Beyond Birth Work: Addressing Social Determinants of Health With Community Perinatal Support Doulas.

Adverse maternal and infant health outcomes among African Americans are increasingly recognized as indicators of a critical public health crisis in the United States. Research has found that stress is related to structural racism and the social determinants of health (SDOH) that cause avoidable, unfair inequities in resources, education, power, and opportunities across ethnic groups. This paper describes the SDOH needs and experiences of pregnant Black women from the perspective of doulas and Birthing Beautiful Communities (BBC) clients. The design was a qualitative description, using data collected over time (2017-2018, 2020-2021, and 2023). This study took place in Cleveland and Akron, Ohio and the sample included 58 clients, 26 doulas, and 2 resource intake specialist assistants (RISAs). Qualitative data included individual client interviews, three doula focus groups, and one interview with two BBC RISAs. Three coders used content analysis to deductively identify SDOHs and calculate the number of interviews that contained information about specific SDOHs. Although the sample reported issues with all SDOH, particular ones caused a cascade of SDOH effects. Transportation issues, for example, impeded women from being able to make it to work, doctor's appointments, and to purchase essential baby items (e.g., food, infant supplies). An inability to work-whether because of transportation challenges or pregnancy-related health complications-led to unstable housing and an inability to deal with transportation challenges. Many clients mentioned that housing was a major issue, with many clients experiencing housing instability. Implications include ensuring SDOH information is collected from a trusted source who can advocate and ensure access to a wide range of local resources, ensuring policies protect pregnant women from experiencing a cascade of SDOH that may contribute to continuing health disparate infant and maternal health outcomes in African American women.

Anhydrous and Stereoretentive Fluoride-Enhanced Suzuki-Miyaura Coupling of Immunomodulatory Imide Drug Derivatives.

Immunomodulatory imide drugs form the core of many pharmaceutically relevant structures, but Csp2-Csp2 bond formation via metal-catalyzed cross coupling is difficult due to the sensitivity of the glutarimide ring ubiquitous in these structures. We report that replacement of the traditional alkali base with a fluoride source enhances a previously challenging Suzuki-Miyaura coupling on glutarimide-containing compounds with trifluoroborates. These enabling conditions are reactive enough to generate these derivatives in high yields but mild enough to preserve both the glutarimide and its sensitive stereocenter. Experimental and computational data suggest a mechanistically distinct process of π-coordination of the trifluoroborate enabled by these conditions.

The Impact of Covid-19 on Community Perinatal Doula Support Services for Black Women.

OBJECTIVES: To better understand the experiences of Black pregnant women during COVID-19, we examined Black pregnant clients' and doulas' experiences with perinatal support services amid COVID-19's social distancing protocols. METHODS: We used qualitative description, employing a social constructionist framework to interview 12 perinatal support doulas and 29 Black women who were pregnant or gave birth during the pandemic about their experiences during the pandemic, when social distancing was required. RESULTS: Three key themes were identified: (1) Clients experienced increased social isolation; (2) Doulas' exclusion from medical visits limited women's access to support and advocacy; (3) Doula support as a sisterhood helped clients mitigate effects of COVID isolation. CONCLUSIONS FOR PRACTICE: Doulas should be considered essential support persons for Black pregnant women and should not be excluded from the birthing team. Support through technology is acceptable for some clients but less desirable for others and restricted doula's ability to build rapport and be hands on with their clients.

Discovery of Non-Nucleotide Small-Molecule STING Agonists via Chemotype Hybridization.

The identification of agonists of the stimulator of interferon genes (STING) pathway has been an area of intense research due to their potential to enhance innate immune response and tumor immunogenicity in the context of immuno-oncology therapy. Initial efforts to identify STING agonists focused on the modification of 2',3'-cGAMP (1) (an endogenous STING activator ligand) and other closely related cyclic dinucleotides (CDNs). While these efforts have successfully identified novel CDNs that have progressed into the clinic, their utility is currently limited to patients with solid tumors that STING agonists can be delivered to intratumorally. Herein, we report the discovery of a unique class of non-nucleotide small-molecule STING agonists that demonstrate antitumor activity when dosed intratumorally in a syngeneic mouse model.

Ligand Enabled Pd(II)-Catalyzed γ-C(sp3)-H Lactamization of Native Amides.

