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Background: With what has been known as the "triple-win effect", introducing information and communication technologies (ICTs) in the health care of neurodegenerative diseases is beneficial in delaying the need for institutional care, reducing the associated health care costs, reducing the caregiving burden, and improving individuals' quality of life. Nevertheless, the mismatch between the users' expectations and their actual needs remains one of the main challenges that can reduce the usability of technology solutions. Therefore, the European project Personalized Integrated Care Promoting Quality of Life for Older People (PROCare4Life), which aimed to develop an ICT-based platform for all parties involved in the health care of neurodegenerative diseases, adopted a user-centered design approach, where all users are involved from the inception and throughout the platform development and implementation to integrate their needs and requirements in the proposed platform., Objective: This paper presents the results of a study on the needs and requirements of the potential end users (older people with neurodegenerative diseases, caregivers, and health care professionals) and other key stakeholders in the development of the PROCare4Life platform., Methods: A mixed qualitative and quantitative study design was used, including 2 web-based surveys, 40 interviews, and 4 workshops. The study was conducted between April and September 2020 in 5 European countries: Germany, Italy, Portugal, Romania, and Spain. Both data types were analyzed separately and then merged and interpreted, with greater priority placed on qualitative research., Results: A total of 217 participants were recruited; 157 (72.4%) of them completed the web-based surveys (n=85, 54.1% patients and n=72, 45.9% caregivers), and 60 (27.6%) individuals participated in the qualitative research (20/60, 33% health care professionals; 5/60, 8% patients; 5/60, 8% caregivers; and 30/60, 50% key stakeholders). We identified 3 main themes (T): (T1) experiences associated with illness, (T2) thoughts about the platform technology, and (T3) desired properties. Alerts for adverse events, communication tools, reminders, and monitoring are constantly needed functionalities, whereas ease of use, personalization, and user-friendliness are foreseen as necessary features., Conclusions: This paper identified the key personal, social, and health factors that influence the daily lives of the potential end users and reflected on their needs and expectations regarding the design of the proposed PROCare4Life platform. The collected data were useful for the development of the PROCare4Life platform. Although the combination and collection of features for diverse user groups are typical for integrated care platforms, it results in exponential complexity for designers, developers, and users. Contradicting opinions and several concerns in this study demonstrate that an ICT-integrated care platform should not promise too much for too many. Instead, selection, focus, and, sometimes, restriction to essentials are necessary. Users and other stakeholders should be involved in these decisions., International Registered Report Identifier (irrid): RR2-10.2196/22463., (©Mona Ahmed, Mayca Marín, Daniella How, Elda Judica, Peppino Tropea, Ellen Bentlage, Joaquim J Ferreira, Raquel Bouça-Machado, Michael Brach. Originally published in JMIR Formative Research (https://formative.jmir.org), 30.11.2022.)

Freezing of gait can cause reduced independence and quality of life for many with Parkinson's disease. Episodes frequently occur at points of transition such as navigating a doorway. Therapeutic interventions, i.e., drugs and exercise, do not always successfully mitigate episodes. There are several different, but not exclusive causes for freezing of gait. People with freezing of gait are able to navigate dynamic situations like stairways by utilizing a different attentional strategy to over-ground walking, but may freeze when passing through a doorway. The question is, is it possible to employ a special attentional strategy to prevent freezing at this point? Motor imagery allows for learning motor skills in absolute safety and has been widely employed in a variety of populations, including other neuro-compromised groups. Motor imagery is not studied in a homologous manner in people with Parkinson's Disease, leading to conflicting results, but may have the potential to establish a different attentional strategy which allows a subject to mitigate freezing of gait episodes. This paper will identify and discuss the questions that still need to be answered in order to consider this approach i.e., can this population access motor imagery, can motor imagery alter the attentional strategy employed when moving through doorways, what is the best motor imagery approach for people with Parkinson's Disease and freezing of gait, and what dosage is most effective, while briefly outlining future research considerations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 How, Wagner and Brach.)

