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Within the large poly(3-hydroxyalkanoate) (PHA) family, C3 propionates are much less studied than C4 butyrates, with the exception of α,α-disubstituted propionate PHAs, particularly poly(3-hydroxy-2,2-dimethylpropionate), P3H(Me) 2 P, due to its high melting temperature ( T m ∼ 230 °C) and crystallinity (∼76%). However, inefficient synthetic routes to its monomer 2,2-dimethylpropiolactone [(Me) 2 PL] and extreme brittleness of P3H(Me) 2 P largely hinder its broad applications. Here, we introduce simple, efficient step-growth polycondensation (SGP) of a hydroxyacid or methyl ester to afford P3H(Me) 2 P with low to medium molar mass, which is then utilized to produce lactones through base-catalyzed depolymerization. The ring-opening polymerization (ROP) of the 4-membered lactone leads to high-molar-mass P3H(Me) 2 P, which can be depolymerized by hydrolysis to the hydroxyacid in 99% yield or methanolysis to the hydroxyester in 91% yield, achieving closed-loop recycling via both SGP and ROP routes. Intriguingly, the chain end of the SGP-P3H(Me) 2 P determines the depolymerization selectivity toward 4- or 12-membered lactone formation, while both can be repolymerized back to P3H(Me) 2 P. Through the formation of copolymers P3H(Me/R) 2 P ( R = Et, n Pr), PHAs with high tensile strength and ductility, coupled with high barriers to water vapor and oxygen, have been created. Notably, the PHA structure-property study led to P3H( n Pr) 2 P with a record-high T m of 266 °C within the PHA family.

The in silico evaluation of 11 H -pyrido[2,1- b ]quinazolin-11-one derivatives against SARS-CoV-2 RdRp was undertaken based on the reports on antiviral activities of this class of compounds in addition to the promising interactions of the antiviral drug penciclovir as well as quinazoline derivatives with SARS-CoV-2 RdRp in silico . The target compounds were prepared via an Ullmann-Goldberg type coupling followed by the subsequent cyclization (involving amidation) in a single pot. The methodology involved a CuI-catalyzed reaction of 2-iodobenzoate ester with 2-aminopyridine or quinolin-2-amine or thiazol-2-amine under ultrasound to give the expected products in acceptable (51-93%) yields. The molecular interactions of the synthesized 11 H -pyrido[2,1- b ]quinazolin-11-one derivatives with the SARS-CoV-2 RdRp (PDB: 7AAP) were evaluated in silico . The study suggested that though none of these compounds showed interactions better than penciclovir but the compound 3a and 3n appeared to be comparable along with 3b seemed to be nearly comparable to favipiravir and remdesivir. The compound 3n with the best binding energy (-79.85 Kcal/mol) participated in the H-bond interactions through its OMe group with THR556 as well as ARG624 and via the N-5 atom with the residue SER682. The in silico studies further suggested that majority of the compounds interacted with the main cavity of active site pocket whereas 3h and 3o that showed relatively lower binding energies (-66.06 and -66.28 Kcal/mol) interacted with the shallow cavity underneath the active site of SARS CoV-2 RdRp. The study also revealed that a OMe group was favourable for interaction with respect to its position in the order C-8 > C-1 > C-2. Further, the presence of a fused quinoline ring was tolerated whereas a fused thiazole ring decreased the interaction significantly. The in silico predictions of pharmacokinetic properties of 3a, 3b and 3n indicated that besides the BBB (Blood Brain Barrier) penetration potential these molecules may show a good overall ADME. Overall, the regioisomers 3a, 3b and 3n have emerged as molecules of possible interest in the context of targeting COVID-19., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Elsevier B.V. All rights reserved.)

