Total Synthesis of (−)-Nakadomarin A

The convergent synthesis of the polycyclic alkaloid (−)-nakadomarin A (<b>1</b>) is reported. The synthesis plan identified macrocyclic lactam <b>4</b> as one of the important synthons (eight steps). The other synthon (five steps) was bicyclo[6.3.0] lactam <b>5</b> containing a single stereocenter that controlled all of the subsequent stereochemistry during the assembly process. A silyl triflate-promoted cascade of <b>4</b> and <b>5</b> was used to assemble the bulk of the alkaloid skeleton with the exception of the C5–C6 bond. The nakadomarin synthesis was then completed in one additional step

Total Synthesis of (−)-Nakadomarin A

The convergent synthesis of the polycyclic alkaloid (−)-nakadomarin A (<b>1</b>) is reported. The synthesis plan identified macrocyclic lactam <b>4</b> as one of the important synthons (eight steps). The other synthon (five steps) was bicyclo[6.3.0] lactam <b>5</b> containing a single stereocenter that controlled all of the subsequent stereochemistry during the assembly process. A silyl triflate-promoted cascade of <b>4</b> and <b>5</b> was used to assemble the bulk of the alkaloid skeleton with the exception of the C5–C6 bond. The nakadomarin synthesis was then completed in one additional step

Total Synthesis of (−)-Nakadomarin A

The convergent synthesis of the polycyclic alkaloid (−)-nakadomarin A (<b>1</b>) is reported. The synthesis plan identified macrocyclic lactam <b>4</b> as one of the important synthons (eight steps). The other synthon (five steps) was bicyclo[6.3.0] lactam <b>5</b> containing a single stereocenter that controlled all of the subsequent stereochemistry during the assembly process. A silyl triflate-promoted cascade of <b>4</b> and <b>5</b> was used to assemble the bulk of the alkaloid skeleton with the exception of the C5–C6 bond. The nakadomarin synthesis was then completed in one additional step

Total Synthesis of (−)-Nakadomarin A

The convergent synthesis of the polycyclic alkaloid (−)-nakadomarin A (<b>1</b>) is reported. The synthesis plan identified macrocyclic lactam <b>4</b> as one of the important synthons (eight steps). The other synthon (five steps) was bicyclo[6.3.0] lactam <b>5</b> containing a single stereocenter that controlled all of the subsequent stereochemistry during the assembly process. A silyl triflate-promoted cascade of <b>4</b> and <b>5</b> was used to assemble the bulk of the alkaloid skeleton with the exception of the C5–C6 bond. The nakadomarin synthesis was then completed in one additional step

Global Transplantation COVID Report March 2020

The COVID-19 pandemic has hit the entire world in an almost unprecedented way. The crisis has spread rapidly, disease burden and casualties continue to rise, and the impact of the crisis is spreading through developing countries. Social distancing, travel restrictions, and intensified testing have improved the rate of the rise in new cases in some regions; however, it remains unclear when normality will return. Mechanisms of the disease remain largely unclear; treatment, if available, is mostly supportive. As during times of war, the challenges of the coronavirus crisis change our views in almost any aspect.</p

A multi-center retrospective cohort study defines the spectrum of kidney pathology in Coronavirus 2019 Disease (COVID-19)

Kidney failure is common in patients with Coronavirus Disease-19 (COVID-19), resulting in increased morbidity and mortality. In an international collaboration, 284 kidney biopsies were evaluated to improve understanding of kidney disease in COVID-19. Diagnoses were compared to five years of 63,575 native biopsies prior to the pandemic and 13,955 allograft biopsies to identify diseases that have increased in patients with COVID-19. Genotyping for APOL1 G1 and G2 alleles was performed in 107 African American and Hispanic patients. Immunohistochemistry for SARS-CoV-2 was utilized to assess direct viral infection in 273 cases along with clinical information at the time of biopsy. The leading indication for native biopsy was acute kidney injury (45.4%), followed by proteinuria with or without concurrent acute kidney injury (42.6%). There were more African American patients (44.6%) than patients of other ethnicities. The most common diagnosis in native biopsies was collapsing glomerulopathy (25.8%), which was associated with high-risk APOL1 genotypes in 91.7% of cases. Compared to the five-year biopsy database, the frequency of myoglobin cast nephropathy and proliferative glomerulonephritis with monoclonal IgG deposits was also increased in patients with COVID-19 (3.3% and 1.7%, respectively), while there was a reduced frequency of chronic conditions (including diabetes mellitus, IgA nephropathy, and arterionephrosclerosis) as the primary diagnosis. In transplants, the leading indication was acute kidney injury (86.4%), for which rejection was the predominant diagnosis (61.4%). Direct SARS-CoV-2 viral infection was not identified. Thus, our multi-center large case series identified kidney diseases that disproportionately affect patients with COVID-19 and demonstrated a high frequency of APOL1 high-risk genotypes within this group, with no evidence of direct viral infection within the kidney

A multi-center retrospective cohort study defines the spectrum of kidney pathology in Coronavirus 2019 Disease (COVID-19).

Kidney failure is common in patients with Coronavirus Disease-19 (COVID-19), resulting in increased morbidity and mortality. In an international collaboration, 284&nbsp;kidney biopsies were evaluated to improve understanding of kidney disease in COVID-19. Diagnoses were compared to five years of 63,575 native biopsies prior to the pandemic and 13,955 allograft biopsies to identify diseases that have increased in patients with COVID-19. Genotyping for APOL1 G1 and&nbsp;G2 alleles was performed in 107 African American and Hispanic patients. Immunohistochemistry for SARS-CoV-2 was utilized to assess direct viral infection in 273 cases along with clinical information at the time of biopsy. The leading indication for native biopsy was acute kidney injury (45.4%), followed by proteinuria with or without concurrent acute kidney injury (42.6%). There were more African American patients (44.6%) than patients of other ethnicities. The most common diagnosis in native biopsies was collapsing glomerulopathy (25.8%), which was associated with high-risk APOL1 genotypes in 91.7% of cases. Compared to the five-year biopsy database, the frequency of myoglobin cast nephropathy and proliferative glomerulonephritis with monoclonal IgG deposits was also increased in patients with COVID-19 (3.3% and 1.7%, respectively), while there was a reduced frequency of chronic conditions (including diabetes mellitus, IgA nephropathy, and arterionephrosclerosis) as the primary diagnosis. In transplants, the leading indication was acute kidney injury (86.4%), for which rejection was the predominant diagnosis (61.4%). Direct SARS-CoV-2 viral infection was not identified. Thus, our multi-center large case series identified kidney diseases that disproportionately affect patients with COVID-19 and demonstrated a high frequency of APOL1 high-risk genotypes within this group, with no evidence of direct viral infection within the&nbsp;kidney