Protection Of Hydroxyl Groups Research Articles

Synthetic Studies toward (−)-Cleistenolide: Highly Stereoselective Synthesis of New γ-Lactone Subunits

This study describes the stereoselective synthesis of two new γ-lactones in 6 and 3 steps and 19 and 32% yield, respectively, directed toward the total synthesis of the natural product (−)-cleistenolide. The starting material was an enantiomerically pure diacetonide diol, derived from d-mannitol with the required stereocenters for (−)-cleistenolide synthesis. γ-Lactone syntheses were based on highly selective protection and deprotection of hydroxyls from d-mannitol. The formation of γ-lactone rings was the culmination of this approach, made possible by a Horner-Wadsworth-Emmons Z-olefination between diacetal aldehyde and ethyl 2-(bis(o-tolyloxy)phosphoryl)acetate to produce an unsaturated ester. The Z-isomer ester was highly favored in relation to the E-isomer (Z/E ratio of 94:6), allowing the formation of the γ-lactone ring under acid catalysis. This strategy precluded the use of chiral auxiliaries or catalysts for the control of stereocenters in the novel γ-lactones.

Synthesis of functional tetrathiafulvalene-terpyridine dyad for metal cation recognition

A new protected hydroxyl functionalized TTF derivative with an effective electronic communication between the TTF moiety and the Terpy unit for optical and electrochemical sensors.

Recent advances in catalytic silylation of hydroxyl‐bearing compounds: A green technique for protection of alcohols using Si–O bond formations

The development of catalytic silylation of alcohols under ambient reaction conditions plays an important role in organic synthesis. New silyl groups and methods for their introduction and removal are constantly being developed and offer chemists a wider range of options. In recent years, silyl protecting groups have been given expanded roles beyond their traditional use of temporarily rendering inactive alcohols. As silyl ether can be further converted to the parent alcohols in acidic conditions, silylation of alcohols can be regarded as an alternative method for hydroxyl protection under ambient reaction conditions. Merging the silyl protection/deprotection of alcohols with such modern methodologies, as green chemistry and nanoscience, has added additional value to these temporary components of synthetic intermediates. This review describes the historical background of the trimethylsilyl ethers preparation from alcohols using catalytic complexes and also the transformation of trimethylsilyl ethers into alcohol‐containing compounds via deprecation techniques.

Chemosystematic and evolutionary trends of the genistoid clade sensu stricto (Papilionoideae, Fabaceae)

The Papilionoideae, which comprises 503 genera and approximately 14,000 species, is the largest and most diverse subfamily of the Fabaceae family. In this subfamily, the Crotalarieae, Genisteae, Podalyrieae, Thermopsideae, Sophoreae and Euchresteae tribes are closely related by micro and macromolecular features, thus forming the genistoid clade. This group combines well-known genera, whereas other genera lack phytochemical and chemotaxonomic studies. Thus, this work aimed to characterize the special metabolites in these genera in order to define the chemical profile, the micromolecular markers and the chemical diversity, as well as to evaluate the group evolutionary trends. Flavonoids and alkaloids were identified as chemosystematic markers for the studied tribes due to high occurrence number and structural diversity. Among flavonoids, the flavones and isoflavones predominated. Low protection indexes of flavonoid hydroxyls by O-glycosylation or O-methylation were observed, whereas C-prenylation and C-glycosylation were frequent, mainly at C-6 and C-8 positions. The flavone/flavonol ratio shows the predominance of the flavones. Quinolizidine and piperidine alkaloids were present in most genera. Pyrrolizidine alkaloids were found in a few genera from Thermopsideae, Genisteae and Crotalarieae, which suggests a mechanism of adaptive convergence. Cluster analysis allowed separation of genera for each tribe by chemical similarities. The micromolecular trends of protection of flavonoid hydroxyls and alkaloid oxidation indicate the genistoid clade is through evolutionary transition, which is consistent with its phylogenetic position in the Papilionoideae subfamily.

