A new efficient route to chiral 1,3-disubstituted ferrocenes: application to the syntheses of (R(p))- and (S(p))-17alpha-[(3'-formylferrocenyl)ethynyl]estradiol

Starting from (2S,4S)-2-ferrocenyl-4-(methoxymethyl)-1,3-dioxane (4), use of the stereogenic ortho-directing menthyl para-tolyl sulfoxide group, which occupies the 2' position in the ferrocenyl ring and redirects subsequent lithiation to the 3' position, allowed the synthesis of optically pure (S(p))-1-formyl-3-iodoferrocene (8), that was characterized by single-crystal X-ray diffraction. Combination of this method with a protection-deprotection strategy, using trimethylsilyl as a temporary blocking group, yielded (R(p))-1-formyl-3-iodoferrocene (13). Separate Sonogashira coupling of each of the enantiomeric iodoformylferrocenes 8 and 13 with 17alpha-ethynyl-estradiol produced (R(p))-17alpha-[(3'-formylferrocenyl)ethynyl]estradiol (14) and (S(p))-17alpha-[(3'-formylferrocenyl)ethynyl]estradiol (15), respectively.     

Stereoselective biocatalytic synthesis of (S)-2-hydroxy-2-methylbutyric acid via substrate engineering by using "thio-disguised" precursors and oxynitrilase catalysis

3-Tetrahydrothiophenone (4) and 4-phenylthiobutan-2-one (7) were used as masked 2-butanone equivalents to give the corresponding cyanohydrins 5 (79 % yield, 91 % ee) and 8 (95 % yield, 96 % ee) in an enzymatic cyanohydrin reaction applying the hydroxynitrile lyase (HNL) from Hevea brasiliensis. After hydrolysis and desulphurisation the desired intermediate (S)-2-hydroxy-2-methylbutyric acid (10) was obtained with 99 % ee. Interestingly, when applying (R)-selective HNL from Prunus amygdalus again the (S)-cyanohydrin 5 was formed (62 % ee). The absolute configuration of 5 was verified by crystal structure determination of the corresponding hydrolysis derived carboxylate. The fact that both enzymes yield the same enantiomer was analysed and interpreted by molecular modelling calculations.     

Bioorganometallic Chemistry with IspG and IspH: Structure,Function, and Inhibition of the [Fe4S4] Proteins Involved in Isoprenoid Biosynthesis

Enzymes of the methylerythritol phosphate pathway of isoprenoid biosynthesis are attractive anti‐infective drug targets. The last two enzymes of this pathway, IspG and IspH, are [Fe₄S₄] proteins that are not produced by humans and catalyze 2 H⁺/ 2 e^? reductions with novel mechanisms. In this Review, we summarize recent advances in structural, mechanistic, and inhibitory studies of these two enzymes. In particular, mechanistic proposals involving bioorganometallic intermediates are presented, and compared with other mechanistic possibilities. In addition, inhibitors based on substrate analogues as well as developed by rational design and compound‐library screening, are discussed. The results presented support bioorganometallic catalytic mechanisms for IspG and IspH, and open up new routes to anti‐infective drug design targeting [Fe₄S₄] clusters in proteins.     

Fractional crystallisation of (±)-iso-amarine with mandelic acid: convenient access to (R,R)- and (S,S)-1,2-diamino-1,2-diphenylethanes

(±)-iso-Amarine can be conveniently resolved via 1:1 salt formation with either hand of mandelic acid. Enantiopure iso-amarine can be acetylated and hydrolysed to give enantiopure 1,2-diamino-1,2-diphenylethanes.     