γ-Lactams form important structural cores of a range of medicinally relevant natural products and clinical drugs, principal examples being the new generation of immunomodulatory imide drugs (IMiDs) and the brivaracetam family. Compared to conventional multistep synthesis, an intramolecular γ-C-H amination of aliphatic amides would allow for the direct construction of valuable γ-lactam motifs from abundant amino acid precursors. Herein we report a novel 2-pyridone ligand enabled Pd(II)-catalyzed γ-C(sp3)-H lactamization of amino acid derived native amides, providing the convenient synthesis of γ-lactams, isoindolinones, and 2-imidazolidinones. C6-Substitution of the 2-pyridone ligand is crucial for the lactam formation. This protocol features the use of N-acyl amino acids, which serve as both the directing group and cyclization partner, practical and environmentally benign tert-butyl hydrogen peroxide (TBHP) as the sole bystanding oxidant, and a broad substrate scope. The utility of this protocol was demonstrated through the two-step syntheses of a lenalidomide analog and brivaracetam from readily available carboxylic acids and amino acids.

Experiences of Black women during pregnancy: The meaning of perinatal support.

This study describes findings of a phenomenological study of Black women's experiences with a community-based perinatal support organization based in Cleveland, Ohio. Twenty-five women participated in interviews after their babies were born about how the organization in general, and perinatal support professionals (PSPs) in particular supported them during their pregnancies and the meaning of that support. The overall meaning of perinatal support was described as easing participants' transitions into motherhood through reducing uncertainty, social isolation, and stress. The three main themes described the meaning of perinatal support and included (a) easing the transition to motherhood through emotional support, expressed via love and help managing relationships; (b) easing the transition to motherhood through instrumental support, expressed via helping with basic needs and obtaining material goods for the baby; and (c) easing the transition to motherhood through informational support, expressed via help navigating systems and information, and gaining knowledge and skills around mothering and self-care. Implications for practice, policy, and research are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Conformational-Analysis-Guided Discovery of 2,3-Disubstituted Pyridine IDO1 Inhibitors.

IDO1 inhibitors have shown promise as immunotherapies for the treatment of a variety of cancers, including metastatic melanoma and renal cell carcinoma. We recently reported the identification of several novel heme-displacing IDO1 inhibitors, including the clinical molecules linrodostat (BMS-986205) and BMS-986242. Both molecules contain quinolines that, while being present in successful medicines, are known to be potentially susceptible to oxidative metabolism. Efforts to swap this quinoline with an alternative aromatic system led to the discovery of 2,3-disubstituted pyridines as suitable replacements. Further optimization, which included lowering ClogP in combination with strategic fluorine incorporation, led to the discovery of compound 29, a potent, selective IDO1 inhibitor with robust pharmacodynamic activity in a mouse xenograft model.

Discovery of Imidazopyridines as Potent Inhibitors of Indoleamine 2,3-Dioxygenase 1 for Cancer Immunotherapy.

Indoleamine 2,3-dioxygenase 1 (IDO1) has been identified as a target for small-molecule immunotherapy for the treatment of a variety of cancers including renal cell carcinoma and metastatic melanoma. This work focuses on the identification of IDO1 inhibitors containing replacements or isosteres for the amide found in BMS-986205, an amide-containing, IDO1-selective inhibitor currently in phase III clinical trials. Detailed subsequently are efforts to identify a structurally differentiated IDO1 inhibitor via the pursuit of a variety of heterocyclic isosteres, leading to the discovery of highly potent, imidazopyridine-containing IDO1 inhibitors.

Discovery and Preclinical Evaluation of BMS-986242, a Potent, Selective Inhibitor of Indoleamine-2,3-dioxygenase 1.

Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme-containing dioxygenase enzyme implicated in cancer immune response. This account details the discovery of BMS-986242, a novel IDO1 inhibitor designed for the treatment of a variety of cancers including metastatic melanoma and renal cell carcinoma. Given the substantial interest around this target for cancer immunotherapy, we sought to identify a structurally differentiated clinical candidate that performs comparably to linrodostat (BMS-986205) in terms of both in vitro potency and in vivo pharmacodynamic effect in a mouse xenograft model. On the basis of its preclinical profile, BMS-986242 was selected as a candidate for clinical development.

Catalytic α-Hydroarylation of Acrylates and Acrylamides via an Interrupted Hydrodehalogenation Reaction.

The palladium-catalyzed, α-selective hydroarylation of acrylates and acrylamides is reported. Under optimized conditions, this method is highly tolerant of a wide range of substrates including those with base sensitive functional groups and/or multiple enolizable carbonyl groups. A detailed mechanistic study was undertaken, and the high selectivity of this transformation was shown to be enabled by the formation of a [PdII(Ar)(H)] intermediate, which performs selective hydride insertion into the ß-position of α,ß-unsaturated carbonyl compounds.

