The shortest synthetic route to puromycin analogues using a modified Robins approach

We are reporting on the utility of commercial vinyl isocyanate for a practical synthetic route from adenosine to N(6)-bis-demethylpuromycin in seven steps and 65% overall yield. A clean one-pot conversion of 3'-bromo-2'-carbamoyl derivative 8 to 3'-amino-3'-deoxyadenosine derivative 10 is the main feature of this synthetic pathway. This synthesis is the shortest synthetic route toward 3'-(aminoacylamido)deoxyadenosines to date.     

The succinct synthesis of AT13387, a clinically relevant Hsp90 inhibitor

AT13387 is an orally bioavailable clinical candidate developed to inhibit heat shock protein 90 (Hsp90). This article describes a modified synthetic route for the multi-gram production of AT13387 in 46% overall yield. The modified synthetic route is short, avoids stringent reaction conditions and difficult purifications, which led to an increase in overall yield.     

Development of a scalable synthetic route towards a 2,2,6-trisubstituted chiral morpholine via stereoselective hydroalkoxylation

A scalable synthetic route towards a chiral 2,2,6-trisubstituted chiral morpholine, which is a known opioid antagonist, was developed. The synthetic route involves incorporating an aryl group via Suzuki-Miyaura coupling and stereoselective hydroalkoxylation catalyzed by trifluoromethanesulfonic acid. Late stage incorporation of both the aryl and N-alkyl groups make this route suitable for further SAR studies on this molecule.     

Rapid access to conformational analogues of (+)-peloruside A

An efficient synthetic strategy for rapid access to analogues of peloruside A has been demonstrated. The synthetic route was highlighted by a simple esterification-based fragment coupling and a late stage ring-closing metathesis reaction. This convergent route has provided access to rationally designed analogues inspired by the solution conformational preferences of peloruside A.     

Towards the development of synthetic routes using theoretical calculations: an application of in silico screening to 2,6-dimethylchroman-4-one

This study describes an attempt to develop a synthetic route using theoretical calculations, i.e., in silico synthesis route development. The KOSP program created four potential synthetic routes for generating 2,6-dimethylchroman-4-one. In silico screening of these four synthetic routes was then performed. In silico screening involves theoretical analysis of synthetic routes prior to actual experimental work. A synthetic route using the Mitsunobu reaction had already been reported by Hoddgets et al. Theoretical investigations were also conducted on two S(N)Ar reactions as well as a Michael reaction before they were examined experimentally. In silico screening using DFT calculations indicated that only the Michael reaction was likely to produce the target. Experimental work confirmed that the target was obtained in a yield of 76.4% using the Michael reaction. The other two routes, except for the Mitsunobu reaction, failed to generate the target. Our results demonstrate that theoretical calculations can be used to narrow down the number of experiments that need to be conducted when developing novel synthetic routes.     

Total synthesis of an oxepine natural product, (±)-janoxepin

The total synthesis of (±)-janoxepin, a novel antiplasmodial d-leucine derived oxepine-pyrimidinone-ketopiperazine isolated from the fungus Aspergillus janus, is described. The cornerstones of the synthetic route are pyrimidinone preparation, ring-closing metathesis, aldol introduction of the enamide, and dihydro-oxepine elaboration. This synthetic route proved very efficient for the formation of a number of janoxepin analogues, including dihydro-janoxepin and tetrahydro-janoxepin.     

Study on a New Method for Synthesis of Mirabegron

Mirabegron is a muscle relaxing drug for the treatment of overactive bladder. The existing synthetic methods for mirabegron produced intermediate product 4‐(2‐(phenethylamino)ethyl)aniline, which complicated the final product purification process. In this study, we designed a new synthetic route for mirabegron with low cost starting materials and a production of mirabegron at a 99.6% purity and a 61% overall yield. Particularly, this new synthetic route did not produce side product 4‐(2‐(phenethylamino)ethyl)aniline, which significantly simplified the product purification process.     

The facile synthesis of 5-formylporphyrin

A facile synthetic route of 5-formylporphyrin(2) has been developed.Using pyrrole and pivaldehyde as the starting materials,2 was obtained through several facile reactions.The synthetic route is easy to perform and can be scaled up,which gives the compound a better application perspective.     

Two novel syntheses of the histamine H3 antagonist thioperamide

The previously described route for the synthesis of the histamine H₃ antagonist thioperamide 3 has been improved considerably. Furthermore, two straightforward novel synthetic routes towards 3 are described herein. The last synthetic route (Scheme 3) is preferable as it is very suitable for the production of multigram quantities of thioperamide 3.     

A facile and rapid access towards the synthesis of 2,3-dihydroquinazolin-4(1H)-ones

An efficient synthetic route for 2,3-dihydroquinazolin-4(1H)-ones using 2-morpholinoethanesulfonic acid as a potential and new organocatalyst is described. The developed synthetic protocol represents a novel and very simple route for the preparation of 2,3-dihydroquinazolin-4(1H)-one derivatives. In addition, microwave irradiation technique is successfully implemented for carrying out the reactions in shorter reaction times.     

