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The first enantioselective reduction of 2‐substituted cyclic imines to the corresponding amines (pyrrolidines, piperidines, and azepines) by imine reductases (IREDs) in non‐conventional solvents is reported. The best results were obtained in a glycerol/phosphate buffer 1 : 1 mixture, in which heterocyclic amines were produced with full conversions (>99 %), moderate to good yields (22–84 %) and excellent S‐enantioselectivities (up to >99 % ee). Remarkably, the process can be performed at a 100 mM substrate loading, which, for the model compound, means a concentration of 14.5 g L−1. A fed‐batch protocol was also developed for a convenient scale‐up transformation, and one millimole of substrate 1 a was readily converted into 120 mg of enantiopure amine (S)‐2 a with a remarkable 80 % overall yield. This aspect strongly contributes to making the process potentially attractive for large‐scale applications in terms of economic and environmental sustainability for a good number of substrates used to produce enantiopure cyclic amines of high pharmaceutical interest. [ABSTRACT FROM AUTHOR]

Pd-catalyzed aminocarbonylation in the presence of Xantphos as a ligand was used to transform lactam-, lactone-, and thiolactone-derived triflates into N-methoxy-N-methyl or morpholine Weinreb amides. The method could also be applied to synthesize dienones in which one of the double bonds is embedded in a heterocyclic moiety, as useful substrates for Nazarov cyclization.

A study on the conversion of lactum-derived vinyl triflates and phosphates into the corresponding vinyl boronates was carried out. It was concluded that delta-valero-lactam-derived vinyl triflates could be converted into the corresponding tetrahydropyridine-2-boronic acid pinacol ester derivatives, which results in an umpolung.

Three different procedures are compared to obtain properly substituted divinyl ketones in which one of the double bonds is embedded in a five-membered heterocyclic structure and therefore suitable to produce cyclopenta-fused pyrrole, derivatives by the acid-catalyzed Nazarov reaction. A convergent procedure base on the umpolung to a vinylstannane gave acceptable yields of the divinyl ketone, which forms a key intermediate in the synthesis of roseophilin.

Reporting on the torquoselectivity in the cyclization of 2-substituted five-membered azacycle and 2- and 4-substituted six-membered oxacycle derivatives. The reaction is highly diastereoselective with 2-substituted five-membered lactam derivatives 11a and 11b and leads to cis disubstituted cyclopenta-fused pyrrolines 13a and 13b, respectively.

Research has been conducted on the dipeptide isosteres produced by L-leucine and meso-tartaric acid derivatives. The isosteres have been inserted into a small peptide and the conformational features of the resulting peptides have been studied via IR, NMR and molecular modeling methods revealing the presence of the reverse turn conformation in all the structures.

The Pd(0)-catalyzed reaction of vinyl triflates from six- and seven-membered N-alkoxycarbonyl lactams with aryl-, alkenyl-, allyl- and alkylboronic acids or their esters has been carried out. The results of this reaction are discussed.

The synthesis of novel dipeptide isosteres containing the 3-aza-6,8-dioxabicyclo[3.2.1]octane-7carboxylic acid structure (BTAa) is described. The method can be used on natural, unnatural and unusual amino acids and all stereocenters can be controlled by selection of the appropriate starting precursors.

The feasibility of synthesizing 19-nor-10-azasteroid that has a 17-(3-pyridyl) constituent has been demonstrated. The compound is a class of 5alpha-reductase enzyme inhibitors that are capable of converting testosterone into androgen dihydrotestosterone, a more potent form of the male hormone. 19-nor-10-azasteroid's inhibiting effect on human cytochrome P45017alpha is seen as one of the promising treatment for prostate cancer.

A four-step process for the preparation of enantiomerically pure 3,5-diarylpyrrolizidines has been developed resulting in overall yields in the range of 41% to 56%. The new process was based on a double nucleophilic displacement that occurs in chiral 1,7-diaryl-4-[(N-benzyl)amino]heptane-1,7-diols at the conversion of the two hydroxy groups into mesylates. The methodology is of great interest because of the important biological attributes displayed by pyrrolizidine alkaloids.

Thermal rearrangement and ring closure characterize the one-step synthesis of 5, 6-dihydro-7(8H)-indolizinones and 2,3,5,6-tetrahydro-7(1H)-indolizinones from isoxazoline-5-spirocyclopropanes. This rapid, mild, regioselective and stereoselective process involves the sequential cleavage of the isoxazoline N-O bond and of the cyclopropyl ring. When the substrate has a fused cyclohexane or an attached cyclohexanone, the product is a tricycle with an N-bridgehead. The presence of substituents on the side chain accelerates the reaction.

A stereodivergent strategy to obtain enantiopure cis and trans 4‐aminopipecolic acids (4‐APAs) in a suitably protected form for peptide synthesis has been devised starting from a common, known precursor in turn easily prepared from commercial (R)‐4‐cyano‐3‐hydroxybutyric acid ethyl ester. The two isomers were efficiently obtained in 40 % and 23 % overall yields, respectively, in seven and ten steps. To demonstrate their usefulness in peptidomimetic synthesis, both 4‐APA isomers were incorporated as γ‐amino acids in a cyclic RGD‐containing sequence, although for the trans 4‐APA isomer a further amino acid in the sequence (L‐Phe) was needed to allow ring closure. The two cyclopeptides were tested as αVβ3 integrin antagonists in comparison with cilengitide. [ABSTRACT FROM AUTHOR]

The gold(I)‐catalysed cyclization of N‐tosyl‐protected 5‐benzyl‐6‐((trimethylsilyl)ethynyl)‐1,2,3,4‐tetrahydropyridines, prepared by the Sonogashira coupling of lactam‐derived enol triflates, provides tetrahydrobenzo[g]quinolines whose skeleton represents a recurrent motif in natural compounds. The Au(I)‐catalysed reaction is carried out with (C6F5)3PAuCl/AgNTf2 as the catalyst system and proceeds via a 6‐exo‐dig cyclization to form an exocyclic double bond, which eventually isomerises to the aromatic tetrahydrobenzo[g]quinoline. The mode of cyclization is discussed and supported by DFT calculations. [ABSTRACT FROM AUTHOR]