Synthesis of spiropyridazine-benzosultams by the [4 + 2] annulation reaction of 3-substituted benzoisothiazole 1,1-dioxides with 1,2-diaza-1,3-dienes.

A simple and efficient method for the synthesis of spiropyridazine-benzosultams has been developed by means of [4 + 2] annulation reaction of 3-substituted benzoisothiazole 1,1-dioxides with 1,2-diaza-1,3-dienes. This approach displays advantages such as mild reaction conditions, wide substrate range tolerance, simple operation, compatibility with gram-scale preparation.

Silver Catalyzed Site-Selective C(sp3)-H Bond Amination of Secondary over Primary C(sp3)-H Bonds.

Sulfamates are widespread in numerous pharmacologically active molecules. In this paper, Silver/Bathophenanthroline catalyzed the intramolecular selective amination of primary C(sp3)-H bonds and secondary C(sp3)-H bonds of sulfamate esters, to produce cyclic sulfamates in good yields and with a high site-selectivity. DFT calculations revealed that the interaction between sulfamates and L10 makes the molecule more firmly attached to the catalyst, benefiting the catalysis reaction. The in vitro anticancer activity of the final products was evaluated in MCF-7 breast cancer cells.

Late-Stage Intermolecular Allylic C-H Amination.

Allylic amination enables late-stage functionalization of natural products where allylic C-H bonds are abundant and introduction of nitrogen may alter biological profiles. Despite advances, intermolecular allylic amination remains a challenging problem due to reactivity and selectivity issues that often mandate excess substrate, furnish product mixtures, and render important classes of olefins (for example, functionalized cyclic) not viable substrates. Here we report that a sustainable manganese perchlorophthalocyanine catalyst, [MnIII(ClPc)], achieves selective, preparative intermolecular allylic C-H amination of 32 cyclic and linear compounds, including ones housing basic amines and competing sites for allylic, ethereal, and benzylic amination. Mechanistic studies support that the high selectivity of [MnIII(ClPc)] may be attributed to its electrophilic, bulky nature and stepwise amination mechanism. Late-stage amination is demonstrated on five distinct classes of natural products, generally with >20:1 site-, regio-, and diastereoselectivity.

Spiro Indane-Based Phosphine-Oxazolines as Highly Efficient P,N Ligands for Enantioselective Pd-Catalyzed Allylic Alkylation of Indoles and Allylic Etherification.

A series of indane-based phosphine-oxazoline ligands with a spirocarbon stereogenic center were examined for palladium-catalyzed asymmetric allylic alkylation of indoles. Under optimized conditions, high yields (up to 98%) and enantioselectivities (up to 98% ee) were obtained with a broad scope of indole derivatives. The ligand was determined to be the most efficient P,N-ligand for this reaction. Moreover, the ligand was also efficient for Pd-catalyzed asymmetric allylic etherification with hard aliphatic alcohols as nucleophiles.

Synthesis of highly rigid phosphine-oxazoline ligands for palladium-catalyzed asymmetric allylic alkylation.

A highly rigid spiro phosphine-oxazoline ligand skeleton with a spirocarbon stereogenic center was developed from 7-bromo-1-indanone. The catalytic performance of the ligand was demonstrated in palladium-catalyzed asymmetric allylic alkylation. Under optimized conditions, high yields (up to 99%) and enantioselectivities (up to 99.9% ee) were obtained for reactions of 1,3-diphenylallyl acetates and symmetrical 1,3-dicarbonyl substrates.

Synthetic Strategy and Anti-Tumor Activities of Macrocyclic Scaffolds Based on 4-Hydroxyproline.

A series of novel 13- to 15-member hydroxyproline-based macrocycles, which contain alkyl-alkyl ether and alkyl-aryl ether moieties, have been synthesized by the strategy of macrocyclization utilising azide-alkyne cycloaddition, Mitsunobu protocol and amide formation. Their anti-tumor activities towards A549, MDA-MB-231 and Hep G2 cells were screened in vitro by an MTT assay. The results indicated that 13-member macrocycle 33 containing alkene chain showed the best results, exhibiting the highest inhibitory effects towards lung cancer cell line A549, which was higher than that of the reference cisplatin (IC50 value = 2.55 µmol/L).

Efficient Production of Lactic Acid from Sweet Sorghum Juice by a Newly Isolated Lactobacillus salivarius CGMCC 7.75.

Sweet sorghum juice was a cheap and renewable resource, and also a potential carbon source for the fermentation production of lactic acid (LA) by a lactic acid bacterium. One newly isolated strain Lactobacillus salivarius CGMCC 7.75 showed the ability to produce the highest yield and optical purity of LA from sweet sorghum juice. Studies of feeding different concentrations of sweet sorghum juice and nitrogen source suggested the optimal concentrations of fermentation were 325 ml l(-1) and 20 g l(-1), respectively. This combination produced 142.49 g l(-1) LA with a productivity level of 0.90 g of LA per gram of sugars consumed. The results indicated the high LA concentration achieved using L. salivarius CGMCC 7.75 not only gives cheap industrial product, but also broaden the application of sweet sorghum.

Nickel-catalysed cross-electrophile coupling of aryl bromides and primary alkyl bromides.

The structure of primary alkylated arenes plays an important role in the molecular action of drugs and natural products. The nickel/spiro-bidentate-pyox catalysed cross-electrophile coupling of aryl bromides and primary alkyl bromides was developed for the formation of the Csp2-Csp3 bond, which provided an efficient method for the synthesis of primary alkylated arenes. The reactions could tolerate functional groups such as ester, aldehyde, ketone, ether, benzyl, and imide.

Studies toward the synthesis of phomactin A. An approach to the macrocyclic core.

An approach to the macrocyclic core of phomactin A is described. Central to this strategy is the use of a cis-fused oxadecalin intermediate, prepared using the dihydropyrone Diels-Alder reaction. The conformational bias inherent to this system is then used to facilitate macrocycle formation via an intramolecular B-alkyl Suzuki coupling.

An efficient synthesis of a spirocyclic oxindole analogue.

An efficient, scaleable synthesis approach towards the spirocyclic oxindole analogue 1'-(tert-butoxycarbonyl)-2-oxospiro[indoline-3,4'-piperidine]-5-carboxylic acid (1) is described. The key steps are dianion alkylation and cyclization of ethyl 2- oxindoline-5-carboxylate (4) and demethylation of the resulting spirocyclic oxindole ethyl 1'-methyl-2-oxospiro[indoline-3,4'-piperidine]-5-carboxylate (5). The target compound was obtained in an overall yield of 35 % over eight steps without resorting to chromatographic purification.

Total synthesis of the ethyl ester of the major urinary metabolite of prostaglandin E(2).

The preparation of the ethyl ester of the major urinary metabolite of prostaglandin E(2) 3 is described. The key step is the kinetic opening of the TBS-protected bicyclic ketone 7 with thiophenol.