"We have this awesome organization where it was built by women for women like us": Supporting African American women through their pregnancies and beyond.

Infant mortality is a problem that disproportionately affects infants of African American women, particularly residents in underserved neighborhoods. Chronic stress due to racism has been identified as an important factor in infant mortality. This study examined a novel community-based perinatal support professional (PSP) program, Birthing Beautiful Communities (BBC), in Cleveland, Ohio. BBC provides services for pregnant African American women in underserved neighborhoods with the goal of decreasing infant mortality and low birthweight rates by addressing chronic stress. Focus groups and one individual interview were conducted with the program's 14 PSPs, and 25 clients were interviewed individually. Interviews were analyzed inductively using qualitative thematic analysis to identify pervasive themes. Coders identified major themes of stress, resilience, community, cultural matching, advocacy, self-care, transformation, and self-actualization. BBC PSPs and clients alike reported the program is transforming the lives of clients by helping them address stressors. Findings suggest the community-based PSP model is an important but underused intervention in addressing infant mortality.

A unified approach to ent-atisane diterpenes and related alkaloids: synthesis of (-)-methyl atisenoate, (-)-isoatisine, and the hetidine skeleton.

A unified approach to ent-atisane diterpenes and related atisine and hetidine alkaloids has been developed from ent-kaurane (-)-steviol (1). The conversion of the ent-kaurane skeleton to the ent-atisane skeleton features a Mukaiyama peroxygenation with concomitant cleavage of the C13-C16 bond. Conversion to the atisine skeleton (9) features a C20-selective C-H activation using a Suárez modification of the Hofmann-Löffler-Freytag (HLF) reaction. A cascade sequence involving azomethine ylide isomerization followed by Mannich cyclization forms the C14-C20 bond in the hetidine skeleton (8). Finally, attempts to form the N-C6 bond of the hetisine skeleton (7) with a late-stage HLF reaction are discussed. The synthesis of these skeletons has enabled the completion of (-)-methyl atisenoate (3) and (-)-isoatisine (4).

Terpenoid-Alkaloids: Their Biosynthetic Twist of Fate and Total Synthesis.

Terpenes and alkaloids are ever-growing classes of natural products that provide new molecular structures which inspire chemists and possess a broad range of biological activity. Terpenoid-alkaloids originate from the same prenyl units that construct terpene skeletons. However, during biosynthesis, a nitrogen atom (or atoms) is introduced in the form of ß-aminoethanol, ethylamine, or methylamine. Nitrogen incorporation can occur either before, during, or after the cyclase phase. The outcome of this unique biosynthesis is the formation of natural products containing unprecedented structures. These complex structural motifs expose current limitations in organic chemistry, thus providing opportunities for invention. This review focuses on total syntheses of terpenoid-alkaloids and unique issues presented by this class of natural products. More specifically, it examines how these syntheses relate to the way terpenoid-alkaloids are made in Nature. Developments in chemistry that have facilitated these syntheses are emphasized, as well as chemical technology needed to conquer those that evade synthesis.

1-Methyl-4H-3,1-benzoxazine-2,4(1H)dione.

In its crystal structure, the title compound, C(9)H(7)NO(3), forms π-stacked dimers, with a centroid-centroid distance of 3.475 (5) Šbetween the benzenoid and the 2,4 dicarbonyl oxazine rings. These dimers then form staircase-like linear chains through further π-stacking between the benzenoid rings [centroid-centroid distance of 3.761 (2) Å]. The methyl-H atoms are disordered due to rotation about the C-N bond and were modeled with equal occupancy.

Synthesis of substituted septanosyl-1,2,3-triazoles.

A carbohydrate-based oxepine, derived from 2-deoxy-D-arabino-hexopyranose, was used to prepare a family of septanosyl-1,2,3-triazoles in four steps. DMDO mediated epoxidation of the oxepine followed by trapping of the intermediate 1,2-anhydroseptanose by sodium azide gave the beta-substituted glycosyl azide. The septanosyl azide was then reacted with a number of alkynes under thermal Huisgen or copper(I) mediated reaction conditions. Hydrogenolysis of benzyl protecting groups gave substituted septanosyl-1,2,3-triazoles. The new septanose-based structures were then evaluated as potential glycosidase inhibitors.