An alternative synthesis of Tamiflu: a synthetic challenge and the identification of a ruthenium-catalyzed dihydroxylation route

Synthetic studies of Tamiflu^® and the identification of a ruthenium-catalyzed dihydroxylation route are disclosed. This newly developed synthetic process circumvents the need for a Mitsunobu inversion step and the use of explosive reagents. This route, therefore, compares favorably to the previously developed synthetic process.     

Practical synthesis of chiral ligands for catalytic enantioselective cyanosilylation of ketones and ketoimines

A practical synthesis of chiral ligands that are useful for catalytic enantioselective cyanosilylation of ketones and ketoimines is described. Compared with the previous synthetic route, the number of total steps is decreased and the total yield is greatly improved. Furthermore, both (+)- and (-)-ligands are readily available by this new synthetic route.     

Concise synthetic strategy toward cyclic α,α-disubstituted α-amino acids bearing a δ-nitrogen atom: chiral 1-substituted 4-aminopiperidine-4-carboxylic acids

A concise synthetic strategy toward cyclic α,α-disubstituted α-amino acids, 1-substituted 4-aminopiperidine-4-carboxylic acids have been developed. The synthetic route is a reductive amination of dimethyl bis(dioxolanemethyl)malonate with various amines, followed by Curtius rearrangement. This synthetic route is capable of synthesizing 4-aminopiperidine-4-carboxylic acids bearing a bulky substituent and optically active ones bearing a pendent chiral substituent, by the change of condensed amines.     

Synthesis of 5-(Sulfamoylmethyl)indoles by Mild Negishi Coupling and Their Application in Almotriptan

A new synthetic route of almotriptan was described. The application of Negishi coupling reaction simplified the process and significantly improved the yield. The synthetic route was also expected to be general for the synthesis of other tryptamines like sumatriptan and avitriptan.     

New synthesis route for the preparation of pomalidomide

A new route for the preparation of pomalidomide is described in the study. The synthetic procedure starts from 4-nitroisobenzofuran-1,3-dione and 3-aminopiperidine-2,6-dione hydrochloride via a three-step reaction resulting in a total yield of 65% with a high-performance liquid chromatographic (HPLC) purity of 99.56% and a low palladium residue level of 2 ppm. This method can be deemed as an efficient, practical, and environmentally friendly synthetic route for the preparation of pomalidomide.     

A microwave improvement in the synthesis of the quinazoline scaffold

A rapid and efficient microwave-assisted protocol is described that greatly improves a recent synthetic method developed for quinazoline synthesis. The synthetic protocol is based on the use of cycles of microwave irradiation. The optimization process is reported and the experimental results are compared with those of the conventional synthetic route.     

Enantioselective synthesis of N1999A2

An enantioselective synthetic route to the enediyne antibiotic N1999A2 (1) is described, proceeding in 21 steps (0.4% yield, 77% average yield per step) from (R)-(+)-glycidol. The route involves the convergent assembly of three components: a (1-iodovinyl) stannane (2), a 1,5-hexadiyne-3,4-diol derivative (3), and a substituted naphthoic acid (4). Important transformations in the synthetic sequence include the palladium-catalyzed coupling of 2 and 3, an intramolecular oxidative cyclization of a terminal bisacetylene, and a transannular anionic (bi)cyclization of a cyclic bromoenetriyne. The careful selection and manipulation of protective groups throughout the sequence proved to be critical to the development of the synthetic route, where all late-stage intermediates were unstable and could not be concentrated. In the final step of the sequence, three protective groups were removed in a single operation, providing synthetic N1999A2 (1) in 76% yield. Conditions were found that, for the first time, led to the precipitation of 1 as a solid.     

A facile synthesis of the oxazolidinone antibacterial agent linezolid

A facile synthetic route of linezolid 1 has been developed.Using commercially available(R)epichlorohydrin as the starting material,1 was obtained through a sequence of cyclization,substitution, a Goldberg coupling,aminolysis and acetylation reactions.The synthetic route is easy to perform and can be scaled up.     

Stream-lined synthesis of 3-hydroxy-β-lactams: Norrish-Yang type II photocyclizations of β-ketoformamides

A photochemical approach to 3-phenyl-3-hydroxy-β-lactams (3-HβLs) is reported. Irradiation of aryl-β-ketoformamides with a UV light band centered at 300?nm provides the corresponding 3-aryl-3-HβLs with good conversion. The scope of the photocyclization is explored with an electronically diverse panel of substrates that provides mechanistic insight supporting a Norrish-Yang type II cyclization. A flexible synthetic route to phenyl-β-ketoformamides, followed by photoirradiation, allows for efficient incorporation of the β-lactam pharmacophore into aromatic organic scaffolds. Taken collectively, the improved and optimized synthetic route to provide both β-ketoformamides and 3-HβLs—in combination with the expanded analysis of substrate scope and limitations—reported herein will serve as a necessary reference for the direct, atom-economical, radical-mediated installation of 3-HβL scaffolds en route to the generation of other biologically active small molecules.     

六方相NaYF4:Yb/Er纳米晶制备方法研究进展

综述了六方相NaYF4:Yb/Er纳米晶的制备方法,着重总结了三氟乙酸盐热分解法、共沉淀法、碳酸盐热分解法、离子热法、水热法及两步法的研究进展,并就其发展前景进行了展望.