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Azadipyrromethenes were first described over 70 years ago as blue pigments, but now are rapidly emerging as a compound class with highly desirable near infrared photophysical properties. Since the turn of the century several routes to azadipyrromethenes have been developed and numerous post-synthesis derivatizations have allowed for their exploitation in both biological and material sciences. The relative ease of access to specifically designed derivatives is now allowing their use in multiple technological formats from real-time fluorescence imaging, to solar energy materials, to optoelectronic devices and many more. In this review we have highlighted the synthetic component of this story as it is the ability to generate the designer azadipyrromethene that opens the door to exciting applications.

Highly stereoselective aza-Peterson olefinations from bench-stable α,α-bis(trimethylsilyl)toluene reagents and N-substituted imines have been achieved using TMSO(-)/Bu4N(+) as Lewis base activator in THF. Remarkably, and for the first time, N-t-butanesulfinyl imines were utilized for the synthesis of Z-stilbenes with excellent selectivities, while N-aryl imines generated E-stilbenes under identical reaction conditions. The protocol proved general for numerous examples with low molecular weight byproducts formed. The origin of the Z-selectivity is proposed to be a result of diastereoselective addition to N-t-butanesulfinyl imines followed by syn-elimination of an in situ formed hypervalent silicate.

Addition of organotrimethylsilane reagents to chiral N-tert-butanesulfinyl imines can be achieved in good yields and with excellent diastereoselectivities by employing TMSO(-)/Bu4N(+) as a Lewis base activator in THF. A variety of aliphatic, aromatic, heteroaromatic and organometallic chiral imines were utilised as electrophiles for the synthesis of enantioenriched N-tert-butanesulfinyl amides. Remarkably, the same sets of reaction conditions could be used with a highly diverse range of bench-stable organotrimethylsilane reagents, which highlights the generality and robustness of this methodology.

Highly regioselective benzylic metalations in hydrocarbon solvent have been achieved at rt and 0 °C using a mixed-metal Li/K-TMP amide comprised of KOtBu, BuLi, and 2,2,6,6,-tetramethylpiperidine (TMP(H)). Mixing of KOtBu, BuLi, and TMP(H) in heptane gave a solution of the base mixture which when used in deuterium labeling experiments confirmed the requirement of the three reagent components for both reactivity and selectivity. The reaction protocol is operationally straightforward and found to be applicable to a broad range of substrates. Upon generation of the metalated products, they are reacted in heptane at ambient temperature in a variety of synthetically useful ways. Illustrated examples include generation of the benzyltrimethylsilanes and α,α-bis(trimethylsilyl)toluenes reagents, which are bench-stable surrogates of benzyl anions and α-silyl carbanions utilized for nucleophilic addition and Peterson olefination reactions. Direct C-C couplings mediated by 1,2-dibromoethane provided entries into bibenzyls and [2.2]metacyclophanes. Comparison of reaction outcomes with the same reactions carried out in THF at -78 °C showed no negative effects for conducting the reactions under these milder more user-friendly conditions.

A new general two-step approach for the synthesis of bench-stable α,α-bis(trimethylsilyl)toluenes and tris(trimethylsilane) is developed.

The addition of a broad variety of substituted aromatic and heterocyclic silanes to chiral N-tert-butanesulfinylimines has been achieved providing 1,1-diaryl and diheterocyclic substituted sulfinamides with excellent diastereoselectivity in all cases. Employing Me3SiO–/Bu4N+ as the Lewis base activator for silicon allowed a general procedure for all silane reagents, including the less reactive aromatic derivatives. Evidence that the diastereoselective additions occur via an open transition state is presented.

Tms-OK/Bu4NCl is used as a general activator of organotrimethylsilanes for addition reaction.

The use of K2S2O8 in combination with Pd(OAc)2 as catalyst in a solvent mixture of AcOH and acetonitrile gives efficient access to trisubstituted alkenes.

A general one-pot procedure for the synthesis of benzyltrimethylsilanes (III) is developed.

The final enantioselective step is achieved using a (-)-sparteine mediated aryl lithiation, followed by treatment with various electrophiles.

Presently, producers are striving to create products which contain a value added factor, such as dietary fibre or in more recent times, phytochemicals. The production and addition of such nutrients can be quite costly for the producer. In the fruit and vegetable industry, the preparation and processing procedures can lead to one third of the product being discarded. This can be costly for the manufacturer and also may have a negative impact on the environment. Research has shown that these by-products can have a high nutritional value. It has also been suggested, that they could be used as a food ingredient due to their functional abilities such as gelling and water binding. The focus of this review is on the nutritional and functional properties of the by-products of food processing and their potential applications as nutritional new ingredients in foods. Industrial relevance Processors are constantly trying to utilize as much of their product as possible, and this paper puts forward an alternative use for their ‘waste’ which would be of a significant benefit to their business.This new food ingredient contains a nutritional benefit, such as dietary fibre, vitamins and minerals and bio-actives such as flavonoids and lycopene.Due to the nature of the by-products, functionally they hold such properties as increased water holding and binding, gelling and thickening.This review suggests a solution for creating a cheaper value-added ingredient which in turn decreases the present ways of disposing these by-products (which can be harmful to the environment), while also saving the producer's money.Ingredient companies are continually looking for cheaper but value-added ingredients; this paper reflects the opportunity for fruit and vegetable byproducts.

