Here,we report a concise and divergent enantioselective total synthesis of marine sesquiterpene quinone meroterpenoids(+)-dysidavarones A–C(1–3)using predysidavarone 6 as a key common intermediate.The highly straine...Here,we report a concise and divergent enantioselective total synthesis of marine sesquiterpene quinone meroterpenoids(+)-dysidavarones A–C(1–3)using predysidavarone 6 as a key common intermediate.The highly strained and bridged eight-membered carbocycle of predysidavarone 6 was constructed by a one-pot intermolecular alkylation and intramolecular arylation of Wieland–Miescher ketone derivative 11 and benzyl bromide 12.The total synthesis of(+)-dysidavarones A–C(1–3)was achieved from predysidavarone 6 in a divergent manner by a late-stage introduction of the ethoxy group,which reveals the possible source of the ethoxy group within(+)-dysidavarones A–C(1–3)and provides a late-stage modifiable route for the synthesis of dysidavarone analogs for further anti-cancer activity evaluation.展开更多
Face mask use by the general public for limiting the spread of the COVID-19 pandemic is controversial,though increasingly recommended,and the potential of this intervention is not well understood.We develop a compartm...Face mask use by the general public for limiting the spread of the COVID-19 pandemic is controversial,though increasingly recommended,and the potential of this intervention is not well understood.We develop a compartmental model for assessing the communitywide impact of mask use by the general,asymptomatic public,a portion of which may be asymptomatically infectious.Model simulations,using data relevant to COVID-19 dynamics in the US states of New York and Washington,suggest that broad adoption of even relatively ineffective face masks may meaningfully reduce community transmission of COVID-19 and decrease peak hospitalizations and deaths.Moreover,mask use decreases the effective transmission rate in nearly linear proportion to the product of mask effectiveness(as a fraction of potentially infectious contacts blocked)and coverage rate(as a fraction of the general population),while the impact on epidemiologic outcomes(death,hospitalizations)is highly nonlinear,indicating masks could synergize with other nonpharmaceutical measures.Notably,masks are found to be useful with respect to both preventing illness in healthy persons and preventing asymptomatic transmission.Hypothetical mask adoption scenarios,for Washington and New York state,suggest that immediate near universal(80%)adoption of moderately(50%)effective masks could prevent on the order of 17e45%of projected deaths over two months in New York,while decreasing the peak daily death rate by 34e58%,absent other changes in epidemic dynamics.Even very weak masks(20%effective)can still be useful if the underlying transmission rate is relatively low or decreasing:InWashington,where baseline transmission is much less intense,80%adoption of such masks could reduce mortality by 24e65%(and peak deaths 15e69%),compared to 2e9%mortality reduction in New York(peak death reduction 9e18%).Our results suggest use of face masks by the general public is potentially of high value in curtailing community transmission and the burden of the pandemic.The community-wide benefits are likely to be greatest when face masks are used in conjunction with other non-pharmaceutical practices(such as social-distancing),and when adoption is nearly universal(nation-wide)and compliance is high.展开更多
基金financially supported by the National Natural Science Foundation of China(Nos.22171146,21971121,and 22188101 to ZL)the China Postdoctoral Science Foundation(No.2021M701775 to CC)。
文摘Here,we report a concise and divergent enantioselective total synthesis of marine sesquiterpene quinone meroterpenoids(+)-dysidavarones A–C(1–3)using predysidavarone 6 as a key common intermediate.The highly strained and bridged eight-membered carbocycle of predysidavarone 6 was constructed by a one-pot intermolecular alkylation and intramolecular arylation of Wieland–Miescher ketone derivative 11 and benzyl bromide 12.The total synthesis of(+)-dysidavarones A–C(1–3)was achieved from predysidavarone 6 in a divergent manner by a late-stage introduction of the ethoxy group,which reveals the possible source of the ethoxy group within(+)-dysidavarones A–C(1–3)and provides a late-stage modifiable route for the synthesis of dysidavarone analogs for further anti-cancer activity evaluation.
基金One of the authors(ABG)acknowledge the support,in part,of the Simons Foundation(Award#585022)the National Science Foundation(Award 1917512).
文摘Face mask use by the general public for limiting the spread of the COVID-19 pandemic is controversial,though increasingly recommended,and the potential of this intervention is not well understood.We develop a compartmental model for assessing the communitywide impact of mask use by the general,asymptomatic public,a portion of which may be asymptomatically infectious.Model simulations,using data relevant to COVID-19 dynamics in the US states of New York and Washington,suggest that broad adoption of even relatively ineffective face masks may meaningfully reduce community transmission of COVID-19 and decrease peak hospitalizations and deaths.Moreover,mask use decreases the effective transmission rate in nearly linear proportion to the product of mask effectiveness(as a fraction of potentially infectious contacts blocked)and coverage rate(as a fraction of the general population),while the impact on epidemiologic outcomes(death,hospitalizations)is highly nonlinear,indicating masks could synergize with other nonpharmaceutical measures.Notably,masks are found to be useful with respect to both preventing illness in healthy persons and preventing asymptomatic transmission.Hypothetical mask adoption scenarios,for Washington and New York state,suggest that immediate near universal(80%)adoption of moderately(50%)effective masks could prevent on the order of 17e45%of projected deaths over two months in New York,while decreasing the peak daily death rate by 34e58%,absent other changes in epidemic dynamics.Even very weak masks(20%effective)can still be useful if the underlying transmission rate is relatively low or decreasing:InWashington,where baseline transmission is much less intense,80%adoption of such masks could reduce mortality by 24e65%(and peak deaths 15e69%),compared to 2e9%mortality reduction in New York(peak death reduction 9e18%).Our results suggest use of face masks by the general public is potentially of high value in curtailing community transmission and the burden of the pandemic.The community-wide benefits are likely to be greatest when face masks are used in conjunction with other non-pharmaceutical practices(such as social-distancing),and when adoption is nearly universal(nation-wide)and compliance is high.
基金This research is supported by the National Natural Science Foundations of China under Grant No. 60674059, the 11th 5-Year Plan Key Research Project of China under Grant No. 2004BA721A03, the China National Key Special Project for the Preventions and Cures of Important Infectious Diseases under Grant No. 2008ZX10005- 006.
