Asymmetric Cascade Dearomatization-Cyclization Reaction of Tryptamines with ß,γ-Alkynyl-α-imino Esters: Access to Hexahydropyrrolo[2,3-b]indole-Containing Tetrasubstituted α-Amino Allenoates.

An organocatalytic enantio- and diastereoselective synthesis of hexahydropyrrolo[2,3-b]indole-containing tetrasubstituted α-amino allenoates, exhibiting both axial and central chirality, has been accomplished via cascade dearomatization-cyclization reaction. The γ-addition to ß,γ-alkynyl-α-imino esters provides a library of densely substituted highly enantioenriched allenes in high yields and excellent stereoselectivities. In addition, the scope of this methodology has been extended to tryptophol as well. A scale-up reaction and synthetic transformations of the products were performed to demonstrate the practical usefulness of this approach.

Enantioselective Aminative Dearomatization of Indoles via Electrophilic 1,6-Addition of p-Quinone Diimides (p-QDIs).

Herein we report the first use of p-quinone diimide for the aminative dearomatization of 2,3-disubstituted indoles to furnish C3 aza-quaternary chiral indolenines. This approach, which proceeds via an electrophilic 1,6-addition of p-quinone diimide, allows the synthesis of an array of optically active aza-quaternary indolenines with high yields and excellent enantioselectivities. A one-pot approach of the same has also been established to further improve the synthetic accessibility of this protocol.

Optical coherence tomography biomarkers DROL, PROS, SND, hyperreflective walls of foveal cystoid spaces as predictors of central macular thickness and visual acuity in diabetic macular edema treated with intravitreal ranibizumab.

PURPOSE: This study aims to establish DROL (disruption of retinal outer layers), PROS (photoreceptor outer segment length), SND (subfoveal neuroretinal detachment), and hyperreflective walls of foveal cystoid spaces (HRW) as optical coherence tomography (OCT) biomarkers and predictors of central macular thickness (CMT) and visual acuity in diabetic macular edema (DME) treated with intravitreal ranibizumab (IVR). METHODS: In this prospective, interventional study performed at a tertiary care center over a span of 1 year from December 2021 to December 2022, 50 eyes of 46 patients of DME were included. Visual acuity and spectral domain OCT imaging were performed at baseline. Using inbuilt calipers on SD-OCT, the horizontal extent of DROL and the vertical extent of PROS were measured manually. SND and HRW were assessed qualitatively. IVR was administered and patients were followed up at 4, 8, and 12 weeks. RESULTS: The eyes without DROL had statistically significant (P < 0.05) lesser CMT and better BCVA (best-corrected visual acuity) (P < 0.05) after pro re nata injection of IVR. There was a positive correlation between the extent of baseline DROL with final CMT (P < 0.05) and final logMAR BCVA (P > 0.05), whereas negative correlation with the extent of baseline PROS with final CMT (P < 0.05) and final logMAR BCVA (P > 0.05). The presence of HRW and SND predicted non-resolution of CMT and worse visual acuity after treatment with IVR in DME. CONCLUSION: DROL, PROS, SND, and hyperreflective walls of foveal cystoid spaces may be utilized as qualitative as well as quantitative biomarkers to predict the post-treatment CMT and visual acuity in DME.

Silver-Catalyzed Asymmetric Double Desymmetrization via Vinylogous Michael Addition of Prochiral α,α-Dicyanoalkenes to Cyclopentendiones.

An asymmetric double desymmetrization methodology has been developed for synthesizing densely functionalized chiral cyclopentylcyclohexane scaffolds. We have constructed four chiral centers, including an all-carbon quaternary stereocenter in a single C-C bond formation event. The methodology has high functional-group tolerance and delivers a broad range of enantioenriched products. This vinylogous Michael addition reaction of prochiral α,α-dicyanocyclohexane to 2,2-disubstituted cyclopentene-1,3-dione is catalyzed by a chiral Ag-(R)-DTBM-SEGPHOS catalyst.

Comparison of cosmesis, mydriasis, fundus visibility, and anterior chamber depth following single-pass four-throw pupilloplasty in congenital and traumatic iris defects.

