A concise, unified total synthesis of the two prenylated aromatic polyketides amorfrutins A and C, which exhibit various medicinally important biological profiles such as antimicrobial, PPARγ ...modulating and quorum sensing inhibitory activities, has been achieved from commercially available 3,5-dimethoxybenzaldehyde in 38% and 10% overall yields through nine and ten steps, respectively. The key transformation for the synthesis of amorfrutin A was the Claisen rearrangement of a mono-O-(1,1-dimethylallyl)resorcinol derivative to install the C3-prenyl substituent, while that for the synthesis of amorfrutin C was the double Claisen rearrangement of a di-O-(1,1-dimethylallyl)resorcinol derivative to introduce the two prenyl groups at the C3 and C5 positions all at once.
Unified total synthesis of amorfrutins A and C via the Claisen rearrangement.
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•(±)-Orobanchol, a representative canonical strigolactone, was successfully synthesized.•The key acid-mediated cascade cyclization proceeded with almost perfect ...diastereoselectivity.•The overall efficiency is far superior to the best previously reported synthesis.•This cascade cyclization must be based on 4π-electrocyclic reaction and analogous to that in planta.
Strigolactones are a class of apocarotenoids known as rhizosphere semiochemicals and plant hormones that can be classified as either canonical or noncanonical. Although orobanchol has long been known as a representative canonical strigolactone, only two synthetic methods have been reported so far, and both have room for improvement in selectivity and overall efficiency. We report a novel and efficient stereoselective synthesis of (±)-orobanchol using acid-mediated cascade cyclization as a key step. This cascade cyclization is analogous to that occurring in planta and is understood to involve a conrotatory 4π-electrocyclic reaction.
Synthesis of (+)-costic acid, isolated from Dittrichia viscosa (L.) W. Greuter as a natural acaricidal sesquiterpenoid, was achieved in 16 steps from (R)-carvone with an overall yield of 4.8%, ...involving the radical cyclization of selenoester to construct a decalone framework as the key step. Other structurally related natural products, (+)-costal, (+)-costol, and (+)-β-selinene, were also synthesized. The acaricidal activities of these four natural products and some synthetic intermediates were also evaluated against Varroa destructor. Among them, (+)-costal especially exhibited potent acaricidal activity.
Amphiphilic gradient copolymers with poly(ethylene glycol) pendants were synthesized via tandem catalysis of ruthenium-catalyzed living radical polymerization (LRP) and titanium alkoxide-mediated ...transesterification. The gradient sequence can be catalytically controlled by tuning the kinetic balance of the two reactions. The tandem catalysis is one of the most efficient and versatile systems to produce amphiphilic gradient and sequence-controlled copolymers. Typically, methyl methacrylate (MMA) was polymerized as a starting monomer with a ruthenium catalyst and a chloride initiator in the presence of Ti(Oi-Pr)4 and molecular sieves (MS 4A) in poly(ethylene glycol) methyl ether (PEG-OH) as a solvent at 80 °C. Hydrophobic MMA was concurrently transesterified into hydrophilic PEG methacrylate (PEGMA) during LRP to give MMA/PEGMA gradient copolymers. The gradient sequence is directly determined by the instantaneous monomer composition changing from MMA alone to PEGMA-rich mixture in solution. Synchronized catalysis of LRP and transesterification thus affords gradient copolymers whose composition linearly changes from an initiating terminal to a growing counterpart. Additionally, amphiphilic MMA/PEGMA gradient copolymers showed self-assembly, thermoresponsive, and thermal properties specific to the gradient sequence, distinct from amphiphilic random or block counterparts.
Type II polyketide synthases (PKSs) normally synthesize polycyclic aromatic compounds in nature, and the potential to elaborate further diverse skeletons was recently revealed by the discovery of a ...polyene subgroup. Here, we show a type II PKS machinery for the biosynthesis of a five-membered nonaromatic skeleton contained in the nonproteinogenic amino acid cispentacin and the plant toxin coronatine. We successfully produce cispentacin in a heterologous host and reconstruct its biosynthesis using seven recombinant proteins in vitro. Biochemical analyses of each protein reveal the unique enzymatic reactions, indicating that a heterodimer of type II PKS-like enzymes (AmcF-AmcG) catalyzes a single C
elongation as well as a subsequent cyclization on the acyl carrier protein (AmcB) to form a key intermediate with a five-membered ring. The subsequent reactions, which are catalyzed by a collection of type II PKS-like enzymes, are also peculiar. This work further expands the definition of type II PKS and illuminates an unexplored genetic resource for natural products.
