Table 4 - uploaded by Sachin Popat Gholap
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Source publication
An efficient method for the selective removal of aryl silyl protection using NaH in DMF solvent is developed. The method is rapid, opera-tionally simple and can be carried out at room temperature. Excellent chemoselectivity and high yields of phenol products are other advantages of this method. A one-pot desilylation and reprotection as aryl alkyl...
Contexts in source publication
Context 1
... in situ reprotection with various groups giving aryl ethers and esters. Remarkably the one-pot desilylation and etherication or esterication proceeds in a short reaction time with good yields (Table 4). When we subjected the aryl OTBS compound 4c for one-pot TBS deprotection with NaH in DMF and then etherication with different groups (viz. ...
Context 2
... we subjected the aryl OTBS compound 4c for one-pot TBS deprotection with NaH in DMF and then etherication with different groups (viz. Me, Bn, MOM) and acylation, it delivered the corresponding ethers 8a-c and ester 8d in 30 to 35 min in good yields (Table 4, entries 1-4). The chemo- selective removal of only aryl silyl ether in 6f followed by one-pot etherication or esterication of phenol afforded the corresponding ethers 8e-i and ester 8j in excellent yields (entries 5-10). ...
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Citations
... Additionally, the unique hydrolytic reactivity of poly(silyl ether)s makes them attractive in many other applications [12] . Therefore, it has been a material of immense interest in the preparation of polymers based on silicon with respect to evaluate their biological activity [13] . ...
In this research, palm oil and soy oil were used as a natural polyol to prepare novel poly(silyl ether)s. Palm oil and soy oil were first converted to monoglyceride by one step via alcoholysis process in the presence of 0.1% CaO as a catalyst. The monoglycerides were characterized by Fourier transform infrared spectrometer (FT-IR), nuclear magnetic resonance (NMR) and iodine test. The novel poly(silyl ether)s were prepared via polycondensation reaction between dimethyldichlorosilane with monoglycerides based on palm and soy oils, respectively. FT-IR, NMR and silicone-29 (29Si NMR) were used to confirm and determine the presence of silicone in the synthesized polymers. Thermal behavior was studied by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Antibacterial activity of the polymers was screened against three different strains of bacteria, namely Escherichia coli E266, Staphylococcus aureus S276 and Salmonella choleeraesuis 10708.
... 26 We now report the first example of an organic TADF-based LEEC wherein the TADF material serves the dual role of charge transporter and emitter. Additionally, we also report doped and single-component spin-coated OLEDs, whose external quan-tum efficiencies are superior to those few previous reports of nondoped TADF OLEDs in the literature, 17,27,28 and contrast their performance to that of the LEEC. ...
Two novel charged organic thermally activated delayed fluorescence (TADF) emitters, 1 and 2, have been synthesized. Their TADF behavior is well-supported by the multiexponential decay of their emission (nanosecond and microsecond components) and the oxygen dependence of the photoluminescence quantum yields. Spin-coated electroluminescent devices have been fabricated to make light-emitting electrochemical cells (LEECs) and organic light-emitting diodes (OLEDs). The first example of a non-doped charged small organic molecule LEEC is reported and exhibited an external quantum efficiency (EQE) of 0.39% using 2. With a multilayer architecture, a solution-processed OLED device using neat 2 as the emitting layer gave an EQE of 5.1%, the highest reported to date for a nondoped solution-processed small molecule organic TADF OLED. These promising results open up a new area in light-emitting materials for the development of low-cost TADF LEECs.
The Gli transcription factors within the Hedgehog (Hh) signaling pathway play essential roles in human development. However, the reactivation of Gli proteins in adult tissue is tumorigenic and drives the progression of several cancers, including the majority of basal cell carcinomas. Here we describe a novel set of indolactam dipeptides that target protein kinase C (PKC), exploiting the unique capacity of PKC isozymes to act as regulators of Gli. We devised an efficient synthetic route for the indolactam-based natural product (-)-pendolmycin and a series of analogues, and we evaluated these analogues in mechanistically distinct Gli reporter assays. The lead compound from these studies, N-hexylindolactam V, exhibits superior Gli suppression relative to clinical inhibitors and blocks the growth of Gli-dependent basal cell carcinoma cells. More broadly, our structure-activity studies provide inroads for the development of novel Gli antagonists and new avenues for combating Gli-driven cancers.
Background
A new family of purine nucleoside cholinesterase inhibitors was disclosed by us, with potency and selectivity over acetylcholinesterase or butyrylcholinesterase controlled by tuning structural and stereochemical features of nucleosides with perbenzylated glycosyl moieties.
Objective
Design, synthesis and biological evaluation of new purine nucleosides to investigate glycon protecting group pattern required for anticholinesterase activity and selectivity.
Method
Regioselective chemistry to introduce methyl/benzyl groups in glycon donors and N-glycosylation to access the target nucleosides. Evaluation of their biological potential and selectivity as cholinesterase inhibitors.
Results
Synthetic strategies chosen resulted in high glycon donors overall yield and regio- and stereoselectivity was found in N-glycosylation reaction. Some of the new nucleosides are cholinesterase inhibitors and selectivity for butyrylcholinesterase was also achieved.
Conclusion
N-glycosylation reaction was stereoselective for the β-anomers while regioselectivity was achieved for the N9 isomers when glycon positions 2 and 3 were methylated. Cholinesterase inhibition was found when the 2,3-di-O-benzyl-4-O-methyl pattern is present in the sugar moiety. Amongst the new compounds, the two most promising ones showed micromolar inhibition (mixed inhibition), being one of them selective for butyrylcholinesterase inhibition.
