Next‐Generation o‐Nitrobenzyl Photolabile Groups for Light‐Directed Chemistry and Microarray Synthesis

Light as an external trigger is a valuable and easily controllable tool for directing chemical reactions with high spatial and temporal accuracy. Two o‐nitrobenzyl derivatives, benzoyl‐ and thiophenyl‐NPPOC, undergo photo‐deprotection with significantly improved efficiency over that of the commonly used NPPOC group. The two‐ and twelvefold increase in photo‐deprotection efficiency was proven using photolithograph synthesis of microarrays.     

Prometabolites of 5‐Diphospho‐myo‐inositol Pentakisphosphate

Diphospho‐myo‐inositol phosphates (PP‐InsP_y) are an important class of cellular messengers. Thus far, no method for the transport of PP‐InsP_y into living cells is available. Owing to their high negative charge density, PP‐InsP_y will not cross the cell membrane. A strategy to circumvent this issue involves the generation of precursors in which the negative charges are masked with biolabile groups. A PP‐InsP_y prometabolite would require twelve to thirteen biolabile groups, which need to be cleaved by cellular enzymes to release the parent molecules. Such densely modified prometabolites of phosphate esters and anhydrides have never been reported to date. This study discloses the synthesis of such agents and an analysis of their metabolism in tissue homogenates by gel electrophoresis. The acetoxybenzyl‐protected system is capable of releasing 5‐PP‐InsP₅ in mammalian cell/tissue homogenates within a few minutes and can be used to release 5‐PP‐InsP₅ inside cells. These molecules will serve as a platform for the development of fundamental tools required to study PP‐InsP_y physiology.     

天然单萜柠檬烯的微生物转化

天然单萜柠檬烯资源丰富,价格便宜,在日用化工和医药行业已得到重要的应用。近几十年来,以柠檬烯为起始原料的新产品的研究与开发一直受到关注。大量文献报道了微生物能够对柠檬烯进行生物转化,得到系列在化妆品、食品、医药、有机合成等领域有重要应用价值的含氧衍生物。本文系统地综述了柠檬烯的微生物转化菌株和所得到转化产物的结构,分析了微生物对柠檬烯的主要转化途径以及影响微生物转化效率的主要因素。柠檬烯经微生物转化所得到的产物具有区域和立体选择性,并且难以通过人工合成方法得到。对生物转化过程进行系统优化,将有可能实现有用化合物的工业化生产。此外,在转化过程中诱导的高活性酶,尤其是单加氧酶和羟化酶的研究与应用也展现了诱人的前景。     

Synthesis of Cyclic Peptides in SPPS with Npb-OH Photolabile Protecting Group

Significant efforts have been made in recent years to identify more environmentally benign and safe alternatives to side-chain protection and deprotection in solid-phase peptide synthesis (SPPS). Several protecting groups have been endorsed as suitable candidates, but finding a greener protecting group in SPPS has been challenging. Here, based on the 2-(o-nitrophenyl) propan-1-ol (Npp-OH) photolabile protecting group, a structural modification was carried out to synthesize a series of derivatives. Through experimental verification, we found that 3-(o-Nitrophenyl) butan-2-ol (Npb-OH) had a high photo-release rate, high tolerance to the key conditions of Fmoc-SPPS (20% piperidine DMF alkaline solution, and pure TFA acidic solution), and applicability as a carboxyl-protective group in aliphatic and aromatic carboxyl groups. Finally, Npb-OH was successfully applied to the synthesis of head–tail cyclic peptides and side-chain–tail cyclic peptides. Moreover, we found that Npb-OH could effectively resist diketopiperazines (DKP). The α-H of Npb-OH was found to be necessary for its photosensitivity in comparison to 3-(o-Nitrophenyl)but-3-en-2-ol (Npbe-OH) during photolysis-rate verification.     

An improved large scale synthesis of 1,4-anhydro-4-thio-d-ribitol

An improved large scale synthesis of 1,4-anhydro-4-thio-d-ribitol (4) from d-ribose has been accomplished by combining the O-allyl and O-p-methoxybenzyl protecting groups. Compound 4 was obtained in 31% yield in eight steps with three chromatographic separations.     

