关于可控组装的一些思考（一）——从催化到催组装

分子组装的范畴和复杂性远歹乇于合成反应,但是它们有着相同目标,即高选择性和高效率地创造新物质和制备新功能材料．因此,我们尝试将合成中广泛应用的催化概念拓展至组装研究,提出用于调控和加速组装过程的催组装（cassemblysis）的新思路．为此,我们将迄今泛用的自组装、助组装等术语重新进行规范和分类,即所有的分子组装可分为自组装和助组装．绝大多数组装属于助组装,这可进一步分为催组装、共组装和外场助组装3大类．催组装中的催组剂（cassemblyst）类似于合成中的催化剂,可在不改变总吉布斯自由能变化的条件下加速组装过程,催组装因此有望成为在分子以上层次高选择性且高效率地创造新物质的最佳途径．一些催组装体系在组装之后还会进一步进行化学耦联反应,由此显著提高产物的稳定性,组装与耦联总过程可称为催组联（catassemblysis）．我们分别在小分子和生物大分子两个层次上,分析说明了迄今已被不自觉使用的催组装和催组联的一些典型事例,提出了光电催组装的设想,比较了与催组装关联的纳米粒子组装体系,探讨了与催组装相关的简要模型和机理．本：炙强调,在开展可控组装研究中,不仅要设计与合成各种新组装基元,而且要注重构建催组剂和催组联剂,发展催组装的实验和理论方法学,揭示催组剂作用于组装基元的机理,将有望推动可控组装在创造新物质和制备新功能材料方面发挥更大作用．     

Monodisperse nanocrystals: general synthesis, assembly, and their applications

This article summarizes the recent advances in the synthesis, assembly and applications of monodisperse nanocrystals, which may be suggestive for the designed synthesis and assemblies of target nanocrystals according to practical requirements.     

4 + 2]-annulations of chiral organosilanes: Application to the total synthesis of leucascandrolide A

Complete details of an asymmetric synthesis of leucascandrolide A (1) are described. The synthesis highlights the use of two diastereoselective [4 + 2]-annulations for the assembly of the functionalized bispyranyl macrolide 3. An efficient assembly and union of the oxazole-containing side chain 4 with macrolide 3 was carried out using a Mitsunobu reaction. A convergent route to the oxazole side chain was developed using a Sonogashira cross-coupling between 2-trifloyloxazole 16 and alkyne 17, which allowed for the installation of the C9'-C10' (Z)-olefin.     

Engineering Multifunctional DNA Hybrid Nanospheres through Coordination‐Driven Self‐Assembly

Developing simple and general approaches for the synthesis of nanometer‐sized DNA materials with specific morphologies and functionalities is important for various applications. Herein, a novel approach for the synthesis of a new set of DNA‐based nanoarchitectures through coordination‐driven self‐assembly of Fe^II ions and DNA molecules is reported. By fine‐tuning the assembly, Fe–DNA nanospheres of precise sizes and controlled compositions can be produced. The hybrid nanoparticles can be tailored for delivery of functional DNA to cells in vitro and in vivo with enhanced biological function. This highlights the potential of metal ion coordination as a tool for directing the assembly of DNA architectures, which conceptualizes a new pathway to expand the repertoire of DNA‐based nanomaterials. This methodology will advance both the fields of DNA nanobiotechnology and metal–ligand coordination chemistry.     

A synthesis of camptothecin

A total synthesis of camptothecin has been carried out. Central to our synthesis is the intramolecular condensation of a suitably designed ketol, which in turn was obtained from a tricyclic ABC ring synthon. A tandem reductive amination and Michael addition sequence on an unsaturated quinoline ester was employed for the assembly of the ABC skeleton.     

