A total synthesis of millingtonine A

A total synthesis of millingtonine A, a diglycosylated alkaloid, has been accomplished. Millingtonine A possesses a unique racemic tricyclic core structure not known from any other natural or synthetic source until now. The synthesis features a key bond-forming radical Ueno-Stork cyclization to form the heterocyclic core.     

Bioinspired Total Synthesis of Complex Nucleoside Antibiotics A201A,A201D and A201E

Herein, bioinspired total syntheses of A201A, A201D, and A201E based on a previously reported biosynthetic pathway are presented. The challenging 1,2-cis-furanoside, a core structure of the A201 family, was obtained by remote 2-quinolinecarbonyl-assisted glycosylation. We accomplished the total synthesis of A201A and A201E based on the critical 1,2-cis-furanoside moiety through late-stage glycosylation without any interference from basic dimethyl adenosine. We also confirmed the absolute configuration of A201E by total synthesis. This modular synthesis strategy enables efficient preparation of A201 family antibiotics, allowing the study of their structure–activity relationships and mode of action. This study satisfies the increasing demand for developing novel antibiotics inspired by the A201 family.     

Bioinspired Total Synthesis of Complex Nucleoside Antibiotics A201A,A201D and A201E

Herein, bioinspired total syntheses of A201A, A201D, and A201E based on a previously reported biosynthetic pathway are presented. The challenging 1,2-cis-furanoside, a core structure of the A201 family, was obtained by remote 2-quinolinecarbonyl-assisted glycosylation. We accomplished the total synthesis of A201A and A201E based on the critical 1,2-cis-furanoside moiety through late-stage glycosylation without any interference from basic dimethyl adenosine. We also confirmed the absolute configuration of A201E by total synthesis. This modular synthesis strategy enables efficient preparation of A201 family antibiotics, allowing the study of their structure–activity relationships and mode of action. This study satisfies the increasing demand for developing novel antibiotics inspired by the A201 family.     

A simple stereocontrolled synthesis of salinosporamide A

A simple and effective stereocontrolled synthesis of salinosporamide A has been developed. This process, the first synthesis of salinosporamide A, is capable of providing the compound in substantial quantities for further biological studies. Salinosporamide A was of special interest as a synthetic target because of its potent in vitro cytotoxic activity against many tumor cell lines (IC(50) values of 10 nM or less).     

A short total synthesis of sulfobacin A

A total synthesis of the von Willebrand factor receptor antagonist sulfobacin A is described. Key steps for this short route to sulfobacin A include ruthenium-catalyzed asymmetric hydrogenation and diastereoselective electrophilic amination for the construction of the three stereogenic centers.     

A formal total synthesis of leucascandrolide A

A convergent synthesis of the macrocyclic core of the marine macrolide leucascandrolide A has been accomplished.     

A total synthesis of phomactin A

A total synthesis of phomactin A (1) based on a Cr(II)/Ni(II) macrocyclisation from the aldehyde vinyl iodide 11, leading to 12, followed by elaboration of the epoxyketone 16, which then undergoes spontaneous pyran-hemiacetal formation on deprotection, is described.     

A total synthesis of mycalisine A

In this paper, we report a total synthesis of a naturally occurring pyrrolo[2,3-d]pyrimidine nucleoside, mycalisine A. Our synthetic strategy uses D-xylose as the startingmaterial and Vorbrüggen glycosylation as the key step. Mycalisine A was synthesized in 11 steps with a 15% overall yield.     

A stereoselective formal synthesis of leucascandrolide A

A stereoselective formal synthesis of leucascandrolide A was accomplished through the tandem and organocatalytic oxa-Michael reactions, which were promoted by the gem-disubstituent effect, in conjunction with the dithiane coupling reaction.     

Synthesis of jenamidines A1/A2

[reaction: see text] Addition of the enolate of tert-butyl acetate to cyanamide methyl ester 17 followed by treatment with LHMDS afforded vinylogous urea 19 in 27% yield. Vinylogous urea 19 was also obtained from 37 and tert-butyl cyanoacetate in 50% yield. Acylation of 19 with acid chloride 31d, followed by hydrolysis of the tert-butyl ester and decarboxylation with 9:1 CH2Cl2/TFA and very mild basic hydrolysis of the methoxyacetate ester, afforded jenamidines A1/A2 (3) in 45% yield. This first synthesis confirms our reassignment of the jenamidines A1/A2 structure.     

A concise total synthesis of salinosporamide A

A concise and straightforward 14-step total synthesis of (+/-)-salinosporamide A, based on a diastereoselective acid-catalysed intramolecular cyclisation of to the pyrrolidinone , and a regioselective reduction of the malonate derivative 8b to the aldehyde 9, is described.     

Enantioselective syntheses of tremulenediol A and tremulenolide A

A concise entry to the skeleton of the tremulane sesquiterpenes is described that culminated in the first enantioselective syntheses of tremulenediol A and tremulenolide A. The approach features a series of efficient transition metal-catalyzed reactions commencing with an enantioselective rhodium(II)-catalyzed intramolecular cyclopropanation followed by a regioselective allylic alkylation and a diastereoselective rhodium(I)-catalyzed [5+2] cycloaddition.     