Importance: People with bilateral vestibulopathy experience severe balance and mobility issues. Fear and anxiety are associated with reduced activity, which can further affect balance and fall risk. Understanding and intervening on falls in this population is essential. The aims of this narrative review are to provide an overview of the current knowledge and applied methods on fall incidence, causes, and injuries in bilateral vestibulopathy., Observations: Eleven articles reporting falls incidence in people with bilateral vestibulopathy were deemed eligible, including 3 prospective and 8 retrospective studies, with a total of 359 participants, of whom 149 (42%) fell during the assessed period. When reported, the most common perceived causes of falls were loss of balance, darkness, and uneven ground. Information on sustained injuries was limited, with bruises and scrapes being the most common, and only 4 fractures were reported. As most studies included falls as a secondary, descriptive outcome measure, fall data obtained using best practice guidelines were lacking. Only 6 studies reported their definition of a fall, of which 2 studies explicitly reported the way participants were asked about their fall status. Only 3 studies performed a prospective daily fall assessment using monthly fall diaries (a recommended practice), whereas the remaining studies retrospectively collected fall-related data through questionnaires or interviews. While most studies reported the number of people who did and did not fall, the number of total falls in individual studies was lacking., Conclusions and Relevance: The findings from this review suggest that falls in people with bilateral vestibulopathy are common but remain an understudied consequence of the disease. Larger prospective studies that follow best practice guidelines for fall data collection with the aim of obtaining and reporting fall data are required to improve current fall risk assessments and interventions in bilateral vestibulopathy.

Symptoms of psychological distress and disorder have been widely reported in people under quarantine during the COVID-19 pandemic; in addition to severe disruption of peoples' daily activity and sleep patterns. This study investigates the association between physical-activity levels and sleep patterns in quarantined individuals. An international Google online survey was launched in April 6 th , 2020 for 12-weeks. Forty-one research organizations from Europe, North-Africa, Western-Asia, and the Americas promoted the survey through their networks to the general society, which was made available in 14 languages. The survey was presented in a differential format with questions related to responses "before" and "during" the confinement period. Participants responded to the Pittsburgh Sleep Quality Index (PSQI) questionnaire and the short form of the International Physical Activity Questionnaire. 5056 replies (59.4% female), from Europe (46.4%), Western-Asia (25.4%), America (14.8%) and North-Africa (13.3%) were analysed. The COVID-19 home confinement led to impaired sleep quality, as evidenced by the increase in the global PSQI score (4.37 ± 2.71 before home confinement vs. 5.32 ± 3.23 during home confinement) (p < 0.001). The frequency of individuals experiencing a good sleep decreased from 61% (n = 3063) before home confinement to 48% (n = 2405) during home confinement with highly active individuals experienced better sleep quality (p < 0.001) in both conditions. Time spent engaged in all physical-activity and the metabolic equivalent of task in each physical-activity category (i.e., vigorous, moderate, walking) decreased significantly during COVID-19 home confinement (p < 0.001). The number of hours of daily-sitting increased by ~2 hours/days during home confinement (p < 0.001). COVID-19 home confinement resulted in significantly negative alterations in sleep patterns and physical-activity levels. To maintain health during home confinement, physical-activity promotion and sleep hygiene education and support are strongly warranted., Competing Interests: All authors declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work., (Copyright © Biology of Sport 2021.)

Background: The COVID-19 lockdown could engender disruption to lifestyle behaviors, thus impairing mental wellbeing in the general population. This study investigated whether sociodemographic variables, changes in physical activity, and sleep quality from pre- to during lockdown were predictors of change in mental wellbeing in quarantined older adults., Methods: A 12-week international online survey was launched in 14 languages on 6 April 2020. Forty-one research institutions from Europe, Western-Asia, North-Africa, and the Americas, promoted the survey. The survey was presented in a differential format with questions related to responses "pre" and "during" the lockdown period. Participants responded to the Short Warwick-Edinburgh Mental Wellbeing Scale, the Pittsburgh Sleep Quality Index (PSQI) questionnaire, and the short form of the International Physical Activity Questionnaire., Results: Replies from older adults (aged >55 years, n = 517), mainly from Europe (50.1%), Western-Asia (6.8%), America (30%), and North-Africa (9.3%) were analyzed. The COVID-19 lockdown led to significantly decreased mental wellbeing, sleep quality, and total physical activity energy expenditure levels (all p < 0.001). Regression analysis showed that the change in total PSQI score and total physical activity energy expenditure (F (2, 514) = 66.41 p < 0.001) were significant predictors of the decrease in mental wellbeing from pre- to during lockdown ( p < 0.001, R 2 : 0.20)., Conclusion: COVID-19 lockdown deleteriously affected physical activity and sleep patterns. Furthermore, change in the total PSQI score and total physical activity energy expenditure were significant predictors for the decrease in mental wellbeing.