Biomimetic and aggregation-driven crystallization route for room-temperature material synthesis: growth of beta-Ga(2)O(3) nanoparticles on peptide assemblies as nanoreactors

The room-temperature synthesis of beta-Ga2O3 nanocrystal was examined by coupling two biomimetic crystallization techniques, enzymatic peptide nanoassembly templating and aggregation-driven crystallization. The catalytic template of peptide assembly nucleated and mineralized primary beta-Ga2O3 crystals and then fused them to grow single-crystalline and monodisperse nanoparticles in the cavity of the peptide assembly at room temperature. In this work, the peptide assembly was exploited as a nanoreactor with an enzymatic functionality catalyzing the hydrolysis of gallium precursors. In addition, the characteristic ring structure of peptide assembly is expected to provide an efficient dehydration pathway and crystallization control over the surface tension, which are advantageous for beta-Ga2O3 crystal growth. This multifunctional peptide assembly could be applied for syntheses of a variety of nanomaterials that are kinetically difficult to grow at room temperature.     

Cluster‐Based Self‐Assembly Route toward MoO3 Single‐Walled Nanotubes

MoO₃ has a unique rigid double‐layer structure, which makes it a real challenge to prepare nanotubular structures. The controlled synthesis of MoO₃ single‐walled nanotubes (SWNTs) is achieved through a cluster‐based self‐assembly route on the dodecanethiol/water interface. Various factors are studied at length, including precursor type, reaction time, temperature, pH value, and their influence on the morphology of products. The concept of “self‐assembly—from simple clusters to nanostructures” is proposed here based on preliminary results from the synthesis of MoO₃ SWNTs, which provides a new aspect for traditional synthetic chemistry of nanomaterials and polyoxometalates.     

Modular Synthesis of Nona-Decasaccharide Motif from Psidium guajava Polysaccharides: Orthogonal One-Pot Glycosylation Strategy

The synthesis of long, branched, and complex carbohydrate sequences remains a challenging task in chemical synthesis. Reported here is an efficient and modular one-pot synthesis of a nona-decasaccharide and shorter sequences from Psidium guajava polysaccharides, which have the potent α-glucosidase inhibitory activity. The synthetic strategy features: 1) several one-pot glycosylation reactions on the basis of N-phenyltrifluoroacetimidate (PTFAI) and Yu glycosylation to streamline the chemical synthesis of oligosaccharides, 2) the successful and efficient assembly sequences (first O3′, second O5′, final O2′) toward the challenging 2,3,5-branched Araf motif, 3) the stereoselective 1,2-cis-glucosylation by reagent control, and 4) the convergent [6+6+7] one-pot coupling reaction for the final assembly of the target nona-decasaccharide. This orthogonal one-pot glycosylation strategy can streamline the chemical synthesis of long, branched, and complicated carbohydrate chains.     

A New Approach to the Synthesis of Cortical Steroids

A new bondset for cortical steroid synthesis is developed from the dual concepts of convergent assembly and multiple construction. A short synthesis on this bondset is presented in which the final bond construction by electrocyclization took an unwanted course. Stereocontrol is discussed separately.     

Divergent heparin oligosaccharide synthesis with preinstalled sulfate esters

Traditional chemical synthesis of heparin oligosaccharides first involves assembly of the full length oligosaccharide backbone followed by sulfation. Herein, we report an alternative strategy in which the O-sulfate was introduced onto glycosyl building blocks as a trichloroethyl ester prior to assembly of the full length oligosaccharide. This allowed divergent preparation of both sulfated and non-sulfated building blocks from common advanced intermediates. The O-sulfate esters were found to be stable during glycosylation as well as typical synthetic manipulations encountered during heparin oligosaccharide synthesis. Furthermore, the presence of sulfate esters in both glycosyl donors and acceptors did not adversely affect the glycosylation yields, which enabled us to assemble multiple heparin oligosaccharides with preinstalled 6-O-sulfates.     

Protein synthesis by solid-phase chemical ligation using a safety catch linker

The native chemical ligation reaction has been used extensively for the synthesis of the large polypeptides that correspond to folded proteins and domains. The efficiency of the synthesis of the target protein is highly dependent on the number of peptide segments in the synthesis. Assembly of proteins from multiple components requires repeated purification and lyophilization steps that give rise to considerable handling losses. In principle, performing the ligation reactions on a solid support would eliminate these inefficient steps and increase the yield of the protein assembly. A new strategy is described for the assembly of large polypeptides on a solid support that utilizes a highly stable safety catch acid-labile linker. This amide generating linker is compatible with a wide range of N-terminal protecting groups and ligation chemistries. The utility of the methodology is demonstrated by a three-segment synthesis of vMIP I, a chemokine that contains all 20 natural amino acids and has two disulfide bonds. The crude polypeptide product was recovered quantitatively from the solid support and purified in 20%-recovered yield. This strategy should facilitate the synthesis of large polypeptides and should find useful applications in the assembly of protein libraries.     