Stereoselective synthesis of protected (2R,3R,4S)-4,7-diamino-2,3-dihydroxyheptanoic acid: a novel amino acid of callipeltins A and D

An orthogonally protected derivative 1 of (2R,3R,4S)-4,7-diamino-2,3-dihydroxyheptanoic acid, the unusual amino acid residue of the biologically active marine peptides such as callipeltins A and D and neamphamide A, was efficiently prepared in 10 steps and 30% overall yield from a commercially available L-ornithine derivative 2. The key step includes the N-diphenylmethylene-controlled diastereoselective dihydroxylation of (Z)-ester 3 with >13:1 selectivity for the desired isomer.     

A flexible approach to (S)-5-alkyl tetramic acid derivatives: application to the asymmetric synthesis of (+)-preussin and protected (3S,4S)-AHPPA

[reaction: see text] A flexible asymmetric approach to 5-alkyl tetramic acid derivatives is described, which is based on the use of 9 as the first synthetic equivalent to chiral nonracemic tetramic acid 5-carbanionic synthon 9b. The existence of the carbanion intermediate 9b was proven by trapping with trimethylchlorosilane. Application of the present method to the synthesis of antifungal alkaloid (+)-preussin, as well as protected (3S,4S)-AHPPA 6, is also described.     

Copper(II) complex with 6-(3,5-dimethyl-1H-pyrazol-1-yl)-2-(pyridin-2-yl)pyrimidin-4-amine: synthesis,crystal structure,and electronic spectroscopy

A copper(II) complex with 6-(3,5-dimethyl-1H-pyrazol-1-yl)-2-(pyridin-2-yl)pyrimidin-4-amine (L), [CuLCl₂], has been synthesized. This compound is formed irrespective of the Cu?:?L molar ratio (Cu?:?L?=?1?:?1, 2?:?1, and 20?:?1) in the MeOH/H₂O/DMF mixture as a single product. ESI-MS data demonstrate that the additional amount of CuCl₂ above the Cu?:?L?=?1?:?1 molar ratio, is effectively solvated, and high-nuclearity species are formed in trace amounts in the solution. The complex adopts a distorted square-pyramidal geometry with two chlorides and three nitrogen atoms from L. The electronic spectrum of the complex contains a broad band with a maximum at 12,820?cm^?1 within the region characteristic for square-pyramidal chromophores CuA₅ (A?=?Cl, N). Due to Cu?···?Cl contacts, the molecules of [CuLCl₂] form the dinuclear [CuLCl₂]₂ unit. Surprisingly, the NH₂-group participates in the formation of NH?···?Cl hydrogen bonds instead of the formation of (NH?···?N3_(pyrimidine))₂ synthon, which is common for N-heteroaromatic compounds containing the NH₂-group in the α-position to aza-atom. These hydrogen bonds together with Cu?···?Cl contacts result in the formation of a 3-D-structure.     

A Series of Green Oxovanadium(IV) Precatalysts with O,N and S Donor Ligands in a Sustainable Olefins Oligomerization Process

Designing catalyst systems based on transition metal ions and activators using the principles of green chemistry is a fundamental research goal of scientists due to the reduction of poisonous solvents, metal salts and organic ligands released into the environment. Urgent measures to reduce climate change are in line with the goals of sustainable development and the new restrictive laws ordained by the European Union. In this report, we attempted to use known oxovanadium(IV) green complex compounds with O, N and S donor ligands, i.e., [VO(TDA)phen] • 1.5 H₂O (TDA = thiodiacetate), (phen = 1,10-phenanthroline), oxovanadium(IV) microclusters with 2-phenylpyridine (oxovanadium(IV) cage), [VOO(dipic)(2-phepyH)] • H₂O (dipic = pyridine-2,6-dicarboxylate anion), (2-phepyH = 2-phenylpyridine), [VO(dipic)(dmbipy)] • 2H₂O (dmbipy = 4,4′-dimethoxy-2,2′-dipyridyl) and [VO(ODA)(bipy)] • 2 H₂O (ODA = oxydiacetate), (bipy = 2,2′-bipyridine), as precatalysts in oligomerization reactions of 3-buten-2-ol, 2-propen-1-ol, 2-chloro-2-propen-1-ol and 2,3-dibromo-2-propen-1-ol. The precatalysts, in most cases, turned out to be highly active because the catalytic activity exceeded 1000 g mmol⁻¹·h⁻¹. In addition, the oligomers were characterized by Fourier-transform infrared spectroscopy (FTIR), matrix-assisted laser desorption/ionization (MALDI-TOF-MS), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) techniques.     

