Wenhua Li

Layer-by-Layer Assembled Conductive Metal-Organic Framework Nanofilms for Room-Temperature Chemiresistive Sensing

The utility of electronically conductive metal-organic frameworks (EC-MOFs) in high-performance devices has been limited to date by a lack of high-quality thin film. The controllable thin-film fabrication of an EC-MOF, Cu3 (HHTP)2 , (HHTP=2,3,6,7,10,11-hexahydroxytriphenylene), by a spray layer-by-layer liquid-phase epitaxial method is reported. The Cu3 (HHTP)2 thin film can not only be precisely prepared with thickness increment of about 2u2005nm per growing cycle, but also shows a smooth surface, good crystallinity, and high orientation. The chemiresistor gas sensor based on this high-quality thin film is one of the best room-temperature sensors for NH3 among all reported sensors based on various materials.

Total synthesis of piperazimycin A: a cytotoxic cyclic hexadepsipeptide.

screened using the National Cancer Institute s panel of 60 cancer cell lines, piperazimycin A exhibited in vitro cytotoxicity toward multiple tumor cell lines with a mean GI50 value of 100 nm. Additional analysis revealed that this compound had a nearly three-fold more potent activity against solid tumors than against the leukemia cell lines tested. This selectivity is not enough to support the development piperazimycin A for the treatment of cancer because of the general cytotoxicity. Structure-activity relationship (SAR) studies of this natural product would not only be able to overcome this drawback, but also open a new avenue for exploring the possible mode of action of this compound. However, before comprehensive SAR studies can become a reality, an efficient total synthesis of piperazimycin A is required. Herein, we disclose the first total synthesis of this natural product. Structurally, piperazimycin A is an 18-membered macrocycle which is composed of a hydroxyacetic acid and five rare amino acids. These amino acid residues include an (S)-amethylserine, a novel (S)-2-amino-8-methyl-4,6-nonadienoic acid (S-AMNA), two g-hydroxypiperazic acids ((S,S)gOHPip and (R,R)-gOHPip), and one g-chloropiperazic acid ((R,S)-gClPip). The g-substituted piperazic acid residues have also been found in other antitumor cyclodepsipeptides such as polyoxypeptins, and antibiotic cyclodepsipeptides such as monamycins, himastatin, lydiamycins, and dentigerumycin. The total synthesis of piperazic acid containing natural products has received much attention during the past decades. Although some cyclodepsipeptides with the g-substituted piperazic acid residues have been synthesized successfully, none of them contain a dipeptide unit having two piperazic acid residues (such as (R,S)-gClPip-(S,S)gOHPip in piperazimycin A). This difficult-to-install dipeptide presents a new synthetic challenge. Indeed, we have prepared both the protected (R,S)-gClPip and (S,S)-gOHPip units, but failed in installing them under various conditions, especially using acid chlorides as coupling reagents. Accordingly, we planned to assemble this section of the molecule by forming two piperazine rings only after the connection of their precursors, as indicated in Figure 1. Since the ester part of this molecule is the only less sterically hindered site, we decided to carry out the macrocyclization through an ester bond formation. The synthetic routes to requisite fragments 6 and 8 are illustrated in Scheme 1. Treatment of the known lactone 2 with LiHMDS and subsequent trapping of the resulting anion with MoOPH gave the desired trans-alcohol 3 in 73 % yield (79 % brsm) with a 6:1 diastereoselectivity. The trans-alcohol 3 was reacted with triflic anhydride, and then exposed to benzyl carbazate to afford hydrazide 4 in 81% yield. Protection of 4 with TrocCl led to formation of 5, which upon saponification and subsequent methylation provided a methyl ester, which was chlorinated using Ph3P and CCl4 to deliver 6. In a parallel procedure, the enantiomer of trans-alcohol 3 (ent-3) was reacted with Tf2O and then treated with tert-butyl carbazate to give hydrazide 7 in 88% yield. Removal of the TBDPS ether in 7 by reaction with TBAF and AcOH provided alcohol 8 in quantitative yield. These fragments could then used to assemble the required (R,S)-gClPip/(S,S)gOHPip fragments (see below). Notably, 6 and 8 could be easily converted into protected g-hydroxypiperazic acid and g-chloropiperazic acid, respectively. Although several groups have reported their efforts for assembling these g-substituted piperazic acids, our method apparently represents one of the simplest procedures. Figure 1. Structure of piperazimycin A and its bond disconnection analysis.

