Concise total synthesis of the marine natural product ageladine A

A total synthesis of ageladine A has been achieved by exploiting a Pictet-Spengler-type condensation between 2-aminohistamine and 4,5-dibromo-2-formylpyrrole as the key step.     

Total synthesis of ageladine A, an angiogenesis inhibitor from the marine sponge Agelas nakamurai

[reaction: see text] A 12-step total synthesis of the tricyclic heteroaromatic marine metabolite ageladine A has been achieved using a 6pi-azaelectrocyclization and a Suzuki-Miyaura coupling of N-Boc-pyrrole-2-boronic acid with a chloropyridine as key steps.     

A new total synthesis of the zinc matrixmetalloproteinase inhibitor ageladine A featuring a biogenetically patterned 6pi-2-azatriene electrocyclization

[reaction: see text] A convergent second generation total synthesis of the heterocyclic marine sponge metabolite ageladine A has been achieved by using a biomimetically inspired 6pi-2-azatriene electrocyclization as the key step for formation of the imidazolopyridine moiety.     

A convergent synthesis of the imidazopyridine scaffold of fluorescent alkaloid ageladine A

A convergent synthesis of the imidazopyridine scaffold of fluorescent alkaloid ageladine A (1) has been achieved, employing 3-amino-2-chloropyridine as the staring material. A carboxylic acid was introduced using n-butyllithium and dry ice as the key reaction.     

A convergent total synthesis of the marine sponge alkaloid ageladine A via a strategic 6π-2-azatriene electrocyclization

A second generation total synthesis of the marine sponge metabolite ageladine A utilizing a biogenetically inspired 6π-2-azaelectrocyclization of triene 34 as the key step is performed to construct the imidazopyridine core of the metabolite.     

A novel synthesis of the 2-amino-1H-imidazol-4-carbaldehyde derivatives and its application to the efficient synthesis of 2-aminoimidazole alkaloids, oroidin, hymenidin, dispacamide, monobromodispacamide, and ageladine A

A novel synthesis of 2-amino-1H-imidazol-4-carbaldehyde derivatives was achieved by the reaction of tert-butoxycarbonylguanidine with 3-bromo-1,1-dimethoxypropan-2-one as a key step. The usefulness of the derivatives as building blocks was proved by accomplishing the efficient synthesis of the representative 2-aminoimidazole alkaloids, oroidin, hymenidin, dispacamide, monobromodispacamide, and ageladine A.     

Synthesis and matrix metalloproteinase-12 inhibitory activity of ageladine A analogs

Synthesis of the 37 ageladine A analogs was accomplished by employing the total synthetic route of natural ageladine A previously explored by us. From the matrix metalloproteinase-12 (MMP-12) inhibitory activity assay carried out using the novel analogs, it appeared evident that the halogen atom at the 2-position of pyrrole ring was essential for the inhibitory activity and that the introduction of a bromine atom into the 4-position of pyrrole ring is very effective for producing potent activity. In addition, exchange of the pyrrole ring to an imidazole ring was extremely effective in increasing activity, and the analog 29 thus obtained was found to show approximately 4 times more potent activity than natural ageladine A.     

Ageladine A: an antiangiogenic matrixmetalloproteinase inhibitor from the marine sponge Agelas nakamurai

A novel MMP inhibitor, ageladine A (1) with antiangiogenic activity was isolated from a marine sponge Agelas nakamurai. Structure 1 was determined by a combination of spectroscopic and chemical methods to be an unprecedented structure of 4-(4,5-dibromo-1H-pyrrol-2-yl)]-1H-imidazo[4,5-c]pyridin-2-amine.     

One‐Pot Evolution of Ageladine A through a Bio‐Inspired Cascade towards Selective Modulators of Neuronal Differentiation

A bio‐inspired cascade reaction has been developed for the construction of the marine natural product ageladine A and a de novo array of its N1‐substituted derivatives. This cascade features a 2‐aminoimidazole formation that is modeled after an arginine post‐translational modification and an aza‐electrocyclization. It can be effectively carried out in a one‐pot procedure from simple anilines or guanidines, leading to structural analogues of ageladine A that had been otherwise synthetically inaccessible. We found that some compounds out of this structurally novel library show a significant activity in modulating the neural differentiation. Namely, these compounds selectively activate or inhibit the differentiation of neural stem cells to neurons, while being negligible in the differentiation to astrocytes. This study represents a successful case in which the native biofunction of a natural product could be altered by structural modifications.     

