The total synthesis of an anticancer (anaplastic thyroid) natural lipid mycalol has been accomplished for the first time. Synthesis of originally proposed structure necessitated the revision of structure in which the position of acetate group moved from C20 to C19 and a change in stereochemistry of the glycerol unit.
Therapeutic options for brain infections caused by pathogens with a reduced sensitivity to drugs are limited. Recent reports on the potential use of linezolid in treating brain infections prompted us to design novel compounds around this scaffold. Herein, we describe the design and synthesis of various oxazolidinone antibiotics with the incorporation of silicon. Our findings in preclinical species suggest that silicon incorporation is highly useful in improving brain exposures. Interestingly, three compounds from this series demonstrated up to a 30-fold higher brain/plasma ratio when compared to linezolid thereby indicating their therapeutic potential in brain associated disorders.
A simple and efficient synthesis of functionalized cis-hydrindanes and cis-decalins was achieved using a sequential Diels-Alder/aldol approach in a highly diastereoselective manner. The scope of this method was tested with a variety of substrates and was successfully applied to the synthesis of two natural products in racemic form. The highlights of the present work provide ready access to 13 new cis-hydrindanes/cis-decalins, a protecting group-free total synthesis of an insect repellent Nootkatone, and the first synthesis of a Noreremophilane using the shortest sequence.
Concise and protecting-group free synthesis of ent-palmyrolide A and (-)-cis-palmyrolide A were achieved starting from commercially available (S)-citronellal. The key fragment of palmyrolide A, "(5S,7S)-7-hydroxy-5,8,8-trimethylnonanamide", which makes up the most challenging part of the target molecule, was prepared in just three steps. A plausible mechanism for the trans-cis isomerization of the double bond in the macrocycle has been investigated.
Here, we disclose novel mosquito-repellent
synthetic hydrindanes
based on noreremophilanes and nardoaristolone B which show increased
activity against adult females of Aedes aegypti. The noreremophilanes and nardoaristolone B with hydrindane skeleton
are structurally related to nootkatone with decalin skeleton, a well-studied
natural product extracted from a grape fruit. Out of our library of
compounds synthesized based on the noreremophilanes and nardoaristolone
B scaffolds, NDS-100598 (compound 20) exhibits higher
repellent and knock-down effects at a very low concentration (0.25
mg/cm2), while a few analogues showed considerably enhanced
activity compared to racemic nootkatone. This is the first report
documenting insect-repellent and knock-down activity of the noreremophilanes
class of compounds.
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