Total synthesis of antimicrobial and antitumor cyclic depsipeptides

The total synthesis of natural products has to be viewed as an art and a science that needs to be advanced for its own sake (K. C. Nicolaou) and indeed, the achievements within this field of chemistry during the last decades are astonishing. However, besides its inherent beauty, total synthesis also opens the gates widely to a better understanding of biological processes and the development of pharmaceutical interesting substances. Cyclic depsipeptides form one of the compound classes that have attracted tremendous attention from synthetic chemists. They often feature non-proteinogenic amino acids and various types of structural unique building blocks, which make them challenging targets for synthetic efforts. Their total synthesis offers the chance to implement the use of newly developed synthetic tools in a complex environment. Synthetic dead-ends have shown the limitations of todays chemistry as well as triggering the development of new methodologies to circumvent the observed problems. Cyclic depsipeptides also often possess biological properties, especially antimicrobial and antitumor activity, that make them promising candidates for further pharmaceutical investigations and thus have a value at their own. Furthermore, through construction from scratch, ambiguities regarding the structure of several members of that compound class could be successfully clarified and derivatives for structure-activity-relationship (SAR) studies obtained.

A new azodioxy-linked porphyrin-based semiconductive covalent organic framework with I2 doping-enhanced photoconductivity

A room-temperature solution phase reaction was developed to synthesize a covalent organic framework (COF) for the first time. The synthesized azodioxy-linked porphyrin-based COF (POR-COF) possesses a 2D chess board-like structure in the ab-plane and a 1D channel with an open-window size of around 1.9 nm along the c-axis in the modeled crystal structure. The electrical conductivity of POR-COF increases by more than 3 orders of magnitude through I2 doping. The photoconductivity of the I2-doped COF material was also studied firstly. POR-COF shows interesting doping-enhanced photo-current generation.

A Concise Route to the Proposed Structure of Lydiamycin B, an Antimycobacterial Depsipeptide

The total synthesis of four possible isomers with the proposed structure of antimycobacterial depsipeptide lydiamycin B is achieved. None of them shows identical NMR data with those reported for natural lydiamycin B, indicating that further structural revisions are required.

Construction of Morphan Derivatives by Nitroso–Ene Cyclization: Mechanistic Insight and Total Synthesis of (±)‐Kopsone

A typeu2005II nitroso-ene cyclization was developed for the construction of morphan derivatives with good functional-group tolerance. DFT calculations revealed that the nitroso-ene reaction proceeds in a stepwise manner involving diradical or zwitterionic intermediates. The rate-determining step is C-N bond formation, followed by a rapid hydrogen-transfer step with a chair-conformation transition state. The current approach was also successfully applied in the first total synthesis of (±)-kopsone, a highly strained yet simple morphan-type alkaloid isolated from Kopsia macrophylla.

Chemoenzymatic construction of chiral alkenyl acetylenic alcohol, a key building block to access diastereoisomers of polyacetylenes

BackgroundEnzymatic kinetic resolution is proved as an efficient strategy of accessing chiral secondary alcohols in organic synthesis. Although several synthetic methods have been developed for the preparation of chiral acetylenic alcohol, biotransformation remains as a direct approach in the synthesis of polyacetylene lipids, which represent an intriguing class of marine natural products featuring interesting biological profiles.ResultsNovozym 435, a commercial lipase immobilized on macroporous acrylic resin, is utilized in the kinetic resolution of 1-yn-3-ol-4-(E)-ene (alkenyl acetylenic alcohol), which exists as terminus in recently isolated isofulvinol (1) both from the mollusk Peltodoris atromaculata and the sponge Haliclona fulva. The kinetic resolution enabled by Novozym 435 resulted in acetylenic alcohol and the corresponding acetate both in excellent enantiomeric excess and high isolated yield. The optimized reaction conditions allow us to realize the reaction at room temperature in toluene. The reaction is readily scaled up for synthetic use.ConclusionsThe current investigation builds up a platform for future exploration on stereoisomers of isofulvinol, synthetic intermediates with different chain length, and natural product analogs.