DMSO-Assisted K3 PO4 -Catalyzed Cooperative Metal-Free, Base-Free Etherification of Chloroheteroarenes at Low Temperature.

Etherification of chloroheteroarenes was performed at low temperatures under metal-free, ligand-free and base-free conditions, that is, the reaction is promoted by the cooperative effect of DMSO (solvent) as a promoter and K3 PO4 providing the catalytic surface (rather than a base). The protocol exhibits good substrate scope under mild reaction conditions and has also been explored mechanistically.

Rapid plugged flow synthesis of nucleoside analogues via Suzuki-Miyaura coupling and heck Alkenylation of 5-Iodo-2'-deoxyuridine (or cytidine).

Nucleosides modification via conventional cross-coupling has been performed using different catalytic systems and found to take place via long reaction times. However, since the pandemic, nucleoside-based antivirals and vaccines have received widespread attention and the requirement for rapid modification and synthesis of these moieties has become a major objective for researchers. To address this challenge, we describe the development of a rapid flow-based cross-coupling synthesis protocol for a variety of C5-pyrimidine substituted nucleosides. The protocol allows for facile access to multiple nucleoside analogues in very good yields in a few minutes compared to conventional batch chemistry. To highlight the utility of our approach, the synthesis of an anti-HSV drug, BVDU was also achieved in an efficient manner using our new protocol. Supplementary Information: The online version contains supplementary material available at 10.1007/s41981-023-00265-1.

Suzuki-Miyaura Coupling, Heck Alkenylation, and Amidation of DMTr-Protected 5-Iodo-2'-Deoxyuridine via Palladium-catalyzed Reactions.

Modification of nucleosides via cross-coupling processes has been carried out extensively on unprotected halonucleosides to produce functionalized nucleosides that are often developed for incorporation into oligonucleotides or used as fluorescent probes. This approach requires protection of the 5'-OH with the 4,4'-dimethoxytrityl (DMTr) group, which is complicated and a common cause of reaction failure. Here we report a method for direct functionalization of 5'-O-DMTr-5-iodo-2'-deoxyuridine via Suzuki-Miyaura cross-coupling, Heck alkenylation, and carboamidation. This approach facilitates rapid synthesis of a variety of C5-substituted 5'-O-DMTr-2'-deoxyuridine derivatives. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Synthesis of the SerrKap palladacycle complex Basic Protocol 2: Suzuki-Miyaura coupling of 5'-O-DMTr-5-iodo-2'-deoxyuridine using SerrKap palladacycle Basic Protocol 3: Heck coupling of 5'-O-DMTr-5-iodo-2'-deoxyuridine using SerrKap palladacycle Basic Protocol 4: Heck coupling of 5'-O-DMTr-5-iodo-2'-deoxyuridine with Ruth linker using Pd(OAc)2 /PTABS Basic Protocol 5: Carbonylative amidation of 5'-O-DMTr-5-iodo-2'-deoxyuridine using Pd(OAc)2 /PTABS.

Clinico-Radiological-Pathologic Profile and Outcomes of Lung Transplant in Post-COVID-19 Phenotype: A Single Center Experience.

BACKGROUND: Lung transplantation (LTx) has come as hope for select patients with post-COVID acute respiratory distress syndrome (ARDS). It has a different phenotype with unique challenges. We aimed to bring out our experience with and outcomes of LTx for post-COVID ARDS. METHODS: This study is retrospective case series from a single center in India. All the patients with post-COVID end stage lung disease (ESLD) who underwent bilateral LTx between 1st May 2020 and 30th August 2021 were included. LTx was performed following no improvement with optimal medical management with adequate time provided for recovery. Information relating to demographics, comorbidities, pretransplant status, perioperative parameters, gross and histopathological findings of explanted lungs, posttransplant morbidity, and mortality were analyzed. RESULTS: This study included 23 patients. The median age of the patients in this study was 42 years and 20 participants were men (87%). The mean duration of intensive care unit stay was 15.83 ± 6.61 days. Mortality was observed among 8 participants (34.78%). Mean survival time was 34.54 weeks. Among the 8 patients who expired, the cause of death was sepsis for 6 patients (75.0%), neurologic cerebrovascular accident for 1 patient (12.5%), and cytomegalovirus for 1 patient (12.5%). All the deaths were reported in primary graft dysfunction grade 2 & 3 category. No rejections were observed on first and third month surveillance biopsies. CONCLUSIONS: LTx is the definitive option for survival in select patients with severe post-COVID-19-associated ESLD. This study brings out various challenges involved in such phenotypes and also observations in postoperative recovery.

Quadrol-Pd(II) complexes: phosphine-free precatalysts for the room-temperature Suzuki-Miyaura synthesis of nucleoside analogues in aqueous media.

