General Method for the Synthesis of (−)-Conduritol C and Analogs from Chiral Cyclohexadienediol Scaffolds

Abstract

An efficient and facile general method for the synthesis of conduritol C analogs, taking advantage of an enantioselective biocatalysis process of monosubstituted benzenes, is described. The absolute stereochemical patterns of the target molecules (−)-conduritol C, (−)-bromo-conduritol C, and (−)-methyl-conduritol C were achieved by means of chemoenzymatic methods. The stereochemistry present at the homochiral cyclohexadiene-cis-1,2-diols derived from the arene biotransformation and the enantioselective ring opening of a non-isolated vinylepoxide derivative permitted the absolute configuration of the carbon bearing the hydroxyl groups at the target molecules to be established. All three conduritols and two intermediates were crystallized, and their structures were confirmed by X-ray diffraction. The three conduritols and intermediates were isostructural. The versatility of our methodology is noteworthy to expand the preparation of conduritol C analogs starting from toluene dioxygenase (TDO) monosubstituted arene substrates.

Achievements, Challenges, and Scope of Thirty Years of Work on the Biotransformation of Arenes and Their Synthetic Applications

“…For the preparation of conduritol C and analogs, we took advantage of one of the methodologies extensively studied and used in our lab, the hydroxyhalogenation of the cyclohexadiendiols that we described in b2) [35] . Methyl‐conduritol C was easily prepared form the major iodohydrine obtained from the toluene derived diol, [91] as shown in Scheme 25.…”

Sequential enzymatic and electrochemical functionalization of bromocyclohexadienediols: Application to the synthesis of (−)-conduritol C

“…)-5-bromocyclohex-5-ene-1,2,3,4-tetraol (4) 15 The crude mixture of 6 batches was combined and filtered for removal of the catalyst, and the flasks were washed with MeOH to remove product residues and combined with the MTBE filtrate and concentrated in vacuo. The obtained white crude product was adsorbed in 24% deactivated silica gel and purified by flash column chromatography (EtOAc:Hex:MeOH 8:1:1) to yield tetrol as a white solid 4 (88 mg, 13%).…”