Synthesis of an Immunologically Active Heptamannoside of Mycobacterium tuberculosis by the [Au]/[Ag]-Catalyzed Activation of Ethynylcyclohexyl Glycosyl Carbonate Donor.

Tuberculosis (TB) is one of the most dreadful diseases, killing more than 3 million humans annually. M. tuberculosis (MTb) is the causative agent for TB and has a thick and waxy cell wall, making it an attractive target for immunological studies. In this study, a heptamannopyranoside containing 1 → 2 and 1 → 6 α-mannopyranosidic linkages has been explored for the immunological evaluations. The conjugation-ready heptamannopyranoside was synthesized by exploiting the salient features of recently discovered [Au]/[Ag]-glycosidation of ethynylcyclohexyl glycosyl carbonate donors. The glycan was conjugated to the ESAT6, an early secreted protein of MTb for further characterization as a potential subunit vaccine candidate.

Regioselective ortho halogenation of N-aryl amides and ureas via oxidative halodeboronation: harnessing boron reactivity for efficient C-halogen bond installation.

The installation of the C-halogen bond at the ortho position of N-aryl amides and ureas represents a tool to prepare motifs that are ubiquitous in biologically active compounds. To construct such prevalent bonds, most methods require the use of precious metals and a multistep process. Here we report a novel protocol for the long-standing challenge of regioselective ortho halogenation of N-aryl amides and ureas using an oxidative halodeboronation. By harnessing the reactivity of boron over nitrogen, we merge carbonyl-directed borylation with consecutive halodeboronation, enabling the precise introduction of the C-X bond at the desired ortho position of N-aryl amides and ureas. This method offers an efficient, practical, and scalable solution for synthesizing halogenated N-heteroarenes under mild conditions, highlighting the superiority of boron reactivity in directing the regioselectivity of the reaction.

Boron-Mediated Regioselective Aromatic C-H Functionalization via an Aryl BF2 Complex.

An efficient regioselective functionalization of 2-aryl-heteroarenes and aryl aldehydes via an azaaryl BF2 complex has been developed. Mechanistically the reaction comprises fluoride to bromide ligand exchange on an aryl boron species and consecutive C-B bond cleavage to deliver a broad range of functionalized products. The reaction is high yielding, has a broad substrate scope where several different heteroarenes can be functionalized with chloro, bromo, iodo, hydroxyl, amine and BF2 in a highly regioselective fashion. The method can be applied for late-stage functionalization or for rapid skeleton remodeling with for instance cross-couplings.

Minimally invasive vaginal approach to the uterovestibular anastomosis for cervicovaginal aplasia: a case series and review of literature.

BACKGROUND: Congenital cervicovaginal agenesis (CVA) with functioning endometrium is an extremely rare mullerian anomaly. Genital tract patency and fertility preservation are the major challenges in cases of CVA. With the advances in surgical techniques, management has shifted from a radical approach-like hysterectomy towards a more conservative approach of uterine conservation. CASE PRESENTATION AND REVIEW OF THE LITERATURE: In the present study, we report our experience in managing four cases of congenital CVA with complete vaginal atresia, which were treated with a simple minimally invasive vaginal approach for UVA without using graft for neovagina creation and studied the long-term anatomic and functional result of uterovestibular anastomosis (UVA) in patients with CVA. A literature review was performed for congenital complete vaginal atresia (≤ 2 cm blind vagina), with a functioning uterus. The experience and results of this 4-year study are in accordance with the prior studies with 97% (33/34) success rate, where vestibular mucosa was used for the UVA. CONCLUSIONS: Findings of this study should encourage more gynaecologists to learn and recreate a complete vaginal approach, as no special surgical equipments are needed. Hysterectomy should only be reserved for cases, where repeated anastomosis attempts fail. This minimally invasive technique should be preferred over canalization procedures and graft, as it is associated with a higher success rate with least complications and recurrence. Conservative end-to-end anastomosis with a completely vaginal approach should be offered as the primary treatment option for CVA with total vaginal atresia.