PURPOSE: To compare postoperative cosmesis, mydriasis, fundus visibility, and anterior chamber depth (ACD) in congenital and traumatic iris defects after single-pass four-throw pupilloplasty (SFTP). SETTINGS AND DESIGN: Hospital-based non-randomized interventional study. METHODS: SFTP was done along with phacoemulsification in six patients each with congenital and traumatic iris defects, and the patients were followed for a minimum period of 3 months. The postoperative pupil shape, size, mydriasis, and ACD were compared between the two groups. RESULTS: Tissue approximation was successful in 11 out of 12 patients (91.7%), whereas it failed to do so in one patient with traumatic iris tear (8.3%). A central round pupil was attained in all six patients with congenital defects (group 1), whereas in the traumatic group (group 2), a central round pupil was attained in four cases. Group 1 did not show a significant reduction in horizontal pupil diameter, but group 2 had a significant reduction in pupil diameter postoperatively. Mydriasis and fundus visibility were satisfactory in all cases. There was a significant deepening of ACD in both groups. CONCLUSION: Traumatic mydriasis usually requires SFTP at two opposite poles to achieve a central pupil with a significant reduction in pupil size, whereas congenital coloboma requires SFTP to be done at the site of coloboma with occasional enlargement at the opposite pole if the pupil is eccentric.

Organocatalytic Asymmetric Cascade Michael-Acyl Transfer Reaction between 2-Fluoro-1,3-diketones and 2-Hydroxynitrostyrenes.

An organocatalytic asymmetric cascade Michael-acyl transfer reaction of 2-hydroxynitrostyrenes and monofluorinated ß-diketones has been developed employing a cooperative catalytic system. A combination of quinine-derived bifunctional squaramide catalyst and achiral hydrogen bond donor cocatalyst was found to be the most effective for this reaction and provided the fluorinated acyl transfer products in high yields with good diastereo- and excellent enantioselectivities. Synthetic transformations have been demonstrated, including the synthesis of functionalized 2,3-dihydrobenzofurans and 1-pyrroline.

Enantioselective Synthesis of Thiazolopyran Derivatives via a Direct Vinylogous Michael-oxa-Michael Sequence.

An efficient diastereo- and enantioselective direct vinylogous Michael-oxa-Michael sequence between 5-alkenyl thiazolones and isopropylidene oxindoles has been developed. The reaction is catalyzed by a bifunctional squaramide catalyst that allows to access a wide range of densely substituted thiazolopyran derivatives containing a quaternary stereocenter. This protocol is flexible toward different sterically and electronically tuned substrates and is amenable to gram-scale synthesis and several synthetic transformations.

Synthesis of Spiroisoindolinones via Ru(II)-Catalyzed Spiroannulation of N-Acyl Ketimines with Aryl Isocyanates/Isothiocyanates through Aromatic C-H Bond Activation.

Herein, we disclose the first report on Ru(II)-catalyzed amidation/thioamidation of 3-hydroxy-3-arylisoindolinones with isocyanates/isothiocyanates, respectively. The reaction furnishes spiroisoindolinones via sequential C-H functionalization of ortho C-H bond followed by intramolecular cyclization in moderate to high yields (up to 94%). Moreover, the developed strategy is highly atom-economical and site-selective and shows diverse substrate generality. Also, synthesized spiroisoindolinones undergo several chemical transformations.

Extended depth of focus intraocular lens versus a new monofocal intraocular lens: A prospective comparative and interventional study.

PURPOSE: To compare the visual outcome findings between a new monofocal intraocular lens (IOL) (Tecnis Eyhance) and extended depth of focus (EDOF) IOL (Appasamy Supraphob Infocus). METHODS: This prospective comparative interventional study evaluated 31 patients after implantation of Tecnis Eyhance (15 patients) and Supraphob EDOF IOL (16 patients). The uncorrected and corrected distance and intermediate and near visual acuity were measured at postoperative day 1, 1 week, 4 week, and 3 months. Contrast sensitivity, incidence of halos and glares, and patient satisfaction were assessed at 3 months postoperatively. RESULTS: The Tecnis Eyhance (n = 15) and Supraphob EDOF (n = 16) group were comparable with respect to all preoperative parameters including biometry, visual acuity, and cataract status. The average age distribution of participants was 56 ± 6 years. Postoperatively, both groups had similar distance and intermediate vision, but the near vision was significantly better in the EDOF group (P < 0.01) as compared to Tecnis Eyhance at 3 months. The contrast sensitivity and patient satisfaction were similar in both the groups. The incidence of halos and glares was present in the EDOF group, but it was statistically insignificant. CONCLUSION: The Tecnis Eyhance and Supraphob EDOF both were effective in improving distance and intermediate vision, but the near vision was significantly better in the EDOF group. Both the groups retained good contrast sensitivity and the majority of patients were satisfied.

Organocatalytic Asymmetric Direct Vinylogous Michael Initiated Ring Closure Reaction of 4-Nitroisoxazole Derivatives to 3-Isopropylidene Oxindoles.

