Cyclohexadiene-trans-diols as versatile starting material in natural product synthesis: short and efficient synthesis of iso-crotepoxide and ent-senepoxide

Abstract

A new synthesis of ent-senepoxide and iso-crotepoxide starting from microbially produced(+)-trans-2,3-dihydroxy-2,3-dihydrobenzoic acid via regio- and stereoselective epoxidation is described.

Diversity‐Oriented Production of Metabolites Derived from Chorismate and Their Use in Organic Synthesis

“…We showed in earlier work that 2,3‐ trans ‐CHD ( 5 ) is a beneficial building block for the synthesis of natural product derivatives by stereo‐ and regioselective epoxidation and dihydroxylation 13. 14 In a similar approach, 3,4‐ trans ‐CHD ( 9 ) was regio‐ and stereoselectively functionalized on each of the two carbon–carbon double bonds. Steric hindrance and induced preferential conformations are the key issues for stereoselectivity.…”

β- and σ-Amino acids (2,3- and 3,4-trans-CHA) as catalysts in Knoevenagel condensation and asymmetric aldol reactions

“…While the two amino acids 2,3-trans-CHA (2) and 3,4-trans-CHA (4) proved to be just as good as the L-proline catalyst with respect to enantioselectivity, they intrinsically possess several advantages. As we and others have shown for 2 and 4, and for the respective diols 2,3-trans-CHD (3) and 3,4-trans-CHD (5), 39,41,48,49 the carboxylate moiety and the vicinal diol or amino alcohol moieties can be protected selectively. The 1,3-diene system of these compounds can be modified highly specifically through oxidative or reductive processes (e.g., epoxidation, dihydroxylation, selective hydrogenation), as well as via pericyclic reactions such as Diels-Alder and hetero-Diels-Alder additions (Scheme 5).…”

“…34 The shikimate pathway is an instructive example of diversity-oriented biosynthesis of a wide spectrum of natural products (Scheme 1). 35,36 Shikimate-and chorismate-derived metabolites and their enzymatic transformations have been applied in synthesis, notably by Frost et al 37 and by Müller et al [38][39][40][41][42] These multifunctionalized and conformationally restricted natural products could serve as valuable chiral auxiliaries, chiral ligands, and organocatalysts in asymmetric transformations. Here, we focus on the production of the microbial nonproteinogenic amino acids 2,3-trans-CHA and 3,4-trans-CHA (4), and derivatives thereof, and their use as potent (organo)catalysts.…”

Organocatalytic Asymmetric 1,6‐Addition Reactions

“…After synthesis of the common trans ‐CHD intermediate 126 ( via 127 and 128 ) different amounts of m CPBA yielded either single or double epoxidation. One equivalent led to the monoepoxidized (+)‐senepoxide [(+)‐ 30 , via 129 ] while 2.5 equivalents yielded the diepoxidized (+)‐ 125 ( via 130 ) (Scheme ) 64…”