Re₂O₇‐Mediated Dehydrative Cyclization Reactions: Total Synthesis of Herboxidiene and Its 12‐Desmethyl Analogue

Abstract

Re2O7 catalysis effects efficient and stereoselective dehydrative cyclization reactions from monoallylic diols, with stereocontrol arising from thermodynamic equilibration. This method was applied to a rapid synthesis of the spliceosome inhibitor herboxidiene. The route was also utilized for the synthesis of an analog that highlights the importance of a single methyl group in biasing the conformation in the acyclic region of the molecule.

Perrhenate Esters as Intermediates in Molecular Complexity-Increasing Reactions

“…This reaction initially generates a mixture of diastereomers that converged to the thermodynamically preferred product after gentle heating. 30 Qi Qin demonstrated numerous examples of this experimentally facile and atom-economical cyclization process. Highlights among these include the conversion of triol 55 into 56, in which each hydroxy group serves a different role (one as a nucleophile, one as a leaving group, and one as a spectator), and the transformation of 57 into 58, in which the presence of an additional stereocenter in the product is not detrimental to the cyclization efficiency.…”

A Comprehensive Overview of Structure‐Activity Relationships of Small‐Molecule Splicing Modulators Targeting SF3B1 as Anticancer Agents

“…The cytotoxic evaluation against HeLa cells revealed that the absence of the C12 methyl group induced at least a 40-fold drop in potency relative to herboxidiene. [76] A carbohydrate-derived analogue (91) was active in CLL-B cells (IC 50 = 153.0 nM) with~3-fold reduction of activity as compared to FD-895 (IC 50 = 54.1 nM). Compound 91 also exerted the effects on inducing intron retention and modulating alternative splicing in CLL-B cells, which was comparable to that of FD-895.…”

“…Floreancig group fulfilled the synthesis of C12 desmethylherboxidiene ( 90 ). The cytotoxic evaluation against HeLa cells revealed that the absence of the C12 methyl group induced at least a 40‐fold drop in potency relative to herboxidiene [76] . A carbohydrate‐derived analogue ( 91 ) was active in CLL‐B cells (IC 50 =153.0 nM) with ∼3‐fold reduction of activity as compared to FD‐895 (IC 50 =54.1 nM).…”

Diarylmethane synthesis through Re2O7-catalyzed bimolecular dehydrative Friedel–Crafts reactions

“…Our studies in the applications of Re 2 O 7 to allylic alcohol transposition reactions5,6 resulted in a new dehydrative cyclization protocol in which allylic cations react with pendent hydroxy groups 7,8. Re 2 O 7 proved to be superior to Brønsted acids for promoting these processes, leading us to speculate that it could be an effective catalyst for enabling bimolecular dehydrative coupling reactions.…”