Asymmetric Synthesis of the Ring A Substructure of Genkwadane A

A practical approach to the asymmetric synthesis of the ring A substructure of genkwadane A, a daphnane diterpenoid, was developed. This synthesis features the Mukaiyama aldol reaction to introduce the quaternary stereogenic center at C4 and VO(acac)₂‐catalyzed Jackson‐Ellman‐Bolm sulfoxidation to deliver the corresponding sulfoxide. The Dieckmann‐type condensation was efficiently promoted by KHMDS and the ring A substructure was finally accomplished through Barton iodination condition.     

Separation of gibberellin A4 from A4 and A7 mixture by selective complex

<正>Gibberellin A4 is effectively separated from mixture of gibberellin A4 and its analogue gibberellin A7,in the form of its crystalline complex with N,N,N',N'-tetramethylethylenediamine.After removing the tetramethylethylenediamine from the crystal by dilute HCl,gibberellin A4 is obtained a purity of 98.1%and a yield of 72.7%.     

Pre-resonance Raman studies of some mesogens-TB4A, TB7A and TB10A

Pre-resonance Raman spectra of certain liquid crystalline compounds, TB4A, TB7A and TB10A, are reported. The anomaly observed in the pre-resonance Raman spectra in the three compounds was initially explained by the Albrecht-Hutley Model, but its failure leads us to explain the anomalous intensity enhancement mechanism by invoking an interference effect between a weak dipole-forbidden excited state and a nearby strong electronic level via vibrational modes. The presence of a 2¹A_g dipole-forbidden excited state in TB4A and TB10A is deduced after an elaborate discussion of their centro-symmetric structure. The structural difference of TB7A in comparison with TB4A and TB10A is also discussed by taking their X-ray data into consideration.     

Pre-resonance Raman studies of some mesogens-TB4A,TB7A and TB10A

Pre-resonance Raman spectra of certain liquid crystalline compounds, TB4A, TB7A and TB10A, are reported. The anomaly observed in the pre-resonance Raman spectra in the three compounds was initially explained by the Albrecht-Hutley Model, but its failure leads us to explain the anomalous intensity enhancement mechanism by invoking an interference effect between a weak dipole-forbidden excited state and a nearby strong electronic level via vibrational modes. The presence of a 2¹A_g dipole-forbidden excited state in TB4A and TB10A is deduced after an elaborate discussion of their centro-symmetric structure. The structural difference of TB7A in comparison with TB4A and TB10A is also discussed by taking their X-ray data into consideration.     

A concise total synthesis of naamidine A

[reaction: see text]. A total synthesis of naamidine A is reported. Key benefits of the described pathway include its brevity, its synthetic ease, and its flexibility with respect to the preparation of analogues. Formation of the 2-aminoimidazole core is achieved by condensation of the appropriate alpha-aminoketone with cyanamide.     

A short enantioselective synthesis of a component of cryptophycin A and arenastatin A

Synthesis of 1, a component of cryptophycin A 2 and arenastatin A 3, was achieved by applying palladium-catalyzed reductive ring opening of optically active alkenyl oxirane 13 for the construction of the vicinal stereogenic centers.     

Synthesis of the proposed structure of plakevulin A: revised structure of plakevulin A

A total synthesis of the proposed structure of plakevulin A was accomplished. However, the NMR spectral data of the synthetic plakevulin A were not identical of those of the reported compound. We next converted the synthetic plakevulin A into 1-dihydrountenone A. The ¹H and ¹³C NMR spectral data of 1-dihydrountenone A were identical with those of reported plakevulin A except for the peaks derived from levulinic acid. Thus, we repurified sample of the natural product and confirmed that the natural sample contained 1-dihydrountenone A and levulinic acid in the ratio of one to one. We also found that not plakevulin A but 1-dihydountenone A possessed the inhibitory activity against mammalian DNA polymerases α and β.     

A mechanistic study of Protein A chromatography resin lifetime

A mechanistic study into Protein A chromatographic resin lifetime limitations is presented. Binding and mass transport properties of two widely used agarose-based Protein A resins were studied to distinguish between the roles of resin fouling due to product/impurity build-up and ligand degradation as contributory factors towards the decline in binding capacity with use. Cycling studies were conducted with and without product loading on the columns to separate out the influence of resin fouling. Ligand degradation under the mildly alkaline conditions used for column regeneration was determined to be the primary cause for Protein A resin capacity decline with usage. The use of lower concentrations of caustic and the use of stabilizing excipients to protect the Protein A ligand during cleaning and sanitization were found to be useful techniques in maintaining column performance. The results presented in this paper provide a clearer understanding of the causative factors that limit Protein A chromatographic resin lifetime. It is anticipated that these findings will assist in the development of more robust and economical downstream manufacturing processes for monoclonal antibody and Fc fusion protein purification.