploited for the development of new biologically and less toxic active compounds\"'. As part of a research program with the objective to synthesis of bioactive compounds, using abundant Brazilian natural products, we have thus developed a synthetic sequence dealing with the synthesis of the safrole derivatives which present an amino-acyl moiety in a side chain.

Synthesis of 1,3-benzodioxole derivatives containing a amino acid moiety in side chain

As part of a preliminary study on novel antitumor drugs, the synthesis of a new class of peptidyl compounds, using natural safrole is described The 1,3-benzodioxole group was initially converted into a 6-alyl-benzo[l,3]dioxole-5-ilamine. The peptidyl derivatives were prepared by condensation of amino moiety with appropriately protected α-amino acids. The structures of this new class of compounds was determined by IR and NMR spectral data. Introduction Safrole is an abundant Brazilian natural product from sassafraz oil (ocotea preliosa Mer., Lauraceae), which presents interesting functionality and chemical reactivity that suggests its use as an efficient and versatile natural syntonThe methvlenedioxy unit from safrole, has been identified in some clinical antitumor agents like etoposide and teniposide As part of a research program with the objective of synthesizing bioactive compounds by the use of abundant and inexpensive starting material, we have thus developed a synthetic sequence dealing with the synthesis of the safrole derivatives'* On the other hand, it has been identified some peptides that home specifically to tumor blood vessels' On this basis. It has been shown that therapeutically active agents linked to small peptides or amino acid residues, reduce toxicity and enhance their therapeutic effects\" It is supposed that an amino acid transport system in the cell can be exploited to deliver the active nucleus to target cells for the drug activity. Considering the potential of ring system from safrole we undertook the synthesis of peptidyl compounds 4a-h employing the coupling reagents used in peptide synthesis. This paper reports reports the strategy of synthesis of these new compounds and Vol. 7, No. 5, 2001 Synthesis ofpeptidyl benzodioxole derivatives from safrole, a potential class of antitumor drugs the verification of their structures by spectroscopic means. The compounds described herein constitute a set of potentially useful building blocks in the synthesis of modified peptides. Synthesis of the compounds Our synthetic strategy was based on the selective and classical nitration with nitric acid in acetic acid, on the 5 position on the 1,3-benzodioxole moiety The nitro group was reduced in mild conditions using iron powder and NH4CI in ethanol/water to afford the amino derivative. The peptidomimetic derivatives were synthesized from Boc-protected L-amino acids. The synthetic routes were applied on appropriately protected lipophilic (glycine, phenylalanine, alanine, valine, leucine) and basic (lysine) amino acids The amino group in side chain of lysine was protected by a fluorenylmethvloxycarbonil (Fmoc) group The expected peptidyl derivatives 4a-h have been synthesized by condensation with 6-allyl-benzo[l,3]dioxole-5-ilamine (3) with α-aminoacids using diciclohecylcarbodiimide (DCC) and hydroxybenzotriazole (HOBt) to activate the carboxylic acid function in order to generate an active ester in situ (Scheme I). The safrole derivatives were obtained at 25 to 95% yield Scheme 1 a CHj-Phe d (CH : ) r NH-Boc b CH2-CH(CH,)2 e CH3 c CHiCHĵ f Η (a) HNOJ,ACOHL (b) Fe.NHjClBOH H ^ rctluv (c) P-NH-CH(R)-COOH ; (d) DMF. 0\"C. DCC. HOBt: P= Boc: 4in;: P= Z: 4f The structure of 4a-f, was proved by IR and 'H-NMR spectral data. (Table I) The IR spectra showed a characteristic N-H stretching vibration around 3263 and 3363 cm-1, overlap C = 0 stretching, amide I band around 1649 and 1671 cm\"' Asymmetrical C-O-C stretching band around 1262 cm\"' and symmetrical streching near 1026 cm\"' The 'H-NMR spectra of compounds showed the same characteristic at (δ) 5.75-5 91 ppm attributed to methinic proton, at 4 97-4.99 and 5.03-5.05 ppm, corresponding to methilenic protons. Another representative signal occurred at 5.98 ppm and was attributed to the methylenedioxy group Two signals occurring between 6.70 and 6.74 ppm as two singlets indicating a typical para-aromatic hydrogen pattern. The NH linked to aromatic ring showed a singlet around 9.07 and 9.25 ppm. For the NH a characteristic dublet around 6.91-7.57 ppm has shown

Kezia Peixoto da Silva

Papers

Synthesis, antitumour and antimicrobial activities of new peptidyl derivatives containing the 1,3-benzodioxole system

Synthesis, Antitumor and Antimicrobial Activities of New Peptidyl Derivatives Containing the 1,3‐Benzodioxole System.

Synthesis of 1,3-benzodioxole derivatives containing a amino acid moiety in side chain

Synthesis of peptidyl benzodioxole derivatives from safrole, a potential class of antitumor drugs