Polyhydroxyalkanoates (PHAs) have attracted increasing interest as sustainable plastics because of their biorenewability and biodegradability in the ambient environment. However, current semicrystalline PHAs face three long-standing challenges to broad commercial implementation and application: lack of melt processability, mechanical brittleness, and unrealized recyclability, the last of which is essential for achieving a circular plastics economy. Here we report a synthetic PHA platform that addresses the origin of thermal instability by eliminating α-hydrogens in the PHA repeat units and thus precluding facile cis-elimination during thermal degradation. This simple α,α-disubstitution in PHAs enhances the thermal stability so substantially that the PHAs become melt-processable. Synergistically, this structural modification also endows the PHAs with the mechanical toughness, intrinsic crystallinity, and closed-loop chemical recyclability.

distribution of auxin within plant tissues is of great importance for developmental plasticity, including root gravitropic growth. Auxin flow is directed by the subcellular polar distribution and dynamic relocalisation of auxin transporters such as the PIN-FORMED (PIN) efflux carriers, which can be influenced by the main natural plant auxin indole-3-acetic acid (IAA). Anthranilic acid (AA) is an important early precursor of IAA and previously published studies with AA analogues have suggested that AA may also regulate PIN localisation. Using Arabidopsis thaliana as a model species, we studied an AA-deficient mutant displaying agravitropic root growth, treated seedlings with AA and AA analogues and transformed lines to over-produce AA while inhibiting its conversion to downstream IAA precursors. We showed that AA rescues root gravitropic growth in the AA-deficient mutant at concentrations that do not rescue IAA levels. Overproduction of AA affects root gravitropism without affecting IAA levels. Treatments with, or deficiency in, AA result in defects in PIN polarity and gravistimulus-induced PIN relocalisation in root cells. Our results revealed a previously unknown role for AA in the regulation of PIN subcellular localisation and dynamics involved in root gravitropism, which is independent of its better known role in IAA biosynthesis., (© 2019 The Authors. New Phytologist © 2019 New Phytologist Trust.)

Auxin phytohormones control most aspects of plant development through a complex and interconnected signaling network. In the presence of auxin, AUXIN/INDOLE-3-ACETIC ACID (AUX/IAA) transcriptional repressors are targeted for degradation by the SKP1-CULLIN1-F-BOX (SCF) ubiquitin-protein ligases containing TRANSPORT INHIBITOR RESISTANT 1/AUXIN SIGNALING F-BOX (TIR1/AFB). CULLIN1-neddylation is required for SCF TIR1/AFB functionality, as exemplified by mutants deficient in the NEDD8-activating enzyme subunit AUXIN-RESISTANT 1 (AXR1). Here, we report a chemical biology screen that identifies small molecules requiring AXR1 to modulate plant development. We selected four molecules of interest, RubNeddin 1 to 4 (RN1 to -4), among which RN3 and RN4 trigger selective auxin responses at transcriptional, biochemical, and morphological levels. This selective activity is explained by their ability to consistently promote the interaction between TIR1 and a specific subset of AUX/IAA proteins, stimulating the degradation of particular AUX/IAA combinations. Finally, we performed a genetic screen using RN4, the RN with the greatest potential for dissecting auxin perception, which revealed that the chromatin remodeling ATPase BRAHMA is implicated in auxin-mediated apical hook development. These results demonstrate the power of selective auxin agonists to dissect auxin perception for plant developmental functions, as well as offering opportunities to discover new molecular players involved in auxin responses., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)

Regio- and stereoselective addition of alkyl Grignard reagents to pyridine-N-oxides gave C2-alkylated N-hydroxy-1,2,5,6-tetrahydropyridines and trans-2,3-disubstituted N-hydroxy-1,2,5,6-tetrahydropyridines in good to excellent yields. These intermediates were aromatized or alternatively reduced in one-pot methodologies for efficient syntheses of alkylpyridines or piperidines, respectively. These reactions have a broad substrate scope and short reaction times.

A facile and rapid synthesis of isocoumarin derivatives using a copper-catalyzed tandem C-C/C-O coupling strategy from readily available substrates is described. The reactions of a wide range of 2-iodo-N-phenyl benzamides and acyclic diketones as starting materials were investigated.

We describe the utility of a Pd/C-Cu mediated method in the synthesis of 2,5-disubstituted indoles in water via a coupling-cyclization strategy. Further application of this methodology has been demonstrated in the preparation of a target indole derivative via a 7-step process the key step being the Pd/C-mediated coupling reaction.

Herein, we report transition metal-catalyzed intramolecular cyclization of o-(1-alkynyl)benzenesulfonamides to afford 3-substituted benzothiazines regioselectively via a C-N bond forming reaction and Cu-catalyzed sequential C-N and C-C bond formation leading to the corresponding 3,4-disubstituted derivatives.

A new one-pot reaction for the regioselective construction of a six-membered fused N-heterocyclic ring leading to isoquinolones under Pd/C-Cu catalysis is described.