biostudies-literatureGhosh AKPurdue UniversityNational Institute of General Medical SciencesNIGMS NIH HHS5187-5198https://www.ebi.ac.uk/biostudies/studies/S-EPMC5972027biostudies-literatureUnknown83(9)Thailanstatin A has been isolated recently from the fermentation broth of B. thailandensis MSMB43. We describe here an enantioselective convergent synthesis of thailanstatin A methyl ester and evaluation of its splicing activity. Synthesis of both highly functionalized tetrahydropyran rings were carried out from commercially available tri- O-acetyl-d-glucal as the key starting material. Our convergent synthesis involved the synthesis of both tetrahydropyran fragments in a highly stereoselective manner. The fragments were then coupled using cross-metathesis as the key step. The synthesis of the diene subunit included a highly stereoselective Claisen rearrangement, a Cu(I)-mediated conjugate addition of MeLi to set the C-14 methyl stereochemistry, a reductive amination reaction to install thThe Journal of organic chemistryEnantioselective Synthesis of Thailanstatin A Methyl Ester and Evaluation of in Vitro Splicing Inhibition.PMC5972027GM122279T32 GM008646R37 GM053386R01 GM122279Nie SMacRae AJJurica MSVeitschegger AMGhosh AKRelitti NfalseEnantioselective Synthesis of Thailanstatin A Methyl Ester and Evaluation of in Vitro Splicing Inhibition.Thailanstatin A has been isolated recently from the fermentation broth of B. thailandensis MSMB43. We describe here an enantioselective convergent synthesis of thailanstatin A methyl ester and evaluation of its splicing activity. Synthesis of both highly functionalized tetrahydropyran rings were carried out from commercially available tri- O-acetyl-d-glucal as the key starting material. Our convergent synthesis involved the synthesis of both tetrahydropyran fragments in a highly stereoselective manner. The fragments were then coupled using cross-metathesis as the key step. The synthesis of the diene subunit included a highly stereoselective Claisen rearrangement, a Cu(I)-mediated conjugate addition of MeLi to set the C-14 methyl stereochemistry, a reductive amination reaction to install th2018-01-01T00:00:00Z2018 May2025-04-22T01:37:35.14Z2019-06-06T23:03:51ZS-EPMC59720272969698010.1021/acs.joc.8b00593