Asymmetric aza-[2,3]-Wittig sigmatropic rearrangements: chiral auxiliary control and formal asymmetric synthesis of (2S, 3R, 4R)-4-hydroxy-3-methylproline and (-)-kainic acid

A survey of 16 different chiral auxiliaries and a variety of strategies found that an (-)-8-phenylmenthol ester of a glycine derived migrating group can control the absolute stereochemistry of aza-[2,3]-Wittig sigmatropic rearrangements with diastereoselectivities of ca. 3 : 1 with respect to the auxiliary. In two specific examples, ca. 50% yields of enantiomerically pure products were obtained after chromatographic purification. These were synthetically manipulated with no erosion of stereochemistry into intermediates that completed formal asymmetric syntheses of (+)-HyMePro and (-)-kainic acid.     

Expeditious synthesis of 2,3-dihydroquinazolin-4(1H)-ones in aqueous medium using thiamine hydrochloride (VB1) as a mild,efficient, and reusable organocatalyst

A simple and straightforward synthesis of 2,3-dihydroquinazolin-4(1H)-ones is developed by reacting anthranilamide with various aldehydes or ketones under mild reaction conditions, using thiamine hydrochloride as a cost-effective, readily available, and green catalyst in water. Simple purification process, high yields within short reaction time, wide substrate scope, operational simplicity, and reusability of the catalyst up to three cycles enrich the applicability of the protocol.     

Asymmetric synthesis of nonproteinogenic amino acids with l-amino acid transaminase: synthesis of (2S)-2-amino-4-oxo-4-phenylbutyric and (3E,2S)-2-amino-4-phenylbutenoic acids

2,4-Dioxo-4-phenylbutyric acid and 2-oxo-4-phenylbut-3-enoic acid are converted to the corresponding (S)-2-amino acids by recombinant Escherichia coli whole cells over-expressing aromatic transaminase from Enterobacter sp. BK2K-1 (AroATEs) in high yields (68–78%) and high enantiomeric purity (>99%) using l-aspartic acid as an amino donor.     

Bis(oxazoline) Lewis acid catalyzed aldol reactions of pyridine N-oxide aldehydes--synthesis of optically active 2-(1-hydroxyalkyl)pyridine derivatives: development, scope, and total synthesis of an indolizine alkaloid

A new, short, and simplified procedure for the synthesis of optically active pyridine derivatives from pro-chiral pyridine-N-oxides is presented. The catalytic and asymmetric Mukaiyama aldol reaction between ketene silyl acetals and 1-oxypyridine-2-carbaldehyde derivatives catalyzed by chiral copper(II)-bis(oxazoline) complexes gave optically active 2-(hydroxyalkyl)- and 2-(anti-1,2-dihydroxyalkyl)pyridine derivatives in good yields and diastereoselectivities, and in excellent enantioselectivities-up to 99 % enantiomeric excess. As a synthetic application of the developed method, a full account for the asymmetric total synthesis of a nonnatural indolizine alkaloid is provided.     

Malonate-type bis(oxazoline) ligands with sp hybridized bridge carbon: synthesis and application in Friedel-Crafts alkylation and allylic alkylation

A series of simple and new C₂-symmetric diphenylmethylidene malonate-type bis(oxazoline) ligands were synthesized and applied to the Friedel-Crafts reaction and allylic alkylation. The Cu(II) complex of ligand 4b bearing the benzyl group afforded good to excellent enantioselectivity for the F-C adducts (up to >99% ee) between indole and alkylidene malonate, and the palladium complex of ligand 4c bearing the phenyl group afforded excellent enantioselectivity (up to 94% ee) for the allylic alkylation product.     

