Chemoenzymatic Access to Versatile Epoxyquinol Synthons

Abstract

The enantiomerically pure and readily available metabolites 10-12 have been converted over four simple steps into the epoxyquinol derivatives 22-24, respectively. Compounds 23 and 24 or their immediate precursors have been exploited in efficient total syntheses of (-)-bromoxone (ent-1), (-)-epiepoformin (ent-2), (-)-harveynone (4), (+)-panepophenanthrin (6), and (+)-hexacyclinol (9).

An Enantioselective Synthesis of the Epoxyquinol (+)‐Isoepiepoformin

“…In keeping with earlier observations, [2,3] reaction of compound 7 with freshly prepared sodium methoxide in THF at ambient temperatures gave epoxide 8, which was obtained as a white, crystalline solid in 99 % yield. The selectivity of this epoxide-forming step is attributed to the more favorable orientation of the non-allylic hydroxy group (over its allylic counterpart) for participation in the required internal nucleophilic displacement reaction.…”

“…Several attempts to improve the selectivity of this reductive cleavage process, including those involving an examination of variations in reaction solvent and temperature as well as the nature of the reducing agent, failed. Treatment of the 2.5:1 mixture of monoethers 4 and 5 with N-bromosuccinimide (NBS) in wet THF under conditions used in our earlier studies [2,3] Scheme 1.…”

“…More broadly speaking, this work highlights the continued utility of microbially derived and enantiomerically pure cis-1,2-dihydrocatechols as starting materials in chemical synthesis. [2][3][4] Supporting Information (see footnote on the first page of this article): Detailed experimental procedures, 1 H NMR, 13 C NMR, IR spectroscopic together with mass spectrometric data for compounds 1, 3-5 and 7-12, as well as single-crystal X-ray analyses data for compounds 9 and 11 and an ORTEP of compound 11.…”

“…Recently we reported [2,3] the ready preparation of a series of enantiomerically pure epoxyquinol synthons from cis-1,2-dihydrocatechols of the general form 2 (X = Cl, Br or I) -the latter compounds being available in large quantity and enantiomerically pure form through the whole-cell biotransformation of the corresponding halobenzene. [4] The acquisition of these synthons enabled us to develop highly abbreviated total syntheses of (-)-bromoxone, (-)-bromoxone acetate, (-)-epiepoformin, (-)-harveynone, (+)-panepophenanthrin, (+)-hexacyclinol and (-)-tricholomenyn A, synthetic sample of compound 1 match those reported in the literature for the natural product and thereby confirm the structure assigned to the latter.…”

Data Mining for Three-Dimensional Organic Dirac Materials: Focus on Space Group 19

“…We point out the first real material examples in the class of three-dimensional organic crystals hosting isolated Dirac nodes in the electronic structure: C 6 H 7 ClO 3 25 , C 10 H 10 Br 2 Cl 3 NO 2 26 , C 12 H 13 NO 2 27 , C 13 H 12 N 2 O 28 , C 9 H 10 F 3 NO 29 , and C 10 H 12 BrNO 30 . It will be shown that the found Dirac nodes are a consequence of the orthorhombic crystal structure of the space group P 2 1 2 1 2 1 (#19).…”