The N-acyl amycolose moiety incorporated in amycolamicin, a broad-spectrum antibacterial natural product produced by soil actinomycetes, and its two anomeric methyl glycosides have been synthesized ...enantioselectively each in 12 steps from a known methyl (R)-lactate derivative by exploiting a diastereoselective nucleophilic addition of a p-methoxybenzyloxy-substituted vinyllithium reagent to an α,β-bisalkoxy ketone intermediate to provide the corresponding tertiary alcohol as a single diastereomer. The three sugar derivatives are known as cytotoxic degradation products of amycolamicin.
Perfluorinated gradient copolymers comprising fluorous units and hydrophobic or hydrophilic units were created as fluorous polymer materials with unique physical properties. The gradient copolymers ...were efficiently synthesized via the tandem catalysis of living radical polymerization and titanium alkoxide-mediated transesterification of 1H,1H,2H,2H-perfluorooctyl methacrylate (13FOMA) with alcohols. Owing to the electron-withdrawing perfluorooctyl unit, 13FOMA was efficiently transesterified into another methacrylate (RMA) with alcohols during the copolymerization of 13FOMA and RMA to afford well-controlled 13FOMA/RMA gradient copolymers. The gradient sequence gradually changed from 13FOMA to RMA-rich composition according to monomer composition varying in the polymerization solutions. The tandem catalysis is allowed to use various alcohols including 1-dodecanol, 1-octadecanol, ethanol, and poly(ethylene glycol) methyl ether; the catalysis developed herein is thus one of the most versatile systems to produce fluorous/hydrophobic or fluorous/hydrophilic gradient copolymers. Additionally, physical properties of a fluorous/hydrophobic 13FOMA/dodecyl methacrylate gradient copolymer were investigated. The gradient copolymer exhibited broad glass transition temperature, microphase separation, self-assembly, surface tension, and water/oil repellency distinct from corresponding random or block counterparts.
La-excess compositions of lanthanum silicate apatites (La9.33+0.67xSi6O26+x or La9.33+0.67xSi6–0.5xO26; x > 0) exhibit higher oxide-ion conductivity than basic composition (La9.33Si6O26) due to ...smaller activation energies. On the contrary, the activation energies for oxide-ion conduction tend to increase with more La vacancies, less La content, at the La 4f site. However, the effect of La vacancies on the activation energy of oxide-ion conduction is not fully understood. In the present work, first-principles calculations are performed for La9.33+0.67xSi6O26+x (x = 0.0, 0.5, 1.0) to clarify the relationship between the amount of La vacancy at the La 4f site and the activation energy of oxide-ion migration in the O4 channel. It is found that the potential barrier of oxide-ion migration is extremely low in La10Si6O26 (x = 1.0) whereas that becomes higher with increasing the amount of La 4f vacancies. This is closely related to sizes of La 6h triangles that surround the O4 channel. In the presence of more La 4f vacancies, La 6h triangles tend to be more expanded than those in La10Si6O26. Since migrating oxide ions have attractive interactions with their surrounding La 6h ions, more expanded La 6h triangles lead to more energy costs for atomic displacements of the La 6h ions during the oxide-ion migration, resulting in their higher potential energy barriers. The effect of La 4f vacancies on the oxide-ion migration can be explained by such local atomic arrangements of La 6h and their interactions with migrating oxide ions.
•The conduction mechanism of oxide ions in lanthanum silicate apatite•The higher La vacancy contents, the higher potential barrier heights.•The higher La vacancy contents, the larger structural distortions of La ions.•The origin of increased potential barrier heights is the structural distortions.
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•Amorfrutin B was synthesized from amorfrutin A ethyl ester by a seven-step sequence.•(E)-Olefine of amorfrutin B was constructed by Johnson-Claisen rearrangement.•(S)- and ...(R)-amorfrutin D were synthesized both via CBS asymmetric reduction.
Synthesis of the geranylated dihydrostilbenoid amorfrutin B with antimicrobial, PPARγ modulating and quorum sensing inhibitory activities has been achieved from amorfrutin A ethyl ester by a seven-step sequence involving the Johnson–Claisen rearrangement to install the (E)-configured double bond on the side chain. The proposed stereoisomer of amorfrutin D and its enantiomer have been synthesized enantioselectively from the same starting material, both in nine steps, using the CBS asymmetric reduction as the key step.
A concise synthesis of cajaninstilbene acid was achieved in 7 steps from (E)-3,5-dimethoxystilbene in 8.6% overall yield via the Claisen rearrangement of an aryl reverse-prenyl ether as the key step. ...Cytotoxic activities against human pancreatic carcinoma PANC-1 cells of cajaninstilbene acid and amorfrutins A-D were also evaluated.
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