Free volume manipulation of a 6FDA-HAB polyimide using a solid-state protection/deprotection strategy

Tert-butoxycarbonyl (t-BOC) is a thermally labile moiety that can be used to protect hydroxyl groups on polymers. In this study, t-BOC was appended onto a polyimide consisting of 2,2′-bis-(3,4-dicarboxyphenyl) hexafluoropropane dianhydride (6FDA) and 3,3′-dihydroxy-4,4′-diamino-biphenyl (HAB), after which the polymer was formed into self-standing films. Solid-state thermal treatments were performed to systematically remove t-BOC moieties to alter the physical packing structure and concomitant gas transport properties of the polymer. Despite performing deprotection reactions well below the glass transition temperature of 6FDA-HAB (~300 °C), this free volume manipulation (FVM) approach produced only subtle differences in polymer density, fractional free volume, average free volume element size, and gas transport properties relative to the unprotected polymer. While these findings suggest that thermally removing covalently bound functional groups from polymer films can be used to manipulate free volume and gas transport performance for glassy polymers, more robust polymer systems than linear polyimides are required to preserve the nascent free volume architecture generated from this approach.

Synthesis of Fluorescent Jasplakinolide Analogues for Live-Cell STED Microscopy of Actin.

The nanometer thickness of filaments and the dynamic behavior of actin—a protein playing a crucial role in cellular function and motility—make it attractive for observation with super-resolution optical microscopy. We developed the solution-phase synthesis of des-bromo-des-methyl-jasplakinolide-lysine, used as the “recognition unit” (ligand) for F-actin in living cells. The first amino acid—Fmoc-O-TIPS-β-tyrosine—was prepared in 78% yield (two steps in one pot). The new solution-phase synthesis involves 2-phenylisopropyl protection of the carboxyl group and does not require excesses of commercially unavailable amino acids. The overall yield of the target intermediate obtained in nine steps is about 8%. The 2-phenylisopropyl group can be cleaved from carboxyl with 2–3% (v/v) of TFA in acetonitrile (0–10 °C), without affecting TIPS protection of the phenolic hydroxyl in β-tyrosine and N-Boc protection in lysine. Des-bromo-des-methyl-jasplakinolide-lysine was coupled with red-emitting fluorescent dyes 580CP and 610CP (via 6-aminohexanoate linker). Actin in living cells was labeled with 580CP and 610CP probes, and the optical resolution measured as full width at half-maximum of line profiles across actin fibers was found to be 300–400 nm and 100 nm under confocal and STED conditions, respectively. The solution-phase synthesis of des-bromo-des-methyl-jasplakinolide-lysine opens a way to better fluorescent probe perspective for actin imaging.

Design, synthesis, brine shrimp lethality and cytotoxicity of some novel 17a-aza-D-homo-androster-17-one derivatives

In this work, twenty-eight novel 17a-aza-D-homo-androster-17-one derivatives, which divided into two categories, were synthesized with commercial available starting material (dehydroepiandrosterone) via oximation reaction, Beckmann rearrangement, hydroxyl protection, N-alkylation and deprotection. All compounds were characterized by 1H NMR, 13C NMR and HRMS. The structure of 14 g was also identified by X-ray single crystal diffraction. The bioactivities, brine shrimp toxicity and cytotoxicity, of all derivatives were tested. The results indicated that compounds 11 h, 11i, 11 m, 11 s, 14 b and 14 g exhibited excellent toxicity against brine shrimp with LC50 values ranging from 5.34 to 16.89 μg/mL, and compounds 11 s and 14 g displayed significant cytotoxicity against HT29 cells and A549 cells with IC50 values of 9.70 μM and 8.85 μM, respectively. Structure-activity relationships are discussed based on the results obtained from our research, and some important determinants for further modification of steroids towards the development of novel drug candidates are identified.

