Synthesis of novel enantiopure fluorinated building blocks from acyclic chiral allylsilanes

[reaction: see text] Homochiral beta-fluorinated gamma,delta-unsaturated carboxylic acids with an allylic fluorinated stereogenic center are available from the corresponding enantiopure allylsilanes. The key step for introduction of the fluorine substituent is an electrophilic fluorodesilylation reaction carried out in the presence of Selectfluor. Reduction of the resulting beta-fluorinated pentenoic acid into the corresponding fluorinated alcohol was also performed leading to the formation of an enantiopure second-generation fluorinated building block.     

Encoded dendrimers with defined chiral composition via'click' reaction of enantiopure building blocks

Dendrimers with end-groups of defined chiral composition have been prepared from alkyne functional enantio-pure building blocks obtained by selective enzymatic (ADH) ketone reductions using click chemistry. Optical rotation and enantioselective enzymatic modification is in agreement with the chiral composition of the dendrimers and permits unique molecular-level encoding of stereoisomeric dendritic libraries.     

Studies on the diastereoselective allylation of aldehydes with enantiopure 2-sulfinylallyl building blocks

A comparative study on the allylation of aldehydes with enantiopure (S_S)-2-(p-tolylsulfonyl)-prop-2-en-1-ol (S_S)-1a and the corresponding chloride (S_S)-1b under two different reaction systems is reported. In general, better yields were obtained from chloride (S_S)-1b, whereas higher diastereoinduction was observed from alcohol (S_S)-1a. The sense of diastereoinduction is the same in both systems and the stereochemistry of the major diastereomer has been determined. Moreover, the configurational stability of the sulfoxide group on the resulting sulfinyl homoallylic alcohols 3 has been proven in each reaction system, which demonstrates the efficiency of the sulfoxide group as chiral auxiliary in these allylation processes. Finally, as an example of the synthetic potential of the resulting adducts, a total synthesis of natural enantioenriched (S)-nicotine from sulfinylalcohol 3h is reported.     

Boronic acid building blocks: tools for self assembly

Dynamic covalent functionality has been acknowledged as a powerful tool for the construction of organised architectures, the reversible nature thermodynamically facilitates self-control and self-correction. The use of boronic acids complexation with diols and their congeners has already shown great promise in realising and developing reversible boron-containing multicomponent systems with dynamic covalent functionality. The structure-directing potential has lead to the development of a variety of self-organisation involving not only macrocycles, cages and capsules, but also porous covalent organic frameworks and polymers. Structure controls as well as remarkable synthesis are highlighted in this feature article.     

Aminobenzoates as building blocks for natural product assembly lines

The ortho-, meta-, and para- regioisomers of aminobenzoate are building blocks for a wide range of microbial natural products. Both the ortho-isomer (anthranilate) and PABA derive from the central shikimate pathway metabolite chorismate while the meta-isomer is not available by that route and starts from UDP-3-aminoglucose. PABA is largely funnelled into folate biosynthesis while anthranilate is the scaffold for biosynthetic elaboration into many natural heterocycles, most notably with its role in indole formation for tryptophan biosynthesis. Anthranilate is also converted to benzodiazepinones, fumiquinazolines, quinoxalines, phenoxazines, benzoxazolinates, quinolones, and phenazines, often with redox enzyme participation. The 5-hydroxy form of 3-aminobenzaote is the starter unit for ansa-bridged rifamycins, ansamitocins, and geldanamycins, whereas regioisomers 2-hydroxy, 4-hydroxy and 2,4-dihydroxy-3-aminobenzoate are key components of antimycin, grixazone, and platencin and platensimycin biosynthesis, respectively. The enzymatic mechanisms for generation of the aminobenzoate regioisomers and their subsequent utilization for diverse heterocycle and macrocycle construction are examined.     

Stereoisomeric sugar-derived indolizines as versatile building blocks: synthesis of enantiopure di- and tetrahydroxyindolizidines.

The synthesis of the sugar-derived (1S,2R,8aR)-1,2-di-O-isopropylidene-1,2,3,5,6,8a-hexahydro-5-oxoindolizine (8) and by analogy of the corresponding stereoisomers ent-8 and ent-7, an epimer at C2 of ent-8, has been accomplished in a straightforward manner. The carbon-carbon double bond and the carbonyl functionalities on the six-membered ring make these nitrogen-containing heterocycles useful building blocks for the efficient preparation of a variety of enantiopure polyhydroxylated indolizidines of interest for their glycosidase inhibitory activity. We report here the synthesis of 2,8a-diepilentiginosine 12 from 8 and the preparation of stereoisomeric 1,2,7,8-tetrahydroxyindolizidines 9-11 performed by OsO4-catalyzed double bond syn dihydroxylation of 7 and 8, followed by deoxygenation of the amide group.     