Preparedness, administrative challenges for establishing obstetric services, and experience of delivering over 400 women at a tertiary care COVID-19 hospital in India.

OBJECTIVE: To provide a descriptive account of the challenges and administrative preparedness for establishing and sustaining safe obstetric services during the COVID-19 pandemic at Topiwala National Medical College & BYL Nair Charitable Hospital (NH), Mumbai, India. METHODS: The management of pregnant women with COVID-19 was implemented as per international (WHO, RCOG, ACOG) and national (Indian Council of Medical Research) recommendations and guidelines at an academic, tertiary care, COVID-19 hospital in India. RESULTS: Using a multidisciplinary approach and active engagement of a multispecialty team, obstetric services were provided to over 400 women with laboratory-confirmed COVID-19. A sustainable model is established for providing services to pregnant women with COVID-19 in Mumbai Metropolitan Region, India. CONCLUSION: With limited resources, it is possible to set up dedicated maternity services, aligned to international guidelines, for safe pregnancy outcomes in COVID-19 settings. This COVID-19 hospital addressed the challenges and implemented several known and novel methods to establish and sustain obstetric services for women with COVID-19. The model established in the present study can be replicated in other low- and middle-income countries.

Oxone promoted dehydrogenative Povarov cyclization of N-aryl glycine derivatives: an approach towards quinoline fused lactones and lactams.

Oxone promoted intramolecular dehydrogenative imino Diels-Alder reaction (Povarov cyclization) of alkyne tethered N-aryl glycine esters and amides has been explored, thus affording biologically significant quinoline fused lactones and lactams. The reaction is simple, scalable, and high yielding (up to 88%). The method was further extended to prepare biologically important luotonin-A analogues and the quinoline core of uncialamycin.

Accessing α-Arylated Nitriles via BF3·OEt2 Catalyzed Cyanation of para-Quinone Methides Using tert-Butyl Isocyanide as a Cyanide Source.

BF3·OEt2 catalyzed 1,6-conjugate addition of tert-butyl isocyanide to para-quinone methides and fuchsones for the synthesis of α-diaryl and α-triaryl nitriles has been reported. This protocol allows α-diaryl- and α-triaryl nitriles to be accessed in good to excellent yields and with a broad substrate scope, which could be further functionalized to give a versatile set of products. This is the first example wherein tert-butyl isocyanide has been used as a cyanide source for the 1,6-conjugate addition.

Expedient synthesis of the heneicosasaccharyl mannose capped arabinomannan of the Mycobacterium tuberculosis cellular envelope by glycosyl carbonate donors.

The global incidence of tuberculosis is increasing at an alarming rate, and Mycobacterium tuberculosis (Mtb) is the causative agent for tuberculosis, a disease with high mortality. Lipoarabinomannan (LAM) is one of the major components of the Mtb cellular envelope and is an attractive scaffold for developing anti-tubercular drugs, vaccines and diagnostics. Herein, a highly convergent strategy is developed to synthesize heneicosasaccharyl arabinomannan for the first time. The arabinomannan synthesized in this endeavour has several 1,2-trans or α-Araf linkages and three 1,2-cis or ß-Araf linkages end capped with 1,2-trans or α-Manp linkages. All the key glycosidations were performed with alkynyl carbonate glycosyl donors under [Au]/[Ag] catalysis conditions, which gave excellent yields and stereoselectivity even for the reactions between complex and branched oligosaccharides. The resultant allyl oligosaccharide was globally deprotected to obtain the heneicosasaccharyl arabinomannan as a propyl glycoside. In summary, heneicosasaccharyl mannose capped arabinomannan synthesis was achieved in 56 steps with 0.016% overall yield.

[Au]/[Ag]-catalysed expedient synthesis of branched heneicosafuranosyl arabinogalactan motif of Mycobacterium tuberculosis cell wall.