Total synthesis of bryostatins: the development of methodology for the atom-economic and stereoselective synthesis of the ring C subunit

Bryostatins, a family of structurally complicated macrolides, exhibit an exceptional range of biological activities. The limited availability and structural complexity of these molecules makes development of an efficient total synthesis particularly important. This article describes our initial efforts towards the total synthesis of bryostatins, in which chemoselective and atom-economical methods for the stereoselective assembly of the ring C subunit were developed. A Pd-catalyzed tandem alkyne-alkyne coupling/6-endo-dig cyclization sequence was explored and successfully pursued in the synthesis of a dihydropyran ring system. Elaboration of this methodology ultimately led to a concise synthesis of the ring C subunit of bryostatins.     

Copper(II)‐Mediated Self‐Assembly of Hairpin Peptides and Templated Synthesis of CuS Nanowires

The self‐assembly of peptides and proteins under well‐controlled conditions underlies important nanostructuring processes that could be harnessed in practical applications. Herein, the synthesis of a new hairpin peptide containing four histidine residues is reported and the self‐assembly process mediated by metal ions is explored. The work involves the combined use of circular dichroism, NMR spectroscopy, UV/Vis spectroscopy, AFM, and TEM to follow the structural and morphological details of the metal‐coordination‐mediated folding and self‐assembly of the peptide. The results indicate that by forming a tetragonal coordination geometry with four histidine residues, copper(II) ions selectively trigger the peptide to fold and then self‐assemble into nanofibrils. Furthermore, the copper(II)‐bound nanofibrils template the synthesis of CuS nanowires, which display a near‐infrared laser‐induced thermal effect.     

Nanoarchitectonics beyond Self‐Assembly: Challenges to Create Bio‐Like Hierarchic Organization

Incorporation of non‐equilibrium actions in the sequence of self‐assembly processes would be an effective means to establish bio‐like high functionality hierarchical assemblies. As a novel methodology beyond self‐assembly, nanoarchitectonics, which has as its aim the fabrication of functional materials systems from nanoscopic units through the methodological fusion of nanotechnology with other scientific disciplines including organic synthesis, supramolecular chemistry, microfabrication, and bio‐process, has been applied to this strategy. The application of non‐equilibrium factors to conventional self‐assembly processes is discussed on the basis of examples of directed assembly, Langmuir–Blodgett assembly, and layer‐by‐layer assembly. In particular, examples of the fabrication of hierarchical functional structures using bio‐active components such as proteins or by the combination of bio‐components and two‐dimensional nanomaterials, are described. Methodologies described in this review article highlight possible approaches using the nanoarchitectonics concept beyond self‐assembly for creation of bio‐like higher functionalities and hierarchical structural organization.     

Modular Synthesis of Nona‐Decasaccharide Motif from Psidium guajava Polysaccharides: Orthogonal One‐Pot Glycosylation Strategy

The synthesis of long, branched, and complex carbohydrate sequences remains a challenging task in chemical synthesis. Reported here is an efficient and modular one‐pot synthesis of a nona‐decasaccharide and shorter sequences from Psidium guajava polysaccharides, which have the potent α‐glucosidase inhibitory activity. The synthetic strategy features: 1) several one‐pot glycosylation reactions on the basis of N‐phenyltrifluoroacetimidate (PTFAI) and Yu glycosylation to streamline the chemical synthesis of oligosaccharides, 2) the successful and efficient assembly sequences (first O3′, second O5′, final O2′) toward the challenging 2,3,5‐branched Araf motif, 3) the stereoselective 1,2‐cis‐glucosylation by reagent control, and 4) the convergent [6+6+7] one‐pot coupling reaction for the final assembly of the target nona‐decasaccharide. This orthogonal one‐pot glycosylation strategy can streamline the chemical synthesis of long, branched, and complicated carbohydrate chains.     

