Pathways for the Production of Pharmaceutical Grade Synthetic Phospholipids

Abstract

Two routes are described for the synthesis of pharmaceutical grade phospholipids at the multi-kilogram scale.     

Synthetic strategies and functional reactivity of versatile thiophene synthons

Abstract

Thiophenes are a highly important group of heterocycles and have been of great interest to researchers due to their various reactivities. Many synthetic strategies are used to generate functionalized thiophene derivatives. Several reactions are described, depending on the reactivity of the substituents attached to the thiophene nucleus toward different nucleophiles to yield the versatile thiophene products. Many diverse applications have been utilized for thiophenes from medicinal chemistry to material science.     

Rapid and convenient semi-automated microwave-assisted solid-phase synthesis of arylopeptoids

A facile and expedient route to the synthesis of arylopeptoid oligomers (N-alkylated aminomethyl benz-amides) using semi-automated microwave-assisted solid-phase synthesis is presented. The synthesis was optimized for the incorporation of side chains derived from sterically hindered or unreactive amines and both ortho- and para-substituted arylo-backbones. By utilizing this optimized protocol a complex nonameric arylopeptoid was synthesized in less than 11 h, featuring a novel alternating ortho-, meta-, and para-substituted backbone pattern and a variety of chemically diverse and challenging side chains.     

片呐醇的绿色合成

综述了近年来片呐醇绿色合成研究的新进展,主要包括微波、超声波、固相合成、电合成、光化学合成等新技术、新试剂在该反应中的应用。     

Chemoenzymatic Synthesis of Advanced Intermediates for Formal Total Syntheses of Tetrodotoxin

Advanced intermediates for the syntheses of tetrodotoxin reported by the groups of Fukuyama, Alonso, and Sato were prepared. Key steps include the toluene dioxygenase mediated dihydroxylation of either iodobenzene or benzyl acetate. The resulting diene diols were transformed into Fukuyama's intermediate in six steps, into Alonso's intermediate in nine steps, and into Sato's intermediate in ten steps.     

片呐醇的绿色合成

综述了近年来片呐醇绿色合成研究的新进展,主要包括微波、超声波、固相合成、电合成、光化学合成等新技术、新试剂在该反应中的应用。     

Preparation of Optically Enriched Secondary Alkyllithium and Alkylcopper Reagents—Synthesis of (−)‐Lardolure and Siphonarienal

Optically enriched secondary alkyl iodides were converted into secondary alkyllithium and secondary alkylcopper compounds with very high retention of configuration. Quenching with various electrophiles, including chiral epoxides, provided a range of chiral molecules with high enantiomeric purity (>90 % ee). This method has been applied in an iterative fashion in the total synthesis of (?)‐lardolure in 13 steps and 5.4 % overall yield (>99 % ee, dr>99:1) and siphonarienal in 15 steps and 5.6 % overall yield (>99 % ee, dr>99:1) starting from commercially available ethyl (R)‐3‐hydroxybutyrate (>99 % ee).     

Advances in the Chemical Synthesis of Artemisinin

Artemisinin, existing in the Chinese medicinal plant Artemisia annua L., is a kind of sesquiterpenoid lactone endoperoxide. It has received extensive attention from all over the world owing to its unusual trioxane structure and potent antimalarial properties. Here we demonstrate the complete chemical synthetic pathway of artemisinin, investigated the past three decades, including the total and partial syntheses.     

Total Synthesis of (−)‐Ophiodilactone A and (−)‐Ophiodilactone B

The first asymmetric total synthesis of (?)‐ophiodilactone A and (?)‐ophiodilactone B, isolated from the ophiuroid (Ophiocoma scolopendrina), is reported. The key features of the synthesis include the highly stereocontrolled construction of the structurally congested γ‐lactone/δ‐lactone skeleton through an asymmetric epoxidation, diastereoselective iodolactonization, and intramolecular epoxide‐opening with a carboxylic acid, and biomimetic radical cyclization of ophiodilactone A to ophiodilactone B.     