Although recognised as effective measures to curb the spread of the COVID-19 outbreak, social distancing and self-isolation have been suggested to generate a burden throughout the population. To provide scientific data to help identify risk factors for the psychosocial strain during the COVID-19 outbreak, an international cross-disciplinary online survey was circulated in April 2020. This report outlines the mental, emotional and behavioural consequences of COVID-19 home confinement. The ECLB-COVID19 electronic survey was designed by a steering group of multidisciplinary scientists, following a structured review of the literature. The survey was uploaded and shared on the Google online survey platform and was promoted by thirty-five research organizations from Europe, North Africa, Western Asia and the Americas. Questions were presented in a differential format with questions related to responses "before" and "during" the confinement period. 1047 replies (54% women) from Western Asia (36%), North Africa (40%), Europe (21%) and other continents (3%) were analysed. The COVID-19 home confinement evoked a negative effect on mental wellbeing and emotional status (P < 0.001; 0.43 ≤ d ≤ 0.65) with a greater proportion of individuals experiencing psychosocial and emotional disorders (+10% to +16.5%). These psychosocial tolls were associated with unhealthy lifestyle behaviours with a greater proportion of individuals experiencing (i) physical (+15.2%) and social (+71.2%) inactivity, (ii) poor sleep quality (+12.8%), (iii) unhealthy diet behaviours (+10%), and (iv) unemployment (6%). Conversely, participants demonstrated a greater use (+15%) of technology during the confinement period. These findings elucidate the risk of psychosocial strain during the COVID-19 home confinement period and provide a clear remit for the urgent implementation of technology-based intervention to foster an Active and Healthy Confinement Lifestyle AHCL)., Competing Interests: All authors declare no competing interest., (Copyright © 2020 Termedia.)

Background: Dementias-including Alzheimer disease-and Parkinson disease profoundly impact the quality of life of older population members and their families. PROCare4Life (Personalized Integrated Care Promoting Quality of Life for Older Adults) is a European project that recognizes the benefit of technology-based integrated care models in improving the care coordination and the quality of life of these target groups. This project proposes an integrated, scalable, and interactive care platform targeting older people suffering from neurodegenerative diseases, their caregivers, and socio-health professionals. PROCare4Life adopts a user-centered design approach from the early stage and throughout platform development and implementation, during which the platform is designed and adapted to the needs and requirements of all the involved users., Objective: This paper presents the study protocol for investigating users' needs and requirements regarding the design of the proposed PROCare4Life platform., Methods: A mixed qualitative and quantitative study design is utilized, including online surveys, interviews, and workshops. The study aimed to recruit approximately 200 participants, including patients diagnosed with dementia or Parkinson disease, caregivers, socio-health professionals, and other stakeholders, from five different European countries: Germany, Italy, Portugal, Romania, and Spain., Results: The study took place between April and September 2020. Recruitment is now closed, and all the data have been collected and analyzed in order to be used in shaping the large-scale pilot phase of the PROCare4Life project. Results of the study are expected to be published in spring 2021., Conclusions: This paper charts the protocol for a user-centered design approach at the early stage of the PROCare4Life project in order to shape and influence an integrated health platform suitable for its intended target group and purpose., International Registered Report Identifier (irrid): DERR1-10.2196/22463., (©Mona Ahmed, Mayca Marín, Raquel Bouça-Machado, Daniella How, Elda Judica, Peppino Tropea, Ellen Bentlage, Michael Brach. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 12.01.2021.)