Herein, we present the first ever use of 3-isopropylidene oxindoles as electrophiles in vinylogous Michael initiated ring closure reaction (MIRC). Among the various alkylidene oxindoles used in enantioselective spirocyclization reactions, isopropylidene oxindoles are the least explored to date. The competing reactivity of isopropylidene oxindoles (electrophilicity vs nucleophilicity) in the presence of a chiral organocatalyst is controlled by the logical selection of a more reactive nucleophile. The methodology produces a library of densely substituted highly enantioenriched spirocyclopropyl oxindoles with excellent yield and stereoselectivities. Moreover, the first enantioselective synthesis of HIV-1 NNRT inhibitor indicates the importance of our synthesized spiro-cyclopropyl oxindole core.

Chiral Phosphoric Acid-Catalyzed Asymmetric Friedel-Crafts Addition of Indolizine to Cyclic N-Sulfonyl Imine.

A highly efficient chiral phosphoric acid-catalyzed enantioselective Friedel-Crafts addition of indolizine to cyclic N-sulfonyl imine has been established. The newly developed protocol, which probably proceeds via a monoactivation reaction pathway, allows the access of enantioenriched sulfonamide functionalized indolizines with excellent yields (up to 99%) and enantioselectivities (up to 99%). Moreover, the synthetic utility of this protocol has been explored with some chemical transformations.

Enantioselective Dearomative [4+2] Cycloaddition Reaction of 1-Naphthols with In-Situ Generated ortho-Quinone Methides.

We disclose a catalytic, enantioselective dearomative reaction of non-functionalized 1-naphthols, which poses a synthetic challenge to organic chemists because of the relative ease of rearomatization via the elimination of a proton. In this work, the direct dearomatization of non-functionalized 1-naphthols was achieved through a chiral phosphoric acid (CPA) catalyzed enantioselective dearomative [4+2] cycloaddition reaction with in-situ generated ortho-quinone methides (o-QMs). The reported convergent method allows the use of readily available simple 1-naphthols without pre-functionalization, furnishing a variety of naphthopyran derivatives in good yields (up to 96 %) and moderate to excellent enantioselectivities (up to >99 % ee) under mild reaction conditions. The observed regio-, diastereo-, and enantioselectivities are the keys to the success of the current strategy utilizing o-QM as a diene surrogates, in combination with CPA catalysis.

Kinetic Resolution of Electron-Deficient Bromohydrins via Copper(II)-Catalyzed C-C Bond Cleavage.

Herein, we report a nonenzymatic kinetic resolution (KR) of α,ß-unsaturated ketone-derived bromohydrins (up to s = 211) with N-bromosuccinimide (NBS) in the presence of a chiral Cu(II)-Box catalyst via the C-C bond cleavage of the fast reacting enantiomer. A one-pot synthesis-KR approach of the same has also been realized with excellent enantioselectivities (up to 99% ee). Both protocols are found to be effective for a variety of substrates, leading to enantioenriched bromohydrins. The synthetic utility of this process has been demonstrated by exploring a new strategy to convert the resolved enantiomer to an optically active epoxide.

The Comparison of Dexmedetomidine to Dexamethasone as Adjuvants to Bupivacaine in Ultrasound-Guided Infraclavicular Brachial Plexus Block in Upper Limb Surgeries.

Background The clinical utility of adjuvants with local anesthesia produces an excellent nerve block with prolonged duration and faster onset. Brachial plexus block is widely used nowadays in patients undergoing upper limb surgery There are several approaches to achieve brachial plexus block such as interscalene, supraclavicular, infraclavicular, and axillary. The objective of this study is to compare the effectiveness of dexamethasone to dexmedetomidine as adjuvants to bupivacaine in patients undergoing ultrasound-guided infraclavicular brachial plexus (USG-ICBP) block. Methods A randomized, prospective, double-blind study was undertaken on the patients posted for upper limb surgeries under ultrasound-guided infraclavicular brachial plexus block. Sixty patients with the American Society of Anesthesiologists (ASA) classes I and II were randomly allocated into two groups. Group A received 25 mL of 0.5% bupivacaine and 1.5 mL (6 mg) of dexamethasone, and group B received 25 mL of 0.5% bupivacaine and 0.75 mL (75 mcg) of dexmedetomidine along with 0.75 mL of 0.9% normal saline (NS). Student's t test or Mann-Whitney test and chi-square test were used for statistical analysis. Results The onset of sensory block was significantly faster in the patients in group B as compared to the patients in group A. In terms of the duration of the block, sensory and motor blocks were maintained for a significantly longer duration in the group A patients as compared to those in group B. Moreover, the duration of postoperative analgesia was significantly longer-lasting in the group A patients. In terms of adverse effects, procedure-related complications such as the failure of the block and inadequate block were comparable across the groups. However, drug-related adverse effects were significantly more common in group B. Conclusion As compared to 75 mcg of dexmedetomidine, the addition of 6 mg of dexamethasone as adjuvant to 25 mL of 0.5% bupivacaine resulted in significantly longer-lasting sensory and motor blocks, postoperative analgesia, and a delayed time for first rescue analgesia without increasing undue adverse effects. Dexmedetomidine use is associated with more sedation as compared to dexamethasone.