An efficient access to 3-hydroxymethylindoles (III) by using homogeneous continuous-flow microreactor technology is reported.

Reaction of aromatic aldehydes and certain α,β-insaturated carbonyl compounds with 1,2-bis(chlorodimethylsilyl)ethane and zinc leads to products of symmetrical dicarbonyl coupling.

A stereoselective Lewis acid promoted reaction of 5-hydroxynaphthoquinone ( 6 ) and diene ( 10 ) gave the adduct ( 11) as the sole cycloaddition product. This was transformed into the title compound ( 1 ) by a three step procedure in 47% overall yield from ( 6 ).

Synthesis of a range of new bicyclic and tricyclic fused oxazolo[4,5-d]-1,2,3-triazole systems is described. Treatment of these with acid caused transformations to substituted 1,3,4,5-oxatriazine and new 1,2,3-triazaspiroalkane systems which were isolated in high yields. Kinetic studies of the ring transformations indicated the presence of a delocalised carbocation intermediate and the mechanism of the ring expansion and contraction is discussed.

The syntheses of the angucyclinone antibiotics; (±)-rubiginone B13 and B24, (±)-ochromycinone 7, and (±)-emycin A 12 are reported. The key step for the construction of the benzo[a]anthracene nucleus in each of the syntheses was a highly stereoselective, tetra-O-acetyl diborate-promoted Diels–Alder cycloaddition of 5-hydroxy-1,4-naphthoquinone 8 and the diene, E-(1R*,5R*)-l-acetoxy-3-(2′-methoxyvinyl)-5-methylcyclohex-2-ene 21. Base-induced aromatisation of the cycloadduct 30 gave the benzo[a]anthraquinone, (1R*,3R*)-1-acetoxy-8-hydroxy-1,2,3,4-tetrahydrobenzo[a]anthracene-7,12-dione 28 which served as an intermediate for the syntheses of the above natural products. The syntheses of (±)-13-norrubiginone B134 and B235, and (±)-1-epi-rubiginone B111 using modifications of the synthetic strategy are also described.

The first asymmetric synthesis of the angucyclinone antibiotics, emycin A and ochromycinone, is achieved via a short, efficient sequence from 5-hydroxy-1,4-naphthoquinone with the key step being an effective kinetic resolution of a racemic diene in a Diels–Alder reaction promoted by a chiral Lewis acid derived from (S)-3,3′-diphenyl-1,1′-biaphthalene-2,2′-diol.

The angucycline antibiotics have attracted a great deal of attention in the past decade due to their interesting biological properties.1 Although several procedures for the synthesis of individual angucyclines have been reported,2 an efficient general asymmetric method has yet to be developed. We have recently reported a synthesis of the racemic forms of rubiginone B1 (1) and B2 (2), emycin A (3), and ochromycinone (4),2i,j,m which were synthesized from the common intermediate (()-5a formed from the highly stereoselective tetra-O-acetyl diborate promoted Diels-Alder reaction of juglone (5hydroxy-1,4-naphthoquinone) and the diene (()-6a. In an extension of this work, the reaction of juglone with diene (()-6b promoted by a Lewis acid derived from (S)(+)-3,3′-diphenyl-1,1′-binaphthalene-2,2′-diol and BH3‚ THF gave cycloadduct (+)-5b (ee >98%). Modification of (+)-5b resulted in the syntheses of 3 and 4 in enantiomerically pure form.3 In an attempt to extend the versatility of this DielsAlder strategy our attention turned toward angucyclines possessing aromatic A ring and hydroaromatic B ring functionality. We felt that intermediates similar to (+)5b could serve as precursors to PD 1167404 (7), which has been shown to exhibit in vitro activity against L1210 lymphocytic leukaemia and HCT-8 human colon adenocarcinoma cell lines, and the aglycon of TAN 10855 (8), which shows angiogenesis inhibition. The easily accessible Diels-Alder cycloadduct (()-92m would serve as an appropriate model to ascertain the viability of our approach. Our synthetic strategy is outlined in Scheme 1. We felt protected trans diol functionality at C-5 and C-6 could be introduced by epoxidation of the C-4a-C-5 double bond. Examination of the crystal structure of a closely related cycloadduct3 indicated that oxidation would occur from the face of the alkene anti to the C-6 methoxyl group. A neutral oxidant would be required as cycloadduct 9 is unstable under

Two new securinega-type alkaloids, isobubbialine and epibubbialine, were isolated from the leaves of Phyllanthus amarus, as well as the three known alkaloids, phyllanthine, securinine and norsecurinine. The structures of the unknown compounds were determined by means of UV, IR, mass and NMR spectroscopy.