Studies on Quinones. XIX. Improved Synthesis of 2-Nitro-1,4-benzoquinone and its Reaction with Nucleophiles

Reaction of 2-nitro-1,4-benzoquinone (4), easily obtained by oxidation of 3 with MnO₂/HNO₃, with various nucleophiles affords the corresponding adducts in high yields.     

Expanding the Scope of PNA‐Encoded Synthesis (PES): Mtt‐Protected PNA Fully Orthogonal to Fmoc Chemistry and a Broad Array of Robust Diversity‐Generating Reactions

Nucleic acid‐encoded libraries are emerging as an attractive and highly miniaturized format for the rapid identification of protein ligands. An important criterion in the synthesis of nucleic acid encoded libraries is the scope of reactions that can be used to introduce molecular diversity and devise divergent pathways for diversity‐oriented synthesis (DOS). To date, the protecting group strategies that have been used in peptide nucleic acid (PNA) encoded synthesis (PES) have limited the choice of reactions used in the library synthesis to just a few prototypes. Herein, we describe the preparation of PNA monomers with a protecting group combination (Mtt/Boc) that is orthogonal to Fmoc‐based synthesis and compatible with a large palette of reactions that have been productively used in DOS (palladium cross‐couplings, metathesis, reductive amination, amidation, heterocycle formation, nucleophilic addition, conjugate additions, Pictet–Spengler cyclization). We incorporate γ‐modifications in the PNA backbone that are known to enhance hybridization and solubility. We demonstrate the robustness of this strategy with a library synthesis that is characterized by MALDI MS analysis at every step.     

Mild benzhydrylation and tritylation of saccharidic hydroxyls promoted by acid washed molecular sieves

Commercially available 4 Å acid washed molecular sieves (AW 300 MS) promote the protection of primary and secondary saccharidic alcohols through a dehydration mechanism and in the absence of any strong protic or Lewis acid.     

Kinetic Model of Fixed Bed Reactor with Immobilized Microorganisms for Removing Low-Concentration SO2

On the basis of the analysis of the process of treating low concentrations of sulfur dioxide (SO2) gas in a fixed bed reactor, a kinetic model is proposed for this process after taking into consideration the effects of internal diffusion, cell concentration, and production yield of microorganisms but ignoring the effect of external diffusion. The results obtained from the model simulation show that this model can indicate the influence of the process factors, Cin,η,μmax, Cx,A, h, Km, and Q, on the removal of SO2 and that the prediction of the results by this model is also satisfactory. This kinetic model can also provide some very important indications regarding the preparation of immobilized microorganisms, selection and domestication of proper species of microorganisms, as well as the design of bioreactors.     

Biologically active molecules with a "light switch"

Biologically active compounds which are light-responsive offer experimental possibilities which are otherwise very difficult to achieve. Since light can be manipulated very precisely, for example, with lasers and microscopes rapid jumps in concentration of the active form of molecules are possible with exact control of the area, time, and dosage. The development of such strategies started in the 1970s. This review summarizes new developments of the last five years and deals with "small molecules", proteins, and nucleic acids which can either be irreversibly activated with light (these compounds are referred to as "caged compounds") or reversibly switched between an active and an inactive state.     

烯丙基保护基在多羟基化合物中的应用

烯丙基保护基由于能够在温和的反应条件下,在羟基、氨基等基团中引入和脱除,并且具有很好的区域选择性和化学选择性,因此被广泛应用于有机合成中。本文介绍了烯丙基保护基的发展历史,综述了烯丙保护基对多羟基化合物中不同羟基的选择性保护应用,并阐述了烯丙保护基的引入和脱除的机理及方法。     

A practical method for building linear and cyclic triamines from (2-trimethylsilyl)ethanesulfonamides (SES-amides)

SES-chloride has been obtained in higher yield and purity by improving Weinreb's original procedure, allowing efficient access to the primary SES-amide. Linear triamines can be built conveniently from the SES-amide in high yields, with the potential for orthogonal protection. The modified Richman-Atkins cyclisation of SES-amides allows access to novel biologically interesting triazamacrocycles with combinations of three-, four-, five- and six-carbon bridges within the ring. Purification of the free macrocyclic amines by distillation greatly simplifies the workup, increasing the practicability of multi-gram scale synthesis. Although CsF sometimes provided undesirably low yields in the deprotection step, alternative fluoride sources were found to be unsuitable for the deprotection of SES-triazamacrocycles.