Novel 3-D framework nickel(II) complex with azide, nicotinic acid, and nicotinate(1-) as coligands: hydrothermal synthesis, structure, and magnetic properties

The hydrothermal reaction of Ni(NO3)2, NaN3, and nicotinic acid (Hnic) yielded a 3-D supramolecular framework complex, [Ni(1.5)(N3)(nic)2(Hnic)]n (1) with unusual magnetic properties. In 1, Hnic and nic-1 coexist and show different coordination modes (mu2-Hnic-N,O, mu2-nic-N,O, and mu3-nic-N,O,O bridging NiII ions), and azide groups adopt mu-1,1 (EO) bridging mode linking NiII ions with an unusual Ni-N-Ni angle.     

Copper iodide nanoparticles on poly(4-vinyl pyridine) as new and green catalyst for multicomponent click synthesis of 1,4-disubstituted-l,2,3-triazoles in water

Poly(4-vinyl pyridine) supported nanoparticle of copper(Ⅰ) iodide is reported as a green and recyclable catalyst for the regioselective synthesis of 1,4-disubstituted-1H-1,2,3-triazoles from benzyl halides,sodium azide and terminal alkynes in water. This catalyst can be recovered by simple filtration and recycled up to 8 consecutive runs without any loss of its efficiency.     

Design and synthesis of 4-(1-(4-chlorobenzyl)-2,3-dioxoindolin-5-yl)-1 -(4-substituted/unsubstituted benzylidene) semicarbazide:Novel agents with analgesic,anti-inflammatory and ulcerogenic properties

A new series of isatin semicarbazide derivatives(7a-7j) were synthesized and characterized by spectroscopic means and elemental analysis.Analgesic and anti-inflammatory screening was performed using tail-flick technique and the carrageenan-induced foot paw edema test respectively.The ulcerogenicity was also determined for all the compounds.Some of the compounds showed moderate enhancement of the activity.Among the synthesized derivatives,compound 7d showed higher analgesic, antiinflammatory and one-third of ulcer index of the reference drug.     

New side chain ferroelectric liquid crystalline polymers based on (2S, 3S)-2-chloro-3-methylpentanoic acid: synthesis and phase behaviour

The synthesis of four new chiral mesogenic monomers (M₁–M₄) and side chain ferroelectric liquid crystalline polymers containing (2S, 3S)-2-chloro-3-methylpentanoate is described. The chemical structures and phase behaviour of the monomers and polymers obtained in this study were characterised by Fourier transform infrared, proton nuclear magnetic resonance, polarising optical microscopy, differential scanning calorimetry, thermogravimetric analysis and X-ray diffraction. The selective reflection of light was investigated with ultraviolet/visible (UV/Vis). Their structure–mesomorphism relationships were discussed. M₁ and P₁ all showed a chiral smectic C (SmC*) phase. M₂ and M₃ revealed a SmC* phase and cholesteric phase, while their corresponding polymers P₂ and P₃ revealed a SmC* phase and smectic A (SmA) phase. M₄ only exhibited a cholesteric phase, whereas the corresponding polymers P₄ showed a SmA phase. Moreover, the selective reflection of light shifted to the long-wavelength region at the SmC* phase range and to the short-wavelength region at the cholesteric range with increasing temperature, respectively. The results seemed to demonstrate that the tendency towards melting temperature (T_m), glass transition temperature (T_g), isotropic temperature (T_i) and mesophase range for the monomers and polymers increased by increasing the mesogenic core rigidity or the number of phenyl ring. The polymerisation effect could lead to higher liquid crystalline to isotropic phase transition temperature, wider mesophase range and more ordered smectic phase formed. In addition, all the obtained polymers had a very good thermal stability and the corresponding T_d increased by increasing the number of phenyl ring.