Synthesis of novel caffeic acid derivatives and their protective effect against hydrogen peroxide induced oxidative stress via Nrf2 pathway

AimThis study was aimed to synthesize novel caffeic acid derivatives and evaluate their potential applications for the treatment of oxidative stress associated disease. Main methodsCaffeic acid sulfonamide derivatives were synthesized by coupling sulfonamides to the backbone of caffeic acid and fully characterized by melting point test, FT-IR, MS, NMR, UV–vis and n-octanol–water distribution assay. Their free radical scavenging ability was evaluated using DPPH assay and cytotoxicity against A549 cells were determined by MTT assay. The protective effect of these derivatives against hydrogen peroxide (H2O2) induced oxidative injury was assessed in A549 cells from cell viability, production of reactive oxygen species (ROS) and malondialdehyde (MDA), alternation of antioxidase activities, and expressions of Nrf2 and its target genes. Key findingsSix novel caffeic acid sulfonamide derivatives were obtained. The derivatives showed better liphophilicity than the parent caffeic acid. CASMZ, CAST and CASQ exhibited similar DPPH scavenging capability as caffeic acid, while the protection of hydroxyl groups on the benzene ring with acetyl groups caused decrease in radical scavenging activity. No inhibitory effect on the proliferation of A549 cells were observed up to a concentration of 50 μM. Pre-treatment of cells with these derivatives strongly inhibited H2O2 induced decrease of cell viability, reduced the production of ROS and MDA, promoted antioxidase activities, and further upregulated the expression of Nrf2 and its target genes. SignificanceCaffeic acid sulfonamide derivatives were synthesized with simple reactions under mild conditions. They might protect cells from H2O2-induced oxidative injury via Nrf2 pathway.

Glycosylation on Unprotected or Partially Protected Acceptors

Over the last 30 years, there have been several methods developed for the synthesis of oligosaccharides, such as combinatorial synthesis, programmable one‐pot glycosylations, pre‐activation‐based chemo‐selective glycosylation strategy, random glycosylation, chemo‐enzymatic processes, and automated platforms. Distinguishing hydroxyl groups in carbohydrate monomers form the crux of oligosaccharides synthesis. The protection of hydroxyl groups stops glycosylation at undesired positions on carbohydrates, but additional steps are required to install and remove the protecting groups. The targeted functionalization of carbohydrates relies mostly on the protection of hydroxyl groups that are not supposed to undergo glycosylation and to leave the hydroxyl group unprotected where the glycosylation should occur. Numerous procedures to avoid or decrease protecting group manipulations have been developed for the synthesis of a single or an oligosaccharide library, such as glycosylation on unprotected or partially protected acceptors, and random glycosylation on unprotected acceptors. In this review, overall approaches for glycosylation on unprotected or partially protected acceptors in the synthesis of oligosaccharides and oligosaccharide libraries are summarized, the glycosylation on unprotected or partially protected carbohydrate acceptors with or without tin or boron mediation, and random glycosylation on unprotected or partially protected acceptors in solution phase or on solid phase are discussed.

Optimization of the Lipase-Catalyzed Selective Amidation of Phenylglycinol.

Ceramides and their analogs have a regulatory effect on inflammatory cytokines expression. It was found that a kind of ceramides analog synthesized from phenylglycinol could inhibit the production of cytokine TNF-α. However, two active hydrogen groups are present in the phenylglycinol molecule. It is difficult to control the process without hydroxyl group protection to dominantly produce amide in the traditional chemical synthesis. A selective catalytic the amidation route of phenylglycinol by lipases was investigated in this research. The results indicated that the commercial immobilized lipase Novozym 435 has the best regio-selectivity on the amide group. Based on the experimental results and in silico simulation, it was found that the mechanism of specific N-acyl selectivity of lipase was not only from intramolecular migration and proton shuttle mechanism, but also from the special structure of active site of enzyme. The optimal reaction yield of aromatic amide compound in a solvent-free system with lipase loading of 15 wt% (to the weight of total substrate) reached 89.41 ± 2.8% with very few of byproducts detected (0.21 ± 0.1% ester and 0.64 ± 0.2% diacetylated compound). Compare to other reported works, this work have the advantages such as low enzyme loading, solvent free, and high N-acylation selectivity. Meanwhile, this Novozym 435 lipase based synthesis method has an excellent regio-selectivity on most kinds of amino alcohol compounds. Compared to the chemical method, the enzymatic synthesis exhibited high regio-selectivity, and conversion rates. The method could be a promising alternative strategy for the synthesis of aromatic alkanolamides.