绿色合成：一个逐步形成的学科前沿

绿色合成是有机合成化学面向新世纪的学科前沿。本文探讨绿色合成的目标及实现这一目标的一些可能途径。     

Solid-Phase-Supported Chemoenzymatic Synthesis of a Light-Activatable tRNA Derivative

Herein, we present a multi-cycle chemoenzymatic synthesis of modified RNA with simplified solid-phase handling to overcome size limitations of RNA synthesis. It combines the advantages of classical chemical solid-phase synthesis and enzymatic synthesis using magnetic streptavidin beads and biotinylated RNA. Successful introduction of light-controllable RNA nucleotides into the tRNA^Met sequence was confirmed by gel electrophoresis and mass spectrometry. The methods tolerate modifications in the RNA phosphodiester backbone and allow introductions of photocaged and photoswitchable nucleotides as well as photocleavable strand breaks and fluorophores.     

烯胺酮(酯)类化合物合成研究进展

本文综述了目前国内外烯胺酮(酯)类化合物的主要合成方法。从采用缩合、加成、取代及杂环分解等不同的反应类型,采用路易斯酸、无机酸等不同的催化剂体系,以及采用微波或超声波促进,利用离子液体作为反应介质等几个方面展开讨论。     

Redox Divergent Synthesis of Fawcettimine‐Type Lycopodium Alkaloids

A new approach for synthesis of fawcettimine‐type Lycopodium alkaloids is described. A divergent strategy was achieved by applying stereoselective Diels–Alder reaction followed by redox‐controlled elaboration. Eventually, (?)‐8‐deoxyserratinine, (+)‐fawcettimine, (?)‐lycopoclavamine‐A, (?)‐serratine, (?)‐lycopoclavamine‐B and (?)‐serratanidine were successfully accessed.     

Stereoselective allyl amine synthesis through enantioselective addition of diethylzinc and [1,3]-chirality transfer: synthesis of lentiginosine and polyoxamic acid derivative

A new synthetic method for the preparation of allyl amines has been developed. The key steps of this method are enantioselective addition of diethylzinc and [1,3]-chirality transfer through the [3.3] sigmatropic rearrangement of allyl cyanates. Stereocontrolled syntheses of lentiginosine (1) and polyoxamic acid derivative 2 from a common intermediate 7 derived from D-tartaric acid (8), have been accomplished.     

Divergent strategy in natural product total synthesis

Divergent strategy in natural product synthesis allows the comprehensive synthesis of family natural products. Efficient formulation of this idea requires the biosynthetic/biosynthesis-inspired insight toward the well-orchestrated design of a pluripotent late-stage intermediate, in concomitant with the applicability of the intermediates for versatile transformations. This digest focuses on the actual applications of those strategies in natural product synthesis with an emphasis on the recipes for the choice of the common intermediates.     

天然产物骆驼宁碱A及其衍生物的合成研究进展

骆驼宁碱A是从骆驼蒿中分离出来的喹唑啉酮类生物碱, 骆驼蒿在中国民间用来治疗风湿病、炎症、脓肿及其他疾病. 由于骆驼宁碱A的药理活性, 有关其合成方法受到了关注. 综述了该化合物的合成方法, 根据闭环方式的不同把合成方法分为六大类, 大部分方法都围绕中间体喹啉吡咯烷酮的合成, 一般步骤较长, 产率过低, 虽然有的路线步骤短, 产率高, 但原料不易得到. 因此, 经济的产业化方法还有待进一步研究.     

Biomimetic total synthesis of (+)-gelsemine

Challenging: (+)-gelsemine was synthesized from (R,R)-aziridine 1 in 25 steps with approximately 1 % overall yield. A multistep, one-pot enol-oxonium cyclization cascade was used to construct, simultaneously, the E ring, F ring, C3 stereocenter, and C7 quaternary stereocenter. This synthesis using the enol-oxonium cyclization reaction as a key step to make the cage structure has demonstrated the proposed biosynthetic pathway of the gelsemine family.     

An operationally simple,fast and green synthesis of novel γ-hydroxyphosphonate and phosphine oxide derivatives

A green and versatile method for the preparation of γ-hydroxyphosphonate and phosphine oxide derivatives in 5?min, is accomplished through the reduction of γ-phosphonylketones with sodium borohydride supported on alumina, at room temperature, under solvent free conditions.