A doubly stereocontrolled organocatalytic asymmetric Michael addition to the synthesis of substituted succinimides is described. Starting from aldehydes and maleimides, both enantiomers of the succinimides could be obtained in high to excellent yields (up to 98%) and enantioselectivities (up to 99%) when one of the two special chiral diterpene-derived bifunctional thioureas was individually used as a catalyst. Moreover, these catalysts can be efficiently used in large-scale catalytic synthesis with the same level of yield and enantioselectivity. Chirality 00:000–000, 2014. © 2014 Wiley Periodicals, Inc.

Pyrazoles are an important class of molecular structures with significant biological and pharmaceutical activities. Herein, heterocyclic compounds containing both a pyrazole motif and a masked amino acid structure are synthesized through the asymmetric Michael/aromatization of azlactones to α,β-unsaturated pyrazolones by using isosteviol-derived amine thiourea as the organocatalyst. The products are obtained in good yields (up to 93 %) with good diastereoselectivities and good enantioselectivities (up to >10:1 dr, 97 % ee).

An approach based on combinations of various water compatible Lewis acids and lipophilic group containing amphiphilic prolinamide co-catalysts has been evaluated for the direct asymmetric Aldol reaction. From the broad screening of chloride salts from alkali metal to transition metal, LiCl, ZnCl₂ and SnCl₂ lead to the highest stereoselectivities. The optimized catalytic conditions (10 mol% prolinamide with 10 mol% MCl₂ or 20 mol% LiCl at room temperature on water) gave anti-products with improved enantioselectivities (up to 99% ee) compared to the moderately stereoselective procedure based on prolinamide activation only.

(R)-1,1′-Binaphthyl-2,2′-diol (R-BINOL) derived chiral phosphoric acids have been explored as organocatalysts for the asymmetric oxidation of a series of aryl alkyl sulfides and 1,3-dithianes derived from aldehydes with aqueous hydrogen peroxide (H₂O₂) as the terminal oxidant. The enantiomerically enriched sulfoxides are obtained in moderate to excellent yield (up to 99%) with excellent diastereoselectivity (up to >99:1 dr) and moderate to good enantioselectivity (up to 91:9 er). In particular, the present protocol stereoselectively provides an efficient access to enantiomerically enriched aryl alkyl sulfoxides and dithioacetal mono-sulfoxides, which strictly restrains the formation of the undesirable by-products: sulfones or disulfoxides. The tracking experiments also verify that this approach proceeds via a direct sulfoxidation process, instead of a kinetic resolution route by overoxidation of the resulting sulfoxides.

Heterocyclic spirooxindoles that bear a multisubstitutedheterocyclic motif and quaternary stereocenter at the 3-position are prevalent in a large number of spirooxindole alkaloids, which are pharmaceutically relevant compounds with remarkable biological activities. In this paper, we report an efficient method for the construction of enantiomerically enriched spiro[2H-pyran-3,4′-indoline] derivatives by a systematic Michael/reduction/cyclization sequence. The initial Michael addition of isatylidenemalononitriles with ketones was catalyzed by a cinchona-based chiral primary amine and L-camphorsulfonic acid and furnished multifunctional, optically active Michael adducts in high yields (81–99 %) with excellent enantioselectivities (95 to >99 % ee). Subsequently, the Michael adducts were converted into spiro[2H-pyran-3,4′-indoline] derivatives in 52–93 % yields with 1.5:1 to 20:1 diastereomeric ratio and 90–99 % ee by utilizing NaBH₄ as a cascade reduction/cyclization reagent.

In this work, six isosteviolamino acid conjugates were designed and synthesized through simple condensation on a large scale without protecting group (Scheme). These amphiphilic organocatalysts mediated asymmetric three-component Mannich reactions of cyclohexanone and anilines with aromatic aldehydes in the presence of H₂O. Meanwhile, the isosteviolproline conjugate 3b has been established as a highly efficient catalyst (Table 1), and afforded syn-Mannich products with excellent diastereoselectivities (syn/anti up to 98 : 2) and enantioselectivities (up to >99% ee; Table 3). The transition state of the reaction in the presence of H₂O is proposed (Fig. 2).

A novel class of chiral amphiphilic bifunctional thioureas based on a beyerane scaffold and each containing a primary amino group were designed and synthesized from the readily available natural product isosteviol. The thioureas were shown to be effective for catalyzing asymmetric Michael additions between isobutyraldehyde and nitroalkenes. The chiral thiourea 1a furnished S enantiomers, whereas 1b afforded R enantiomers, both with high yields (up to 92 %) and high to excellent enantioselectivities (up to 98 %). Furthermore, the reactions proceeded smoothly both in organic solvents and in water under mild conditions.

Isosteviol-amino acid conjugates were synthesized and used as chiral catalysts for the asymmetric three-component Mannich reaction with hydroxyacetone as donor molecule. Good yields (up to 98%) and excellent stereoselectivities (up to 97:3 dr and 99% ee) were achieved in a short reaction time. In addition, syn- or anti-configurations of α-hydroxy-β-amino carbonyl compounds were obtained as main products with different chiral catalysts.

A series of new polymer-supported palladium complexes with C,N-ligands (1a–e and 2a–c) were easily synthesized. The synthesized catalysts could be applied as efficient heterogeneous catalysts for the Heck coupling reaction (turnover frequency up to 12 600 h⁻¹). Additionally, the catalysts could be recovered by a simple filtration progress and could be reused for at least five times with a slow progressive decrease in activity. Copyright © 2010 John Wiley & Sons, Ltd.

Some efficient polymer-supported palladium catalysts have been synthesized. Their catalytic effects were evaluated in the Heck reaction of iodobenzene with acrylates or styrene. High catalytic activities were achieved with turn over frequencies (TOF) up to 28000 and 6250, respectively. For the reaction of iodobenzene with styrene, high stereoselectivity was obtained. Additionally, the catalysts could be recovered by a simple filtration progress and can be reused for at least 5 times with a slow progressive decrease in activity.

Considerable interests have been attracted by isosteviol and its derivatives because of their large variety of bioactivities. In this project, a series of novel 15- and 16-substituted isosteviol derivatives were stereoselectively prepared by means of functional interconversions in ring D of the tetracyclic diterpene isosteviol. All compounds synthesized were characterized by analysis of NMR, IR, HR-MS data, and the configurations of 33 and 37 were confirmed by X-ray crystallographic analysis. The antibacterial activities in vitro of these isosteviol derivatives were investigated; the synthetic compounds were more active against Gram-positive than Gram-negative bacteria, and were especially active against Bacillus subtilis. Among them, compound 27 (MIC=1.56 μg/ml) exhibited the highest antibacterial activity and thus may be exploitable as a lead compound for the development of potent antibacterial agents.

A novel series of 3-membered ring fluorouracil conjugates including cyclopropylmethyl fluorouracil and (2,3-epoxypropyl) fluorouracil conjugates were synthesized via selective protection, and their structures were confirmed by IR, ¹H NMR and HRMS. Cytotoxicities in vitro of these conjugates were evaluated. Compounds 7, 8, 12 and 13 have shown cytotoxicities against Ec9706 cells in different degrees.