Antifungal Styryloquinolines as Candida albicans Efflux Pump Inhibitors: Styryloquinolines are ABC Transporter Inhibitors.

Styrylquinolines are heterocyclic compounds that are known for their antifungal and antimicrobial activity. Metal complexation through hydroxyl groups has been claimed to be a plausible mechanism of action for these types of compounds. A series of novel structures with protected hydroxyl groups have been designed and synthesized to verify the literature data. Their antifungal activity against wild-type Candida albicans strain and mutants with silenced efflux pumps activity has been determined. Combinations with fluconazole revealed synergistic interactions that were dependent on the substitution pattern. These results open a new route for designing active antifungal agents on a styrylquinoline scaffold.

Stereoselective Syntheses of 3'-Hydroxyamino- and 3'-Methoxyamino-2',3'-Dideoxynucleosides.

Aminonucleosides are used as key motifs in medicinal and bioconjugate chemistry; however, existing strategies toward 3′-hypernucleophilic amine systems do not readily deliver deoxyribo-configured products. We report diastereoselective syntheses of deoxyribo- and deoxyxylo-configured 3′-hydroxyamino- and 3′-methoxyamino-nucelosides from 3′-imine intermediates. The presence or absence of the 5′-hydroxyl-group protection dictates facial selectivity via inter- or intramolecular delivery of hydride from BH3 (borane). Protecting group screening gave one access to previously unknown 3′-methoxyamino-deoxyguanosine derivatives.

Phenacyl Xanthates: A Photoremovable Protecting Group for Alcohols under Visible Light

AbstractThe utility of phenacyl xanthates for the protection of hydroxyl groups is reported herein. Phenacyl xanthates are readily prepared via a one‐pot procedure, which employs the commercially available, inexpensive 2‐bromoacetophenone and carbon disulphide. The introduction of phenylcarboxymethyl dithiocarbonates could be achieved in good to excellent yield in the presence of ester group or ketal group. The hydroxyl group can be released in the presence of ethidine under irradiation of visible light without photocatalyst. The phenacyl xanthates could be selectively removed without affecting a series of common protecting groups, such as benzoate, tetrahydropyran and ketal groups. Finally, a plausible mechanism of photocleavage of phenacyl xanthates has been discussed.

Efficient synthesis of N- and O-linked glycopeptides using acid-labile Boc groups for the protection of carbohydrate moieties

Development of a synthetic method for the preparation of homogeneous glycopeptides and glycoproteins is important for the elucidation of their structures and functions. Here, we report on the concise and facile synthesis of glycopeptides using Boc groups for the protection of carbohydrate hydroxyl groups. This method enables us to remove the protecting groups from peptide and carbohydrate moieties in a single-step process without undesirable any side reaction.

Enantioselective Assembly of Tricyclic Tetrahydroquinoline Derivatives

AbstractA three‐step synthetic route towards enantioenriched tricyclic tetrahydroquinoline derivatives has been investigated. The first step involved the assembly of 4‐amino‐tetrahydroquinoline core through the asymmetric three‐component Povarov reaction of benzyl (E)‐prop‐1‐en‐1‐ylcarbamate and p‐anisidine with aliphatic aldehydes of various length bearing protected hydroxyl group. The alcohol was then deprotected and employed in an intramolecular reaction with a secondary amine of tetrahydroquinoline moiety producing desired tricyclic scaffolds.