Background: Public health recommendations and government measures during the COVID-19 pandemic have enforced restrictions on daily-living. While these measures are imperative to abate the spreading of COVID-19, the impact of these restrictions on mental health and emotional wellbeing is undefined. Therefore, an international online survey (ECLB-COVID19) was launched on April 6, 2020 in seven languages to elucidate the impact of COVID-19 restrictions on mental health and emotional wellbeing., Methods: The ECLB-COVID19 electronic survey was designed by a steering group of multidisciplinary scientists, following a structured review of the literature. The survey was uploaded and shared on the Google online-survey-platform and was promoted by thirty-five research organizations from Europe, North-Africa, Western-Asia and the Americas. All participants were asked for their mental wellbeing (SWEMWS) and depressive symptoms (SMFQ) with regard to "during" and "before" home confinement., Results: Analysis was conducted on the first 1047 replies (54% women) from Asia (36%), Africa (40%), Europe (21%) and other (3%). The COVID-19 home confinement had a negative effect on both mental-wellbeing and on mood and feelings. Specifically, a significant decrease (p < .001 and Δ% = 9.4%) in total score of the SWEMWS questionnaire was noted. More individuals (+12.89%) reported a low mental wellbeing "during" compared to "before" home confinement. Furthermore, results from the mood and feelings questionnaire showed a significant increase by 44.9% (p < .001) in SMFQ total score with more people (+10%) showing depressive symptoms "during" compared to "before" home confinement., Conclusion: The ECLB-COVID19 survey revealed an increased psychosocial strain triggered by the home confinement. To mitigate this high risk of mental disorders and to foster an Active and Healthy Confinement Lifestyle (AHCL), a crisis-oriented interdisciplinary intervention is urgently needed., Competing Interests: All authors have completed the Unified Competing Interest form (available on request from the corresponding author). Authors except Laura Riemann declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work. Laura Riemann declare to have a commercial affiliation “PharmIAD, Inc, Savannah, GA, USA”. This funder provided support in the form of salaries for Laurel Riemann, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of this author are articulated in the ‘author contributions’ section. This commercial affiliation does not alter our adherence to PLOS ONE policies on sharing data and materials.

Clinical Data: We hereby report a case of limb salvage involving a 64-year-old man who was hospitalized with ischemic foot ulcers for two months. Endarterectomy with patching and stenting of the left iliofemoral artery failed. A composite bypass of two segments of the endarterectomized superficial femoral artery and a cryopreserved saphenous vein graft was implanted one week later. On day 4 postoperatively, an infection (Staphylococcus epidermidis and Pseudomonas aeruginosa) was treated empirically with antibiotics. Four months later, the femoro-tibial bypass thrombosed and the patency was restored by thrombolysis. The aneurysmal cryopreserved vein was excised. Iterative complications followed and final success was attained after implantation of autologous cephalic and basilic veins. Four years later, this femoro-tibial is still patent., Pathological Analyses: After a gross observation, the explant was dissected and the most significant sections were processed for histology, followed by analyses in scanning electron microscopy, light microscopy and transmission electron microscopy., Results: The explanted specimen showed a smooth flow surface proximally but a severe distortion distally, with an accumulation of poorly organized mural thrombi. The wall of the arterialized vein was accompanied with an important inflammatory reaction. The degradation of the collagen structure was evidenced in TEM. The fibrils of collagen were still individualized but were fragmented and did not display parallelly. The regular banding was preserved. The presence of Pseudomonas aeruginosa was shown inside the wall of the homologous vein., Comments: In case of sepsis, the most aggressive antibiotic treatments cannot fully eliminate the bacteremic colonizations within the wall of an alternative conduit. The cephalic and basilic autologous veins are proved to be preferable in absence of the autologous saphenous vein. The amputation was prevented and four years later the bypass is still patent. This is an outstanding result based upon the comorbidities of the patient. The most aggressive harvesting shall be recommended. This patient represented a considerable challenge and the clinical result is highly gratifying: the search for the autologous cephalic and basilic veins proved to be worth the effort., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Diminished volumes of habitual physical activity and increased sedentary levels have been observed as a result of COVID-19 home-confinement. Consequences of inactivity, including a higher mortality rate and poorer general health and fitness, have been reported. This systematic review aimed to provide practical recommendations for maintaining active lifestyles during pandemics. In May 2020, two electronic databases (PubMed; Web of Science) were used to search for relevant studies. A total of 1206 records were screened by two researchers. Thirty-one relevant studies were included in this systematic review, in which the methodological quality was assessed. With regard to six studies, which explicitly dealt with physical activity during COVID-19, the evidence level is classified by three articles to level II, and in the other three to level VI. Regarding the physical activity recommendations in these papers, three of them were classified to a medium, and the same number to a weak evidence base. Of the 25 papers which refer to other pandemics and/or isolation situations, one was classified to evidence level I, four were ranged to level II, three to level III, one to level V, and the others to level VI. This systematic review revealed that reduced physical activity levels are of serious concern during home confinement in pandemic times. The recommendations provided by many international organizations to maintain active lifestyles during these times mainly target the general population, with less consideration for vulnerable populations (e.g., older adults, people with health issues). Therefore, personalized and supervised physical activity programs are urgently needed, with the option to group-play physical activity programs (e.g., exergames). These can be assisted, delivered, and disseminated worldwide through information and communication technology solutions. If it is permitted and safe, being active outside in daylight is advised, with an effort level of mild to moderate using the rating of perceived exertion scale. Relaxation techniques should be integrated into the daily routine to reduce stress levels. On the evidence base and levels of the included articles in this review, the results need to be interpreted with caution. Given that policies are different across regions and countries, further research is needed to categorize recommendations according to different social-distancing scenarios.

