Search

The reaction of homophthalic anhydride with 1H-indol-3-carbaldimines was used for the preparation of trans- and cis-2-alkyl-3-indolyl-1-oxotetrahydroisoquinolin-4-carboxylic acids 3a–d. The stereochemistry of the reaction was investigated by means of 1H NMR spectroscopy. The carboxylic group of trans-3a–d was transformed stereoselectively via 4-hydroxymethyltetrahydroisoquinolin-1-ones into 4-(phthalimidomethyl)-derivatives trans-6a,b and 4-(imidazolylmethyl)-derivatives trans-8b–d. Compounds trans-6a,b and 8b–d were tested for antiaromatase activity, and the preliminary results showed that the phthalimidomethylisoquinolinone trans-6b at 50 μM concentration decreased the aromatase enzyme activity with 40%.

Therapeutically relevant proteins such as GPCRs, antibodies and kinases face clear limitations in NMR studies due to the challenges in site‐specific isotope labeling and deuteration in eukaryotic expression systems. Here we describe an efficient and simple method to observe the methyl groups of leucine residues in proteins expressed in bacterial, eukaryotic or cell‐free expression systems without modification of the expression protocol. The method relies on simple stereo‐selective 13C‐labeling and deuteration of leucine that alleviates the need for additional deuteration of the protein. The spectroscopic benefits of “local” deuteration are examined in detail through Forbidden Coherence Transfer (FCT) experiments and simulations. The utility of this labeling method is demonstrated in the cell‐free synthesis of bacteriorhodopsin and in the insect‐cell expression of the RRM2 domain of human RBM39., Methyl‐based magnetization usage can strongly benefit investigations of large protein systems via NMR spectroscopy. Here, a simple and cost‐effective method to obtain locally deuterated leucine suitable for methyl NMR and to quantify its benefits is presented. The approach substantially expands the applicability of methyl labeling in emerging expression systems including cell‐free and eukaryotic systems.

A novel green method was developed for the preparation of a squaraine dye, on an 8-mmol scale, by microwave irradiation of two equivalents of 1,3,3-trimethyl-2-methyleneindoline with one equivalent squaric acid in the green solvent, ethyl l-lactate. The time required for this green synthesis is only 4 min. The target squaraine dye was isolated in excellent yield (81%) and with high purity.

Substituted (±)-trans-1-benzyl-6-oxo-2-phenylpiperidine-3-carboxamides (type I) and the acylated derivatives of (±)-trans-5-amino-1-benzyl-6-phenylpiperidin-2-one (type II) were prepared by the reaction of (±)-trans-1-benzyl-6-oxo-2-phenylpiperidine-3-carboxylic acid and some common reagents to provide the products in satisfactory yields. Newly synthesized compounds share the same moiety with common SP antagonists and thus similar activities might be expected.

The reaction of succinic anhydride and N-benzylidene-benzylamine gave rise to the corresponding substituted trans-5-oxopyrrolidine-3-carboxylic acid, which was transformed stereoselectively into two series of compounds. The first one consists of carboxamides, and the second one includes aminomethyl derivatives. The compounds prepared incorporate both a pyrrolidinone part and other nitrogen containing heterocyclic fragments of pharmacological interest.

A series of trans- and cis-3,4-disubstituted 5-oxomorpholine-2-carboxylic acids 5 were prepared by a cyclocondensation between diglycolic anhydride 3 and arylideneamines 4. Transformations of the carboxylic group leading to a peptide bond in the side chain to the morpholinone ring were effected. The relative configurations and the preferred conformations of the substituents at the morpholinone ring in some of the newly prepared derivatives were determined by means of 1H NMR and X-ray analysis.