37244-00-1Relevant 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 (2021/07/19)
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.
Concise Total Synthesis of (?)-Vermiculine through a Rhodium-Catalyzed C2-Symmetric Dimerization Strategy
Steib, Philip,Breit, Bernhard
, p. 3532 - 3535 (2019/02/19)
A short and efficient synthesis of the C2-symmetric antibiotic (?)-vermiculine by utilizing an enantioselective catalytic one-step dimerization methodology as key-step to construct the core structure is reported. The late-stage modifications feature a double metathesis homologation followed by a double Wacker-type oxidation. These key-steps allowed the synthesis of vermiculine in only seven steps, starting from commercially available building blocks.
Total Synthesis of (-)-Vermiculine
Noda, Atsushi,Aoyagi, Sakae,Machinaga, Nobuo,Kibayashi, Chihiro
, p. 8237 - 8240 (2007/10/02)
Macrodiolide (-)-vermiculine has been synthesized via intramolecular Mitsunobu reaction utilizing a C2 symmetrical diepoxide chiral synthon.
SYNTHESIS OF dl-VERMICULINE VIA CONTROL OF OLEFIN FORMATION
Wakamatsu, Takeshi,Yamada, Satoshi,Ban, Yoshio
, p. 309 - 312 (2007/10/02)
The synthesis of the macrodiolide antibiotic vermiculine 1 has been achieved starting from the enediol(trimethylsilyl enol ether via the macrocyclization of hydroxycarboxylic acid followed by the formation of the requisite trans double bonds.
ALTERNATIVE SYNTHESIS OF (+/-)-VERMICULIN
Traverso, Giorgio,Pirillo, Demetrio,Gazzaniga, Andrea
, p. 461 - 464 (2007/10/02)
The synthesis of (+/-)-vermiculin, 1, is reported.The key step is the condensation of the formyl ester 13 with the acetoacetic dianion to diester 15.