FHBC,a Hexa‐peri‐hexabenzocoronene–Fluorene Hybrid: A Platform for Highly Soluble,Easily Functionalizable HBCs with an Expanded Graphitic Core

Materials based upon hexa‐peri‐hexabenzocoronenes (HBCs) show significant promise in a variety of photovoltaic applications. There remains the need, however, for a soluble, versatile, HBC‐based platform, which can be tailored by incorporation of electroactive groups or groups that can prompt self‐assembly. The synthesis of a HBC–fluorene hybrid is presented that contains an expanded graphitic core that is highly soluble, resists aggregation, and can be readily functionalized at its vertices. This new HBC platform can be tailored to incorporate six electroactive groups at its vertices, as exemplified by a facile synthesis of a representative hexaaryl derivative of FHBC. Synthesis of new FHBC derivatives, containing electroactive functional groups that can allow controlled self‐assembly, may serve as potential long‐range charge‐transfer materials for photovoltaic applications.     

Synthesis of the Trypanosoma cruzi LPPG heptasaccharyl myo-inositol

Synthesis of the heptasaccharyl myo-inositol found in Trypanosoma cruzi lipopeptidophosphoglycan was accomplished using a convergent assembly of three building blocks. The target compound is the first complete 2-aminoethyl phosphonic acid substituted glycan related to the glycosylphosphatidylinositol anchor family to be synthesized. The order of assembly enables synthesis of phosphoinositol oligosaccharides related to other glycosylinositolphospholipids in Tr. cruzi, the protozoan parasite causing Chagas' disease, which is endemic in South America.     

Modular Synthesis of a Tridecasaccharide Motif of Bacteroides vulgatus Lipopolysaccharides against Inflammatory Bowel Diseases through an Orthogonal One-Pot Glycosylation Strategy

Lipopolysaccharides from Bacteroides vulgatus represent interesting targets for the treatment of inflammatory bowel diseases. However, efficient access to long, branched and complex lipopolysaccharides remains challenging. Herein, we report the modular synthesis of a tridecasaccharide from Bacteroides vulgates through an orthogonal one-pot glycosylation strategy based on glycosyl ortho-(1-phenylvinyl)benzoates, which avoids the issues of thioglycoside-based one-pot synthesis. Our approach also features: 1) 5,7-O-di-tert-butylsilylene-directed glycosylation for stereoselective construction of the α-Kdo linkage; 2) hydrogen-bond-mediated aglycone delivery for the stereoselective formation of β-mannosidic bonds; 3) remote anchimeric assistance for stereoselective assembly of the α-fucosyl linkage; 4) several orthogonal one-pot synthetic steps and strategic use of orthogonal protecting groups to streamline oligosaccharide assembly; 5) convergent [1+6+6] one-pot synthesis of the target.     

Studies toward the total synthesis of gambieric acids: convergent synthesis of the GHIJ-ring fragment having a side chain

A stereocontrolled synthesis of the GHIJ-ring fragment having a side chain of gambieric acids, which are potent antifungal polycyclic ether natural products, has been achieved. The synthesis features convergent assembly of the tetracyclic polyether skeleton by using aldol coupling and stereoselective construction of the J-ring side chain by a cerium chloride-promoted Julia-Kocienski reaction.     

FHBC,a Hexa‐peri‐hexabenzocoronene–Fluorene Hybrid: A Platform for Highly Soluble,Easily Functionalizable HBCs with an Expanded Graphitic Core

Materials based upon hexa‐peri‐hexabenzocoronenes (HBCs) show significant promise in a variety of photovoltaic applications. There remains the need, however, for a soluble, versatile, HBC‐based platform, which can be tailored by incorporation of electroactive groups or groups that can prompt self‐assembly. The synthesis of a HBC–fluorene hybrid is presented that contains an expanded graphitic core that is highly soluble, resists aggregation, and can be readily functionalized at its vertices. This new HBC platform can be tailored to incorporate six electroactive groups at its vertices, as exemplified by a facile synthesis of a representative hexaaryl derivative of FHBC. Synthesis of new FHBC derivatives, containing electroactive functional groups that can allow controlled self‐assembly, may serve as potential long‐range charge‐transfer materials for photovoltaic applications.