Synthesis of Eugenyl Cinnamate from Clove Oil (Syzygium aromaticum) via Bromination-Dehydrobromination Methods

Synthesis of bioactive materials based on Indonesian natural products as precursors are potential to achieve a sustainable supply of modern medicines. Eugenyl cinnamate is a crucial building block in many bioactive compounds such as hepatoprotective silibinin. This research features simple synthesis of eugenyl cinnamate from eugenol, an essential oil presents as major constituent of clove oil (Syzygium aromaticum). The transformations were carried out via protection of hydroxyl group, bromination, and dehydrobromination reactions of eugenol (1) consecutively. The products of the synthesis were purified by gravity column chromatography and were characterized by FTIR and NMR spectroscopy. Benzylation of eugenol was carried out under basic condition with high yield (94.3%). Characterization by spectroscopic methods showed that eugenyl benzyl ether (2) was formed. Bromination of eugenyl benzyl ether yielded three products, namely: dibromo (3a and 3b), and tri-bromo eugenyl benzyl ether (3c). Compound 3a and 3b were epimers based on intensive NMR analysis (1H, 13C and DEPT). These epimers were separable using simple gravitational colomn chromatography. To improve the selectivity of the reaction, protecting group was changed to acetyl to yield eugenyl acetyl ether (4). Bromination of (4) yielded the desired dibromo product (5). The dehydrobromination reaction of compound 5 with cinnamic acid yielded the eugenyl cinnamate (6) with yield of 23.2%.

Synthesis of arborescent polystyrene by “click” grafting

ABSTRACTA method was developed for the synthesis of arborescent polystyrene by “click” coupling. Acetylene functionalities were introduced on linear polystyrene (Mn = 5300 g/mol, Mw/Mn = 1.05) by acetylation and reaction with potassium hydroxide, 18‐crown‐6 and propargyl bromide in toluene. Polymerization of styrene with 6‐tert‐butyldimethylsiloxyhexyllithium yielded polystyrene (Mn = 5200 g/mol, Mw/Mn = 1.09) with a protected hydroxyl chain end. Deprotection, followed by conversions to tosyl and azide functionalities, provided the side chain material. Coupling with CuBr and N,N,N′,N″,N″‐pentamethyldiethylenetriamine proceeded in up to 94% yield. Repetition of the grafting cycles led to well‐defined (Mw/Mn ≤ 1.1) polymers of generations G1 and G2 in 84% and 60% yield, respectively, with Mn and branching functionalities reaching 2.8 × 106 g/mol and 460, respectively, for the G2 polymer. Coupling longer (Mn = 45,000 g/mol) side chains with acetylene‐functionalized substrates was also examined. For a linear substrate, a G0 polymer with Mn = 4.6 × 105 g/mol and Mw/Mn = 1.10 was obtained in 87% yield; coupling with the G0 (Mn = 52,000 g/mol) substrate produced a G1 polymer (Mn = 1.4×106 g/mol, Mw/Mn = 1.38) in 28% yield. The complementary approach using azide‐functionalized substrates and acetylene‐terminated side chains was also investigated, but proceeded in lower yield. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1730–1740

An improved synthesis of latanoprost involving effective control on 15(S) diastereomer

An improved process for the synthesis of latanoprost having excellent optical purity (de 99.9%, [α]D20 = +35.37° (c = 0.90, acetonitrile)) without use of preparative HPLC is described. This process involves effective purification of hydroxyl intermediate (5A) through solvent crystallization followed by inhibition of inversion of the chiral center at C-15 position. This was possible due to judicious use of diol intermediate (6) for double bond reduction prior to hydroxyl protection.

Efficient Syntheses of Traumatic Lactone and Rhizobialide.

Herein, we report the total synthesis of traumatic lactone and rhizobialide by utilizing allenoic acid to construct the lactone ring. The key starting materials, allenoic acids, could be prepared by the ATA (allenation of terminal alkynes) of a terminal alkyne with an aldehyde that contained a protected hydroxyl group followed by hydrolysis. Importantly, the asymmetric synthesis could be realized just by replacing racemic diphenylprinol with (R)- or (S)-diphenylprinol to deliver the optically active allenoate.

Catalyst Free Hydroxyl Protection of Quinine via Esterification

A method to protect the hydroxyl group of quinine via esterification is developed. The method uses acetyl and benzoyl as the protection group. The method employs no catalyst that generates reasonable yield at 83% for acetyl and 73% for benzoyl. This catalyst free method emphasizes on the importance substrate reactivity to achieve free catalyst procedure. Ester form of quinine synthesized might be further functionalized for various aims in accordance to its rich functional group and building block of quinine.