The reaction of octaethylporphyrin iron(III) chloride with potassium crown ether (18-crown-6) nitrite in N-methylpyrrolidone−1% acetic acid under argon generates the iron(III) nitrite salt (PFeNO2). The latter is a unique and selective oxygen atom transfer reagent. The reaction of a broad range of substrates (S) proceeds quantitatively to yield the oxidized substrate and the iron(II) porphyrin−nitrosyl adduct: PFeNO2 + S → PFeNO + SO. Diatomic molecules to which oxygen is directly transferred from PFeNO2 are NO, CO, and O2. The conversion NO to NO2 is shown via 15NO2- labeling experiments to proceed exclusively by the O atom transfer process. The ozone, generated from dioxygen, was trapped with nitrite ion and the two olefins 2-methyl-2 butene and 2,3-dimethyl-2 butene. These substances are inert to PFeNO2 under argon. However, in an oxygen-saturated reaction mixture, nitrite produced nitrate. The olefins, following reduction of the reaction mixture with Zn/HOAc, yielded 1 mol of acetone and acetaldehyde...

An asymmetric synthesis of homochiral α-amino acids has been developed which is based on the conjugate addition of organocuprates to the dehydroalanine equivalent (3S)-N,N′-bis(p-methoxybenzyl)-3-isopropyl-6-methylenepiperazine-2,5-dione 6.

Chlorins bearing synthetic handles at specific sites about the perimeter of the macrocycle constitute valuable building blocks. We previously developed methodology for preparing meso-substituted chlorin building blocks and now present methodology for preparing several complementary beta-substituted chlorin building blocks. The chlorins bear one or two beta substituents, one meso substituent, a geminal dimethyl group to lock in the chlorin hydrogenation level, and no flanking meso and beta substituents. The synthesis involves convergent joining of an Eastern half and a Western half. New routes have been developed to two beta-substituted bromo-dipyrromethane monocarbinols (Eastern halves). A new beta-substituted Western half was prepared following the method for preparing an unsubstituted Western half (3,3-dimethyl-2,3-dihydrodipyrrin). Chlorin formation is achieved by a two-flask process of acid-catalyzed condensation followed by metal-mediated oxidative cyclization. beta-Substituted chlorins have been prepared in 18-24% yield bearing a 4-iodophenyl group at the 8-position, a 4-iodophenyl group or a 4-[2-(trimethylsilyl)ethynyl]phenyl group at the 12-position, and a 4-iodophenyl group and a 4-[2-(trimethylsilyl)ethynyl]phenyl group at diametrically opposed beta-positions (2, 12). The latter building block makes possible the stepwise construction of linear multi-chlorin architectures. The chlorins exhibit typical absorption and fluorescence spectra. A systematic shift in the absorption maximum (637-655 nm for the free base chlorins, 606-628 nm for the zinc chlorins) and intensity of the chlorin Q(y)() band (epsilon up to 79 000 M(-)(1) cm(-)(1)) is observed depending on the location of the substituents. The characteristic spectral features and location of substituents in defined positions make these chlorins well suited for a variety of applications in biomimetic and materials chemistry.

Addition of a range of organocuprates to (S)-N,N′-bis(p-methoxybenzyl)-3-methylene-6-isopropylpiperazine-2,5-dione 8 affords cis-3-isopropyl-6-alkyldiketopiperazines in excellent yield and >95% de. Subsequent deprotection and hydrolysis of these cis-3-isopropyl-6-alkyldiketopiperazines affords homochiral (S)-α-amino acids in excellent yield.

A methodology for the microwave parallel synthesis of libraries is described. The procedure involves the use of an array of expandable reaction vessels, which can accommodate pressure buildup within the vessel due to heating without loss of volatile solvents or reagents. A demonstration 24-membered library of substituted 4(5)-sulfanyl-1H-imidazoles was generated by both conventional and microwave procedures, achieving a reduction from 12 h to 16 min in library generation time for the microwave approach.

A novel structural analogue of kynurenine, 2-amino-4-[3'-hydroxyphenyl]-4-hydroxybutanoic acid 6, was synthesised as an inhibitor of kynureninase. The compound had a significant inhibitory effect on kynureninase from both rat and human, giving a K(i) of 100 nM. It was thus found that removal of the aryl amino group coupled with a reduction of the carbonyl group at position 7 of the alanine side chain greatly enhanced potency of the inhibitor.

The synthesis of functionalized styrene derivatives can be readily achieved utilizing a Suzuki cross-coupling protocol between aryl halides and 2,4,6-trivinylcyclotriboroxane-pyridine complex. The scope and limitations of the procedure were demonstrated by investigation of an array of ortho-substituted aryl halides.