In this paper, we present an unprecedented and general umpolung protocol that allows the functionalization of silyl enol ethers and of 1,3‐dicarbonyl compounds with a large range of heteroatom nucleophiles, including carboxylic acids, alcohols, primary and secondary amines, azide, thiols, and also anionic carbamates derived from CO2. The scope of the reaction also extends to carbon‐based nucleophiles. The reaction relies on the use of 1‐bromo‐3,3‐dimethyl‐1,3‐dihydro‐1λ³[d][1,2]iodaoxole, which provides a key α‐brominated carbonyl intermediate. The reaction mechanism has been studied experimentally and by DFT, and we propose formation of an unusual enolonium intermediate with a halogen‐bonded bromide.
To improve tumor selectivity, we prepared a new triple-targeting delivery system bearing two anticancer agents. Both anticancer agents in this system are released in the presence of both H 2 O 2 and cathepsin B which are highly produced in cancer cells.
Four-membered heterocycles such as oxetanes and azetidines represent a unique class of small, strained rings. These scaffolds are found in a variety of biologically active natural products and also function as important structural building blocks in pharmaceutical products due to their desirable pharmacokinetic properties. However, from a synthetic standpoint, four-membered heterocycles are often considered the most difficult to access in comparison to their smaller, three-membered, as well as their larger, five- and six-membered analogs. Thus, there is a strong demand for the development of new synthetic methods that allow for the synthesis of four-membered heterocycles in an efficient and practical fashion. The synthetic challenges in accessing four-membered rings are commonly associated with their high ring-strain, yet this inherent property provides these scaffolds with unique reactivity that can also be harvested in catalytic transformations. This dissertation discusses the development of new methods for the synthesis of azetidines relying on visible light photocatalysis, as well as investigations into the Lewis acid-catalyzed carbonyl–olefin metathesis reaction that utilizes oxetanes as reactive intermediates. The first chapter of this dissertation studies the divergent reactivity in Lewis acid-mediated transformations between carbonyls and olefins. Herein, it is demonstrated that relatively simple metal salts can achieve remarkable selectivity, resulting in either carbonyl–olefin metathesis or carbonyl–ene reaction products. Furthermore, parametrization of relevant reaction intermediates through DFT calculations allowed for the development of predictive statistical models that provide important insights into the observed divergent reactivity. The second and third chapter of this dissertation discuss the development of new methods for the synthesis of azetidines via visible light-mediated [2+2] cycloadditions. This strategy is advantageous over traditional approaches as it utilizes readily available oxime and alkene precursors that are reacted in a single, highly atom-economic transformation. A method for the synthesis of azetidines via an intramolecular [2+2] cycloaddition is reported herein that proceeds via triplet energy transfer from a commercially available iridium photocatalyst. This reaction utilizes substrates containing styrenes, which possess low triplet energies and are amenable to activation via energy transfer. This intramolecular strategy readily affords highly functionalized azetidine products, yet it cannot be translated into an intermolecular variant due to the limited excited state lifetime of styrenes. Therefore, a new method is presented that relies on 2-isoxazoline-3-carboxylates as a previously unexplored imine reagent. This class of compound can be activated via triplet energy transfer from an iridium photocatalyst to react with unactivated alkenes with high efficiency. This new intermolecular strategy complements the limitations of previous methods for the synthesis of azetidines, and provides facile access to previously inaccessible azetidine scaffolds.
Azodicarboxylate esters are common reagents in organic synthesis laboratories due to their utility in the Mitsunobu reaction. They can also be regarded as possible starting compounds for C–H functionalization, which up until now has been mainly achieved by transition-metal-catalyzed reactions. We have developed a novel reaction involving the quantitative coupling of 8-hydroxyquinoline or phenol with azodicarboxylate esters. The functionalization proceeds under mild base-catalyzed conditions selectively, and either the ortho-position of 8-hydroxyquinoline or para-position of the phenol/naphthol is involved in the reaction. This type of transformation can be considered as “hydrazo coupling” (by analogy with azo coupling). Herein, we discuss a plausible mechanism for this catalyzed substitution, backing up our findings with deuterium NMR experiments and by varying the starting compounds and bases. Using Boc-N=N-Boc as a substrate, we have developed the convenient and efficient synthesis of (8-hydroxyquinolin-7-yl)hydrazines, as well as demonstrating a new stereoselective route for the synthesis of medicinally important 4-hydroxyphenylhydrazine for laboratory use, which almost doubles the yield of the common industrial process and reduces the number of synthetic steps. A new “one-pot” procedure for the synthesis of aromatic 8-hydroxyquinolin-7-yl hydrazones was applied.
A metal-free, Brønsted acid, pTsOH-catalyzed intramolecular rearrangement of δ-hydroxyalkynones to substituted 2,3-dihydro-4H-pyran-4-ones has been developed. The rearrangement occurs with high regioselectivity under mild and open-air conditions. The scope of work has been illustrated by synthesizing an array of aliphatic and aromatic substituted 2,3-dihydro-4H-pyran-4-ones in upto 96% yield, 100% atom economy and complete regioselectivity. Some of the dihydropyranones are utilized for vinylic halogenations and to complete the total synthesis of bioactive natural products, obolactone and a catechol pyran isolated from Plectranthus sylvestris (labiatae).
