102679-55-0Relevant articles and documents
Macrodiolide Diversification Reveals Broad Immunosuppressive Activity That Impairs the cGAS-STING Pathway
Biltoft, Mette,Jakobsen, Martin R.,Jennet, Kira M.,Kristensen, Tobias F.,Liu, Han,Ottosen, Rasmus N.,Poulsen, Thomas B.,Svenningsen, Esben B.
, p. 18734 - 18741 (2021)
The development of new immunomodulatory agents can impact various areas of medicine. In particular, compounds with the ability to modulate innate immunological pathways hold significant unexplored potential. Herein, we report a modular synthetic approach to the macrodiolide natural product (?)-vermiculine, an agent previously shown to possess diverse biological effects, including cytotoxic and immunosuppressive activity. The synthesis allows for a high degree of flexibility in modifying the macrocyclic framework, including the formation of all possible stereoisomers. In total, 18 analogues were prepared. Two analogues with minor structural modifications showed clearly enhanced cancer cell line selectivity and reduced toxicity. Moreover, these compounds possessed broad inhibitory activity against innate immunological pathways in human PBMCs, including the DNA-sensing cGAS-STING pathway. Initial mechanistic characterization suggests a surprising impairment of the STING-TBK1 interaction.
Nozoe et al.
, p. 4675 (1965)
Stereoselective total synthesis of (-)-pyrenophorol
Yadav,Subba Reddy,Subba Reddy
, p. 5984 - 5986 (2009)
An efficient stereoselective total synthesis of (-)-pyrenophorol 1 is described. The key steps involved in this synthesis are hydrolytic kinetic resolution (HKR), MacMillan α-hydroxylation, Horner-Wadsworth-Emmons (HWE) reaction, and Mitsunobu cyclization
Asymmetric hydroformylation-initiated tandem sequences for syntheses of (+)-patulolide C, (-)-pyrenophorol, (+)-decarestrictine L, and (+)-prelog djerassi lactone
Risi, Roberto M.,Maza, Andrew M.,Burke, Steven D.
, p. 204 - 216 (2016/09/09)
Four different Rh-catalyzed asymmetric hydroformylation (AHF) tandem reactions have been developed in the context of the total syntheses of (+)-patulolide C, (-)-pyrenophorol, (+)-decarestrictine L, and (+)-Prelog-Djerassi lactone. A total synthesis of (+)-patulolide C has been accomplished in three steps utilizing a Rh(I)-catalyzed Z-selective anti-Markovnikov hydroacetoxylation of a known alkyne to give a Z-enol acetate with excellent selectivity. An AHF/intramolecular Wittig olefination cascade was utilized to set the C4-hydroxyl stereochemistry, E-olefin geometry, and form the macrolactone. In addition, both (-)-pyrenophorol and (+)-decarestrictine L have been synthesized from the enantiomeric (4R)- and (4S)-4-(tert-butyldimethylsiloxy)-1-pentyne in five and four steps, respectively. These syntheses feature Ru(II)-catalyzed Z-selective anti-Markovnikov hydroacetoxylation of terminal alkynes followed by AHF/Wittig olefination sequences to rapidly establish functionality and stereogenicity. A synthesis of (+)-Prelog-Djerassi lactone was accomplished in three isolations from the known 1-vinyl-4-methyl-2,6,7-trioxabicyclo[2.2.2]-octane ortho ester. An AHF/crotylation tandem sequence has been developed to set the C2-C4 stereochemistry. An asymmetric hydrogenation was employed to set the C6 stereochemistry, resulting in an especially efficient enantioselective synthesis from achiral starting material. In summary, these syntheses have greatly improved efficiency in terms of atom-economy, catalytic stereoselective transformations, inexpensive reagents, step-counts, and overall yield when compared with previous synthetic attempts.
