RESUMO
The first total synthesis of daphgraciline has been achieved, which also represents the first example of the synthesis of Daphniphyllum yuzurine-type alkaloids (â¼50 members). The unique bridged azabicyclo[4.3.1] ring system in the yuzurine-type subfamily was efficiently and diastereoselectively assembled via a mild type II [5+2] cycloaddition for the first time. The compact tetracyclic [6-7-5-5] skeleton was installed efficiently via an intramolecular Diels-Alder reaction, followed by a benzilic acid-type rearrangement. The synthetically challenging spiro tetrahydropyran moiety in the final product was installed diastereoselectively via a TiIII-mediated reductive epoxide coupling reaction. Potential access to enantioenriched daphgraciline is presented.
Assuntos
Alcaloides , Estrutura Molecular , Reação de Cicloadição , Compostos de Epóxi , EstereoisomerismoRESUMO
The first and catalytic enantioselective total synthesis of hypocrolide A (>99% ee) in 12 steps, as well as other botryanes, is described. The absolute configurations of these compounds have been unambiguously confirmed or reassigned accordingly. The key reactions in this study include an unusual rhodium-catalyzed intramolecular [4 + 2] cycloaddition and a biomimetic oxidative [3 + 2] cycloaddition based on our revised biogenetic pathway.
RESUMO
A typeâ II intramolecular oxidopyrylium-mediated [5+2] cycloaddition reaction allows the efficient and diastereoselective formation of various highly functionalized and synthetically challenging bridged seven-membered ring systems (such as bicyclo[4.4.1]undecane, bicyclo[4.3.1]decane, bicyclo[5.4.1]dodecane, and bicyclo[6.4.1]]tridecane). This simple, thermal, direct transformation has a broad substrate scope and is high yielding, with high functional-group tolerance and unique endo selectivity. The highly strained tricyclic cores of ingenol mebutate (picato) and cyclocitrinol are synthesized efficiently and diastereoselectively using this methodology.
Assuntos
Compostos Bicíclicos com Pontes/síntese química , Reação de CicloadiçãoRESUMO
Convergent approach: the total syntheses of (-)-flueggine A and (+)-virosaine B have been accomplished in a concise and convergent manner. Key steps in these approaches were relay ring-closing metathesis reactions for rapid construction of the key intermediates, and 1,3-dipolar cycloaddition reactions for the formation of the natural products.
Assuntos
Indolizinas/síntese química , Tropanos/síntese química , Produtos Biológicos/síntese química , Produtos Biológicos/química , Indolizinas/química , Estereoisomerismo , Tropanos/químicaRESUMO
The frequency of the L1014 F kdr mutation was determined in 14 field populations of house flies, Musca domestica L., with resistance factors at LD50 for pyrethrin/piperonyl butoxide and bioresmethrin/piperonyl butoxide from 4 to 29 and 2 to 98, respectively. A polymerase chain reaction test for identifying kdr homo- or heterozygote house flies was used to determine the frequency of kdr. The L1014 F allele was found in all populations tested. The frequency of kdr in the field populations was high and varied from 0.46 to 0.99. Eleven of the populations were in Hardy-Weinberg equilibrium, whereas two strains had higher number of heterozygotes than expected, indicating a possible heterozygote advantage. The frequency of kdr was strongly correlated with the reduced mortality observed in the bioassays with pyrethrum and bioresmethrin synergized by piperonyl butoxide. This indicates that kdr is a major mechanism for pyrethroid resistance in these field populations. Five field populations had resistance factors >25 and >10 for bioresmethrin/piperonyl butoxide and pyrethrin/piperonyl butoxide, respectively. The frequencies of kdr in these five populations varied from 0.89 to 0.99. The frequencies of kdr in the field populations showing no or a low level of resistance had frequencies of kdr from 0.46 to 0.75, which indicates that the L1014 F kdr allele is a fully recessive genetic trait in house flies. We have shown that the molecular diagnostic PASA method to determine the resistance phenotypes and the frequency of kdr is a powerful tool, which could be used to get information to make recommendations about pest and resistance management.