Central-to-Axial Chirality: Asymmetric Organocatalytic Synthesis of Axially Chiral Chalcones via Exocyclic Dihydronaphthalenes.

Asymmetric synthesis of an unprecedented exocyclic dihydronaphthalene and an axially chiral naphthalene chalcone has been disclosed. Good to excellent asymmetric induction is achieved. The success is attributed to the unusual formation of exocyclic dihydronaphthalene, which plays a crucial role in ensuring axial chirality. This is the first report of exocyclic molecules capable of enabling the synthesis of axially chiral chalcones via stepwise asymmetric vinylogous domino double-isomerization using secondary amine catalysis.

Copper-Catalyzed Asymmetric Propargylic [3 + 2] Cycloaddition: Synthesis of Enantioenriched Dihydrofuro[3,2-c]coumarins and its Quinolinone and Thiocoumarin Analogues.

A copper(II)-P,N,N-ligand catalyzed propargylic [3 + 2] cycloaddition approach for the synthesis of optically enriched dihydrofuro[3,2-c]coumarins has been accomplished for the first time. The cycloaddition utilizes propargylic esters as C2-bis-electrophiles and 4-hydroxycoumarin derivatives as C,O-bis-nucleophiles. In addition, this novel strategy was also explored with 4-hydroxy-2-quinolinones and 4-hydroxythiocoumarins. Moreover, various dihydrofuro[3,2-c]coumarins and their quinolinone and thiocoumarin analogues were synthesized in moderate to good yields with high enantioselectivities.

Brønsted Acid Catalyzed Friedel-Crafts Alkylation of Naphthols with In Situ Generated Naphthol-Derived ortho-Quinone Methides: Synthesis of Chiral and Achiral Xanthene Derivatives.

We disclose herein an enantioselective protocol for the Brønsted acid catalyzed addition of naphthols to in situ generated naphthol-derived ortho-quinone methides (o-QMs) followed by intramolecular cyclization, which delivers substituted chiral xanthene derivatives, in a one-pot reaction sequence under mild conditions. This process serves to convert naphthol-derived ortho-hydroxyl benzylic alcohols into reactive naphthol-derived o-QMs using a chiral phosphoric acid (CPA) catalyst. Moreover, it is helpful in controlling the enantioselectivity of the carbon-carbon bond-forming event via hydrogen-bonding followed by intramolecular cyclization. Additionally, for the first time, we observe a Brønsted acid catalyzed C(sp2)-C(sp3) bond cleavage of naphthol-derived ortho-hydroxyl benzylic alcohols for the synthesis of achiral xanthene (sigma plane containing) derivatives in good to excellent yields.

COVID-19-Associated Rhino-orbital mucormycosis: Presentation and outcome.

We are reporting four accounts of rhino-orbital mucormycosis in patients during and after recovery from SARS-CoV-2 infection. The patients were diagnosed and treated for COVID-19 according to the current treatment protocols, following which they presented with sudden proptosis, ophthalmoplegia, and conjunctival injection, confirmed by magnetic resonance imaging and histopathological examination. The patients were treated with intravenous liposomal amphotericin B, and the outcome was observed. Early diagnosis and prompt intervention can substantially reduce the morbidity and mortality rates in these patients.

Asymmetric Synthesis of Spiro-3,3'-cyclopropyl Oxindoles via Vinylogous Michael Initiated Ring Closure Reaction.

A novel organocatalytic cascade approach for the synthesis of spiro-cyclopropyl oxindole derivatives has been developed. The methodology is based on asymmetric vinylogous Michael addition of 4-nitroisoxazole derivatives to N-Boc isatylidene malonates followed by intramolecular alkylation. Its remarkable stereocontrol, wide substrate scope, and scalability highlight this new developed strategy. Moreover, this work represents the first example of vinylogous Michael initiated ring closure (MIRC) reaction for the synthesis of chiral 3,3'-cyclopropyl oxindole.