Cysteamine-modified ZIF-8 colloidal building blocks: Direct assembly of nanoparticulate MOF films on gold surfaces via thiol chemistry

Chemical modification of metal organic framework (MOF) nanocrystal colloids was used to endow them with chemical affinity for gold substrates. Modified nanocrystals were then used as building blocks for rapid and selective self-assembly of porous films. Cysteamine (Cys, 2-aminoetanethiol) was chosen as both chemical modulator and functionalizing agent of Zeolite Imidazolate Framework-8 (ZIF-8) MOF nanocrystals. Important parameters such as the impact of the modulator on the range of nanocrystals stability, size, polydispersity, morphology, and crystalline structure were assessed via both, small and wide angle x-ray scattering (SAXS and WAXS). Cysteamine modified ZIF-8 nanocrystals were assembled into films over conductive Au substrates and film growth was followed in-situ with Quartz Crystal Microbalance (QCM). Thiol moieties exposed out of the ZIF-8 surface after cysteamine modification, results in the formation of thiol bonds with Au conductive substrates as shown via Cyclic Voltammetry experiments. The strategy here presented allows for the synthesis of pre-designed building blocks for MOF films on metal surfaces.     

New building blocks for the assembly of sequence selective molecular zippers

Synthetic H-bonded molecular zippers contain no sequence information that can be used to engineer the selective binding interactions characteristic of biopolymers; reversing the sense of the amide bonds in the two binding partners generates a new orthogonal recognition motif and the mutually complementary binding partners form complexes an order of magnitude more stable than the corresponding mismatch complexes.     

Directed assembly of metal-organic cubes from deliberately predesigned molecular building blocks

A novel anionic metal-organic cube (MOC-1), [Ni(8)(HImDC)(12)](8-), has been synthesized by metal-ligand directed assembly of eight tri-connected Ni nodes and twelve doubly deprotonated bis(bidentate) imidazoledicarboxylic acid ligands (HImDC).     

Synthons as building blocks in the synthesis of liquid crystalline multiblock copolymers

Synthetic approaches which allow to insert rather long fragments with exactly definite sequence of several single structural units into polymer chains are considered and summarized. The procedure consists in preliminary formation of such sequences in a form of bifunctional “complex monomer” (synthons) which may undergo a polycondensation with other single or complex monomer to form macromolecule with definite alternation of several single monomers. These synthetic approaches were used for the synthesis of LC multi-block copolymers with definite structure of rigid block.     

Synthesis of iduronic acid building blocks for the modular assembly of glycosaminoglycans

The modular synthesis of glycosaminoglycans requires straightforward methods for the production of large quantities of protected uronic acid building blocks. In particular, the preparation of fully differentiated iduronic acids has proven particularly challenging. An efficient route to methyl 3-O-benzyl-1,2-O-isopropylidene-alpha-l-idopyranosiduronate 6 from diacetone glucose in nine steps and 36% overall yield is described. Idopyranosiduronate 6 is useful as a glycosyl acceptor and as an intermediate that may be further elaborated into iduronic acid trichloroacetimidate glycosyl donors for the assembly of glycosaminoglycan structures as illustrated here.     

Biomolecule-directed assembly of nanoscale building blocks studied via lattice Monte Carlo simulation

We perform lattice Monte Carlo simulations to study the self-assembly of functionalized inorganic nanoscale building blocks using recognitive biomolecule linkers. We develop a minimal coarse-grained lattice model for the nanoscale building block (NBB) and the recognitive linkers. Using this model, we explore the influence of the size ratio of linker length to NBB diameter on the assembly process and the structural properties of the resulting aggregates, including the spatial distribution of NBBs and aggregate topology. We find the constant-kernel Smoluchowski theory of diffusion-limited cluster-cluster aggregation describes the aggregation kinetics for certain size ratios.     

Concise, efficient and practical assembly of bromo-5,6-dimethoxyindole building blocks

A concise, efficient and simple route to a series of bromoindole building blocks is described. The synthetic routes are highlighted by purification-free preparation of o-nitrocinnamate intermediates and clean, modified Cadogan indole syntheses. The scope of this indole synthesis has been explored and expanded through the use of a range of solvents and easily removable phosphine reagents.     

Catalytic asymmetric synthesis of enantiopure isoprenoid building blocks: application in the synthesis of apple leafminer pheromones

The first catalytic asymmetric procedure capable of preparing all 4 diastereoisomers (ee > 99%, de > 98%) of a versatile saturated isoprenoid building block was developed and the value of this new method was demonstrated in its application to the concise total synthesis of two pheromones.