Camilla Parmeggiani

Transition metal based catalysts in the aerobic oxidation of alcohols

The oxidation of alcohols to the corresponding carbonyl compounds is a pivotal reaction in organic synthesis. However, traditional oxidants are often toxic and release considerable amounts of by-products. As an alternative, oxygen (or even better air) is among the cheaper and less polluting stoichiometric oxidants, since it produces no waste or water as the sole by-product. The implementation of a transition metal-based catalyst in combination with oxygen represents an emerging alternative to the traditional procedures. This review aims to give an overview on the most important advances made by the scientific community in the last 15 years in the field of aerobic oxidations of alcohols catalyzed by transition metals in the form of homogeneous catalysts, heterogeneous catalysts and, more recently, nanoparticles.

Light‐Fueled Microscopic Walkers

The first microscopic artificial walker equipped with liquid-crystalline elastomer muscle is reported. The walker is fabricated by direct laser writing, is smaller than any known living terrestrial creatures, and is capable of several autonomous locomotions on different surfaces.

Total syntheses of casuarine and its 6-O-alpha-glucoside: complementary inhibition towards glycoside hydrolases of the GH31 and GH37 families

Total synthesis of naturally occurring casuarine (1) and the first total synthesis of casuarine 6-O-alpha-glucoside (2) were achieved through complete stereoselective nitrone cycloaddition, Tamao-Fleming oxidation and selective alpha-glucosylation as key steps. Biological assays of the two compounds proved their strong and selective inhibitory properties towards glucoamylase NtMGAM and trehalase Tre37A, respectively, which place them among the most powerful inhibitors of these enzymes. The structural determination of the complexes of NtMGAM with 1 and of Tre37A with 2 revealed interesting similarities in the catalytic sites of these two enzymes which belong to different families and clans.

High‐Resolution 3D Direct Laser Writing for Liquid‐Crystalline Elastomer Microstructures

The paper describes 3D structures made of liquid-crystalline elastomer (LCE) - rings, woodpiles, etc. - fabricated by two-photon absorption direct laser writing with sub-micrometer resolution while maintaining the desired molecular orientation. These results lay the foundations for creating 3D, micrometer-sized, light-controlled LCE structures.

Stereocomplementary Routes to Hydroxylated Nitrogen Heterocycles: Total Syntheses of Casuarine, Australine, and 7‐epi‐Australine

Addition of lithiated 1-benzyloxyallene to a D-arabinose-derived cyclic nitrone occurred with perfect diastereoselectivity furnishing a bicyclic 1,2-oxazine derivative, which is an excellent precursor for pyrrolizidine alkaloids hydroxylated at C-7 with optional configuration at this stereogenic center. Depending on the stage of the N-O bond cleavage and ring re-closure, 7-hydroxypyrrolizidines with 7R or 7S configuration were obtained, as a result of completely selective addition reactions occurring complementarily at the bottom or top face of the endocyclic C-C double bond in six- and five-membered B rings, respectively. Applicability of these stereodivergent routes to obtain polyhydroxy pyrrolizidine alkaloids is demonstrated by the efficient syntheses of casuarine and australine as examples of the two classes of diversely configured 7-hydroxypyrrolizidine alkaloids. An alternative synthesis of australine and two strategies for the preparation of 7-epi-australine are also reported, which demonstrate that the stereoselectivity of hydride reduction of an exocyclic C-O double bond is independent of the ring size, occurring preferentially from the top face either in a six- or five-membered ring.

Casuarine-6-O-α-D-glucoside and its analogues are tight binding inhibitors of insect and bacterial trehalases

Two novel casuarine-6-alpha-D-glucoside analogues, as well as the parent compound, were synthesized and tested as inhibitors towards Chironomus riparius, mammalian pig kidney and Escherichia coli trehalases. Their potent and selective activity is promising for the development of new insecticides.

Alignment engineering in liquid crystalline elastomers: Free-form microstructures with multiple functionalities

We report a method to fabricate polymer microstructures with local control over the molecular orientation. Alignment control is achieved on molecular level in a structure of arbitrary form that can be from 1 to 100 μm in size, by fixing the local boundary conditions with micro-grating patterns. The method makes use of two-photon polymerization (Direct Laser Writing) and is demonstrated specifically in liquid-crystalline elastomers. This concept allows for the realization of free-form polymeric structures with multiple functionalities which are not possible to realize with existing techniques and which can be locally controlled by light in the micrometer scale.

A step forward towards sustainable aerobic alcohol oxidation: new and revised catalysts based on transition metals on solid supports

The oxidation of alcohols is a reaction under continuous investigation, due to the importance of oxidation products and the necessity to perform it in a more sustainable way with respect to traditional procedures. In particular, the combination of a metal catalyst with molecular oxygen or air represents one of the best alternatives in this field. New catalysts are continuously proposed in the literature, and it is not often easy to compare their performances owing to the great amount of examples reported. Heterogeneous catalysts represent the best solution to heavy metal contamination of the products, provided that leaching has not occurred. Moreover, they ideally should be recovered without deactivation and reused after reaction. The employment of air or oxygen in non-flammable solvents (ideally, water) is also highly appreciated, for safety reasons. We have tried in this review to focus on some very recent reports on solid supported transition metal catalysts that strive to follow these principles thus performing oxidation in a more sustainable way while guaranteeing an acceptable substrate scope for synthetic utility.

Total Synthesis of (−)-Uniflorine A⊥

Total synthesis of (-)-uniflorine A (3) has been accomplished in nine steps and 11% overall yield from carbohydrate-based nitrone 5. The key steps of the synthetic strategy were a high regio- and complete stereoselective 1,3-dipolar cycloaddition of alkene 6 with nitrone 5, a Tamao-Fleming reaction for replacing the silicon substituent with a hydroxy group with retention of configuration, and a Mitsunobu reaction to establish the correct configuration of the target molecule at C-6.

A membrane-bound trehalase from Chironomus riparius larvae: purification and sensitivity to inhibition

A preparation of a membrane-bound trehalase from the larvae of the midge Chironomus riparius (Diptera: Chironomidae) was obtained by detergent solubilization, ion-exchange chromatography and concanavalin A affinity chromatography. Trehalase was purified 1080-fold to a specific activity of 75 U mg(-)(1). The initial rate of trehalase activity followed Henri-Michaelis-Menten kinetics with a K(m) of 0.48 +/- 0.04 mM. Catalytic efficiency was maximal at pH 6.5. The activity was highly inhibited by mono- and bicyclic iminosugar alkaloids such as (in order of potency) casuarine (IC(50) = 0.25 +/- 0.03 microM), deoxynojirimycin (IC(50) = 2.83 +/- 0.34 microM) and castanospermine (IC(50) = 12.7 +/- 1.4 microM). Increasing substrate concentration reduced the inhibition. However, in the presence of deoxynojirimycin, Lineweaver-Burk plots were curvilinear upward. Linear plots were obtained with porcine trehalase. Here, we propose that deoxynojirimycin inhibits the activity of trehalase from C. riparius according to a ligand exclusion model. Inhibition was further characterized by measuring enzyme activity in the presence of a series of casuarine and deoxynojirimycin derivatives. For comparison, inhibition studies were also performed with porcine trehalase. Results indicate substantial differences between midge trehalase and mammalian trehalase suggesting that, in principle, inhibitors against insect pests having trehalase as biochemical targets can be developed.