Emergence of multidrug-resistant and extreme-drug-resistant strains of Mycobacterium tuberculosis (MTb) can cause serious socioeconomic burdens. Arabinogalactan present on the cellular envelope of MTb is unique and is required for its survival; access to arabinogalactan is essential for understanding the biosynthetic machinery that assembles it. Isolation from Nature is a herculean task and, as a result, chemical synthesis is the most sought after technique. Here we report a convergent synthesis of branched heneicosafuranosyl arabinogalactan (HAG) of MTb. Key furanosylations are performed using [Au]/[Ag] catalysts. The synthesis of HAG is achieved by the repetitive use of three reactions namely 1,2-trans furanoside synthesis by propargyl 1,2-orthoester donors, unmasking of silyl ether, and conversion of n-pentenyl furanosides into 1,2-orthoesters. Synthesis of HAG is achieved in 47 steps (with an overall yield of 0.09%) of which 21 are installation of furanosidic linkages in a stereoselective manner.

p-Nitrophenyl carbonate promoted ring-opening reactions of DBU and DBN affording lactam carbamates.

The amidine bases DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) and DBN (1,5-diazabicyclo[4.3.0]non-5-ene) display nucleophilic behaviour towards highly electrophilic p-nitrophenyl carbonate derivatives with ring opening of the bicyclic ring to form corresponding substituted ε-caprolactam and γ-lactam derived carbamates. This simple method presents a unified strategy to synthesize structurally diverse ε-caprolactam and γ-lactam compounds with a large substrate scope.

Synthesis of D-fructose-derived spirocyclic 2-substituted-2-oxazoline ribosides.

The TMSOTf-mediated synthesis of ß-configured spirocyclic 2-substituted-2-oxazoline ribosides was achieved using a "Ritter-like" reaction in toluene through nucleophilic addition of electron-rich nitriles to the oxacarbenium ion intermediate of 1,2;3,4-di-O-isopropylidene-ß-D-psicofuranose derivatives with concomitant intramolecular trapping of the C2 hydroxymethyl group on the electrophilic nitrilium carbon. These carbohydrate-derived spirooxazolines are stable and were obtained in good yield with high stereoselectivity due to the conformational rigidity imparted by the 3,4-isopropylidene group.

Caesarean section under local anaesthesia: back to basics.

Caesarean section under local anaesthesia (CSLA) was performed on a patient with a diagnosis of gravida 2 para 1 living 1, with eight months amenorrhea and uncontrolled, refractory, complicated eclampsia with intrauterine fetal demise and a previous lower segment Caesarean section. As she was at very high risk (ASA Grade III) for main stream anaesthesia, i.e. general/regional, lidocaine (0.5%) was used. CSLA should not be seen as a primitive/retrograde step. Instead, it should be considered to be a life-saving procedure, especially for women in rural India. Anaesthetists are not dispensable but with them on standby one can avoid mainstream anaesthesia complications in high-risk patients.

Modified extraperitoneal Caesarean section: clinical experience.

The objective of the study was to study postoperative progress of modified extraperitoneal Caesarean section (MECS) technique (group A) and its comparison with standard transperitoneal Caesarean section (TCS) (group B). It is a prospective observational study with sample sizes of 93 and 105 for groups A and B, respectively, in the settings of Lokmanya Tilak Municipal Medical College and General Hospital, Mumbai, India, which see over 10,000 deliveries per annum. Five parameters were studied. Postoperative febrile morbidity was significantly lower in group A than in group B (6.5% versus 21%; P = 0.004). Gastrointestinal function recovery occurred earlier in group A than B (6 h versus 18.5 h; P < 0.01). Although the difference between skin incision to baby delivery time was significant (6.0 min versus 3.1 min; P < 0.01), there was no significant difference in Apgar score at 1 min (P = 0.3). There was no difference in intraoperative complications in two groups. MECS is associated with less febrile morbidity and early postoperative recovery than TCS.