Wallichanol类天然产物ABC环系合成研究

Wallichanol是一类具有独特桥环结构的二萜天然产物.以2-甲基-1,3-环己二酮作为起始原料,通过高立体选择性的Diels-Alder反应和金催化的炔烃碳环化反应构建Wallichanol的ABC三环核心骨架,共七步路线,总收率为42%.该合成工作为Wallichanol类天然产物全合成奠定了研究基础.     

A metalation strategy for the construction of functionalized naphthalenes: the first synthesis of guieranone A

The first synthesis of the natural product guieranone A is described, demonstrating a one-pot procedure for the synthesis of protected-1,3,6,8-tetraoxygenated naphthalenes and a subsequent directed metalation synthesis of 2-keto naphthalenes.     

Synthesis of the western half of the lolicines and lolitrems

[reaction: see text] The synthesis of the highly substituted indole portion of the complex tremorgenic natural products lolicine A and B is presented. The Diels-Alder reaction of a quinone monoimine enables the synthesis of an appropriately substituted indole. The key step in the synthesis is a tandem isopropenyl cuprate addition/aldol cyclocondensation which provides the necessary functionality for elaboration to the 2,2,5,5-tetramethyltetrahydrofuran.     

The Total Synthesis of the Anti-Coccidial Agents Ws-5995

A total synthesis of the three anti-coccidial agents WS-5995 A, B, and C by a Diels-Alder route is described. An intramolecular lactonization involving the displacement of a chlorine atom on a naphthoquinone was the key step in the synthesis of A.     

Model studies for the synthesis of the antibiotic lactonamycin and the discovery of new reactions and mechanisms for the construction of substituted heterocycles

A new and highly efficient route for the construction of a model for the synthesis of lactonamycin 1 is reported. The chemistry has been utilised for the synthesis of heterocyclic rings, and new reactions for the synthesis of dienes and alkynes are reported.     

Synthesis of the 6-6-6 tricyclic skeleton of the anti-influenza A diterpene wickerol A

A five-step synthesis of the 6-6-6 tricyclic skeleton of the diterpene wickerol A is described. The synthesis features a diastereoselective d-proline-mediated Robinson annulation and N-heterocyclic carbene-catalyzed Stetter reaction as key transformations to give the tricyclic carbon skeleton of this promising anti-influenza A natural product.     

Biomimetic synthesis of the shimalactones

A biomimetic synthesis of shimalactone A and B is described. Its key features are an unprecedented acid-catalyzed cyclization of a dienyl beta-ketolactone and a Stille coupling/8pi-6pi electrocyclization cascade to create the oxabicyclo[2.2.1]heptane and bicyclo[4.2.0]octadiene, respectively. The synthesis is convergent and void of protecting groups.     

Stereoselective synthesis of the polyketide chain of nagahamide A

A carbohydrate based approach for the enantioselective synthesis of the polyketide acid unit present in nagahamide A has been reported. Reductive ring opening of a chiral cyclopropane ketone group to enantioselectively install the methyl and propyl groups, is a salient feature of this synthesis.     

Studies directed toward the synthesis of terreulactone A: rapid construction of the A, B, C rings

[structure: see text]. An efficient, rapid synthesis of the A, B, C rings of terreulactone A is described. Key steps in the synthesis include a diastereoselective benzylic acid rearrangement to create the desired quaternary center at C2 and a mild bromolactonization to assemble the lactonic ring A.     

Total synthesis of (+)-frondosin A. Application of the Ru-catalyzed [5+2] cycloaddition

The first total synthesis of (+)-frondosin A was accomplished in 19 longest linear and 21 total steps from commercially available materials. The key features of the synthesis include a Ru-catalyzed [5+2] cycloaddition, a Claisen rearrangement, and a ring expansion to construct the core of the frondosin A in a diastereoselective and regioselective fashion. This is the first application of a Ru-catalyzed [5+2] cycloaddition in the total synthesis of a natural product. Through this synthesis, the absolute configuration of (+)-frondosin A was established.     

Total Synthesis and Biological Evaluation of the Glycosylated Macrocyclic Antibiotic Mangrolide A

The macrocyclic antibiotic mangrolide A has been described to exhibit potent activity against a number of clinically important Gram‐negative pathogens. Reported is the first enantioselective total synthesis of mangrolide A and derivatives. Salient features of this synthesis include a highly convergent macrocycle preparation, stereoselective synthesis of the disaccharide moiety, and two β‐selective glycosylations. The synthesis of mangrolide A and its analogues enabled the re‐examination of its activity against bacterial pathogens, and only minimal activity was observed.