The Application of Dioxygenase‐Based Chemoenzymatic Processes to the Total Synthesis of Natural Products

Abstract

This Minireview describes the exploitation of certain enzymatically derived, readily accessible, and enantiomerically pure cis‐1,2‐dihydrocatechols as starting materials in the chemical synthesis of a range of biologically active natural products, most notably sesquiterpenoids and alkaloids.

Troponoid Compounds as Therapeutic Agents and as Targets and Templates for Chemical Synthesis

“…We have also developed alternative means for generating and then ring-expanding σ-homo- o -benzoquinones, as demonstrated in the synthesis of stipitatic acid ( 16 ) (Scheme 27 ). 102 Thus, cis -1,2-dihydrocatechol ( 199 ), which is obtained at multi-gram scale through the whole-cell biotransformation of benzene, 103 can be converted, under carefully controlled conditions, 104 into the corresponding acetonide 200 . This acetonide is then subjected to reaction with dibromocarbene to afford adduct 201 in a completely stereocontrolled manner.…”

Design and Synthesis of C-1 Methoxycarbonyl Derivative of Narciclasine and Its Biological Activity

“…The more elaborate synthesis of the C-ring coupling precursor, which contains all the necessary chiral centers of the final product, begins with the enzymatic dihydroxylation of ortho-dibromobenzene (13, Scheme 3). This is accomplished by a whole-cell fermentation process [20] with a recombinant strain of E. coli JM109 (pDTG601A [21]) that over-expresses toluene dioxygenase and was successfully used for the oxidative de-aromatization of various aromatic substrates [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] employed in the synthesis of natural products. Once dibromodiene diol 12 was obtained, it was subjected to acetonide protection and a nitroso Diels-Alder reaction in a one-pot procedure to form the bicyclic oxazine 21.…”

“…22: R f = 0. [1,3]dioxol-4-yl)carbamate (23) Imidazole (136 mg, 2.0 mmol) and TBSCl (452 mg, 3.0 mmol) were added to a solution of alcohol 22 (402 mg, 1.0 mmol) in 10 mL of DCM at room temperature. After the complete consumption of the starting material was observed by TLC (approximately 24 h), the reaction mixture was quenched with a saturated aqueous solution of NH 4 Cl (10 mL) and extracted with DCM (3 × 10 mL).…”

Shaping Molecular Landscapes: Recent Advances, Opportunities, and Challenges in Dearomatization

“…Transformations of benzene derivatives that result in permanent loss of aromaticity have since become a cornerstone of synthetic methodology; over the last century, dearomative reactions such as hydrogenation, 2 the Birch reduction, 3 and dearomatizations of phenols 4 have revolutionized the way chemists make molecules (Figure 1). 5 More sophisticated methods employing biocatalysis, 6 transition metals, 7,8 and arenophiles 9 have increased the complexity of building blocks accessible from simple benzene derivatives. Heteroaromatic compounds, which possess lower resonance stabilization than carbogenic arenes, have an equally rich canon of robust dearomative transforms.…”