Public health recommendations and governmental measures during the new coronavirus disease (COVID-19) pandemic have enforced numerous restrictions on daily living including social distancing, isolation, and home confinement. While these measures are imperative to mitigate spreading of COVID-19, the impact of these restrictions on psychosocial health is undefined. Therefore, an international online survey was launched in April 2020 to elucidate the behavioral and lifestyle consequences of COVID-19 restrictions. This report presents the preliminary results from more than one thousand responders on social participation and life satisfaction., Methods: Thirty-five research organizations from Europe, North-Africa, Western Asia, and the Americas promoted the survey through their networks to the general society, in 7 languages (English, German, French, Arabic, Spanish, Portuguese, and Slovenian). Questions were presented in a differential format with questions related to responses "before" and "during" confinement conditions., Results: 1047 participations (54% women) from Asia (36%), Africa (40%), Europe (21%), and others (3%) were included in the analysis. Findings revealed psychosocial strain during the enforced COVID-19 home confinement. Large decreases ( p < 0.001) in the amount of social activity through family (-58%), friends/neighbors (-44.9%), or entertainment (-46.7%) were triggered by the enforced confinement. These negative effects on social participation were also associated with lower life satisfaction (-30.5%) during the confinement period. Conversely, the social contact score through digital technologies significantly increased ( p < 0.001) during the confinement period with more individuals (+24.8%) being socially connected through digital technology., Conclusion: These preliminary findings elucidate the risk of psychosocial strain during the early COVID-19 home confinement period in 2020. Therefore, in order to mitigate the negative psychosocial effects of home confinement, implementation of national strategies focused on promoting social inclusion through a technology-based solution is strongly suggested.

Background: Public health recommendations and governmental measures during the COVID-19 pandemic have resulted in numerous restrictions on daily living including social distancing, isolation and home confinement. While these measures are imperative to abate the spreading of COVID-19, the impact of these restrictions on health behaviours and lifestyles at home is undefined. Therefore, an international online survey was launched in April 2020, in seven languages, to elucidate the behavioural and lifestyle consequences of COVID-19 restrictions. This report presents the results from the first thousand responders on physical activity (PA) and nutrition behaviours., Methods: Following a structured review of the literature, the "Effects of home Confinement on multiple Lifestyle Behaviours during the COVID-19 outbreak (ECLB-COVID19)" Electronic survey was designed by a steering group of multidisciplinary scientists and academics. The survey was uploaded and shared on the Google online survey platform. Thirty-five research organisations from Europe, North-Africa, Western Asia and the Americas promoted the survey in English, German, French, Arabic, Spanish, Portuguese and Slovenian languages. Questions were presented in a differential format, with questions related to responses "before" and "during" confinement conditions., Results: 1047 replies (54% women) from Asia (36%), Africa (40%), Europe (21%) and other (3%) were included in the analysis. The COVID-19 home confinement had a negative effect on all PA intensity levels (vigorous, moderate, walking and overall). Additionally, daily sitting time increased from 5 to 8 h per day. Food consumption and meal patterns (the type of food, eating out of control, snacks between meals, number of main meals) were more unhealthy during confinement, with only alcohol binge drinking decreasing significantly., Conclusion: While isolation is a necessary measure to protect public health, results indicate that it alters physical activity and eating behaviours in a health compromising direction. A more detailed analysis of survey data will allow for a segregation of these responses in different age groups, countries and other subgroups, which will help develop interventions to mitigate the negative lifestyle behaviours that have manifested during the COVID-19 confinement., Competing Interests: The authors report no conflicts of interest