Commercially available Quadrol, N,N,N',N'-tetrakis(2-hydroxypropyl)ethylenediamine (THPEN), has been used for the first time as a N^N-donor neutral hydrophilic ligand in the synthesis and characterization of new water soluble palladium(II) complexes containing chloride, phthalimidate or saccharinate as co-ligands. [PdCl2(THPEN)] (1) [Pd(phthal)2(THPEN)] (2), [Pd(sacc)2(THPEN)] (3) and the analogous complex with the closely related N,N,N',N'-tetrakis(2-hydroxyethyl)ethylenediamine (THEEN) [Pd(sacc)2(THEEN)] (4) were efficiently prepared in a one-pot reaction from [PdCl2(CH3CN)2] or Pd(OAc)2. Structural characterization of 1 and 3 by single crystal X-ray diffraction produced the first structures reported to date of palladium complexes with Quadrol. The resultant palladium complexes are highly soluble in water and were found to be effective as phosphine-free catalysts for the synthesis of functionalized nucleoside analogues under room-temperature Suzuki-Miyaura cross-coupling conditions between 5-iodo-2'-deoxyuridine (& 5-iodo-2'-deoxycytidine) with different aryl boronic acids in neat water. This is the first report of the coupling process performed on nucleosides in water at room temperature.

Room temperature HFIP/Ag-promoted palladium-catalyzed C-H functionalization of benzothiazole with iodoarenes.

A versatile synthetic protocol involving the room temperature direct arylation of benzothiazole with a wide variety of iodoarenes under Ag-promoted Pd-catalyzed conditions in HFIP as the reaction solvent has been presented. A sequential HFIP-promoted selective iodination of arenes followed by Pd-catalyzed direct arylation of benzothiazole has also been disclosed. The utility of the developed protocol has been demonstrated by the synthesis of anti-tumor agents, PMX-610 and CJM-126 (precursor).

Room-Temperature Amination of Chloroheteroarenes in Water by a Recyclable Copper(II)-Phosphaadamantanium Sulfonate System.

Buchwald-Hartwig amination of chloroheteroarenes has been a challenging synthetic process, with very few protocols promoting this important transformation at ambient temperature. The current report discusses about an efficient copper-based catalytic system (Cu/PTABS) for the amination of chloroheteroarenes at ambient temperature in water as the sole reaction solvent, a combination that is first to be reported. A wide variety of chloroheteroarenes could be coupled efficiently with primary and secondary amines as well as selected amino acid esters under mild reaction conditions. Catalytic efficiency of the developed protocol also promotes late-stage functionalization of active pharmaceutical ingredients (APIs) such as antibiotics (floxacins) and anticancer drugs. The catalytic system also performs efficiently at a very low concentration of 0.0001 mol % (TON = 980,000) and can be recycled 12 times without any appreciable loss in activity. Theoretical calculations reveal that the π-acceptor ability of the ligand PTABS is the main reason for the appreciably high reactivity of the catalytic system. Preliminary characterization of the catalytic species in the reaction was carried out using UV-VIS and ESR spectroscopy, providing evidence for the Cu(II) oxidation state.

Challenges, experiences, and postoperative outcomes in setting up first successful lung transplant unit in India.

BACKGROUND: Lung transplantation (LT) has emerged as a definitive cure for a plethora of end-stage lung diseases (ESLDs). With improvements in immune-suppression protocols, the posttransplantation survival rates have gone up. AIM: The study reported the initial experience of the India's single largest lung transplant program on clinicopathological profile, procedures, challenges encountered, and outcomes. SETTINGS AND DESIGN: A retrospective analysis was done from data available at three centers of Institute of Heart and Lung Transplant, Gleneagles Global Hospitals across Chennai, Bengaluru, and Mumbai. MATERIALS AND METHODS: A total of 132 patients underwent lung (single or bilateral) or combined heart and lung transplant between April 2017 and March 2020. All the participants had 30 days' follow-up. Postoperative complications, graft rejection, and 30-day mortality were reported. Kaplan-Meier survival analysis and logistic regression analysis were performed. STATISTICAL ANALYSIS USED: Kaplan-Meier survival and binary logistic regression was performed. RESULTS: Interstitial lung diseases, 65.91%, were the most common diagnosis. Bilateral LT (81.3%) was the most common type of LT performed. Grade III primary graft dysfunction was observed in 16 (12.1%). Distal airway stenosis (21.97%) was the most common complication followed by anastomotic stenosis (14.30%). Gram-negative bacterial sepsis (52%) was the leading cause of death. Cumulative probability of survival at 1 month was 0.85 (95% confidence interval [CI] 0.80-0.92), and at 1 year, it was 0.78 (95% CI, 0.72-0.86). CONCLUSION: This study establishes the fact that despite multiple challenges, LT is a viable option for selected patients with ESLDs in India and should encourage early referrals to a transplant center.