Transcatheter aortic valve implantation (TAVI) has gained considerable acceptance in the past decade due to its lower risks than conventional open-heart surgery. However, the deformation and delamination of the leaflets during the crimping procedure have raised questions about the durability and long-term serviceability of the pericardium tissue from which the leaflets are made. The collagen architecture, wall thickness and mechanical properties of donkey pericardium were investigated to assess its suitability as an alternative material for the manufacture of heart valves. Coupons sampled from different locations of donkey pericardium were investigated. Bovine, equine, and porcine pericardium specimens served as controls. The donkey pericardium had a similar surface morphology to that of the control pericardia except for the wavy topology on both the fibrous and serous sides. The average thickness of donkey pericardium (ca. 120 µm) was significantly lower than that from bovine (375 µm) and equine (410 µm), but slightly higher than that from porcine (99 µm) specimens. The interlaced wavy collagen bundles in the pericardium were composed of collagen fibers about 100 nm in diameter. This unique structure ensures that the donkey pericardium has a comparable ultimate tensile strength (UTS) and a much higher failure strain than the commercial pericardia used for the manufacture of heart valves. The donkey pericardium has an organized wavy collagen bundle architecture similar to that of bovine pericardium and has a satisfactory UTS and high failure strain. The thin and strong donkey pericardium might be a good candidate valve leaflet material for TAVI., (© 2019 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

The prevention of aggrecan (a key component of cartilage) cleavage via the inhibition of aggrecanase-1 may provide a unique opportunity to stop the progression of cartilage degradation in osteoarthritis. The evaluation of a series of biphenylsulfonamides resulted in the identification of the ((4-keto)-phenoxy)methyl biphenyl-4-sulfonamides analogs (19-21 and 24) with improved Agg-1 inhibition and MMP-2, MMP-13 activity.

Deprotection of p-nitrobenzyl esters and valyl carbamates in carbapenem CL 192,276 produced the active compound OCA-983 in excellent yields. Straight chain alkanols such as 1-butanol, 1-pentanol and 1-hexanol in water at certain ratios were effective solvent systems. Alkyl acetates in water also resulted in simultaneous deprotection of PNB and PNZ side-chains albeit at slower rates. The deprotected carbapenem was isolated in excellent yield and purity after removal of the aqueous media. This procedure is applicable to sensitive compounds that are soluble in water without the need to use a buffer and allows for ease of isolation from the aqueous phase.

The effect of introducing hydrophobic groups onto the disaccharide portion of the mannopeptimycins has been examined. Under acid-catalyzed conditions dimethyl acetals and ketals react on the terminal mannose of the disaccharide moiety of mannopeptimycin-alpha and the cyclohexylalanyl analogue 2. The preferentially formed monofunctionalized 4,6-acetals and -ketals display potent antibacterial activities against Gram-positive microorganisms, including MRSA, PRSP, and VRE pathogens.

A number of 6-O-ether and 4-O-ether derivatives of mannopeptimycin-alpha with different steric bulk and lipophilicity were synthesized for structure-activity relationship study. Novel iodo and bromo mannopeptimycin-alpha were also prepared. These compounds were synthesized via electrophilic aromatic substitution. Many of the new ether derivatives exhibited potent antibacterial activity against Gram-positive resistant strains including VRE, MRSA, and PRSP.

A series of benzoxazole derivatives of the mannopeptimycin glycopeptide antibiotics was synthesized via a novel benzoxazole formation reaction by treating aminophenol of mannopeptimycin-beta with an aldehyde and DDQ in DMF. Some of these derivatives (e.g., 5b, 5d, 5m, and 7b) showed good activity against Gram-(+) bacteria when compared to the parent compound mannopeptimycin-beta.

Novel ether derivatives of mannopeptimycin glycopeptide were synthesized to probe their SAR. Many of these derivatives exhibited potent antibacterial activity against methicillin resistant and vancomycin resistant strains. These ether derivatives were prepared via reductive ring cleavage of acetals to give a mixture of 6-O, 4-O, 3-O, and 2-O-ether isomers. Both 6-O-ether and 4-O-ether showed significantly enhanced antibacterial activity over the parent and the isovalerate esters.