Synthesis of oxygenated 4-arylisoflavans and 4-arylflavans

X‐Ray Crystallography and Free Energy Calculations Reveal the Binding Mechanism of A2A Adenosine Receptor Antagonists

“…Briefly,t he key 2-hydroxyphenyl ketones 3 were obtained by either the Hoesch method [30] or Claisen condensation, [36] employing phenols 1 or esters 6 and thiazole derivatives 2a and 2b as reactive precursors,r espectively. Tr eatment of ketones 3 with orthoesters (formate or acetate) enabled the efficient chromone core formation, [37] thus defining the substituent pattern at position 2( Ho rM e). Finally,the required acetates were prepared by reaction of the corresponding phenols with acetyl chloride.The full synthetic methodology is provided in the Supporting Information.…”

Chemoenzymatic Stereoselective Synthesis of trans-Flavan-4-ols via Lipase-Catalyzed Kinetic Resolutions

“…Traditionally, the most straightforward approaches to produce racemic flavan-4-ols consist of reductions in flavanones and flavones, selectively leading to the corresponding cis-isomers as major products. In this context, the use of sodium borohydride [10,11] or catalytic hydrogenation employing palladium on charcoal [12,13] have afforded a series of racemates in high yields. The preferential formation of cis-flavan-4-ols can be easily explained considering that the hydride or catalyst would approach the flavanone from the less hindered face, opposite the aromatic group at C-2, favoring the addition of the hydride or hydrogen to the carbonyl from that face.…”

“…Among the enzymatic methods, the desymmetrization of flavanones through bioreduction processes and the kinetic resolution of flavanols and their corresponding acetates using hydrolases are the most demanding strategies. The practical application of redox processes is usually hampered by the formation of complex product mixtures, low isolated yields, and working with very low substrate concentrations [13,[17][18][19]22], while Similarly, the stereoselective synthesis of cis-flavan-4-ol enantiomers has received much more attention than the one of its trans-analogues, metal [16][17][18] and enzyme catalysis [15,[19][20][21][22][23][24] facilitating the preparation of chiral flavan-4-ols with excellent stereoselectivity levels. Among the enzymatic methods, the desymmetrization of flavanones through bioreduction processes and the kinetic resolution of flavanols and their corresponding acetates using hydrolases are the most demanding strategies.…”

“…Among the enzymatic methods, the desymmetrization of flavanones through bioreduction processes and the kinetic resolution of flavanols and their corresponding acetates using hydrolases are the most demanding strategies. The practical application of redox processes is usually hampered by the formation of complex product mixtures, low isolated yields, and working with very low substrate concentrations [13,[17][18][19]22], while the use of lipases as biocatalysts have provided better results for practical applications [19][20][21]. For instance, Kasahara and co-workers reported the hydrolysis of 2-phenylchroman-4yl acetate using the lipase from Pseudomonas cepacia (PSL) that allows the recovery of (2R,4R)-alcohol and (2S,4S)-acetate with high enantiomeric excess values (93% and 95% ee, respectively) [19].…”

X-Ray Crystallography and Free Energy Calculations Reveal the Binding Mechanism of A2A Adenosine Receptor Antagonists

“…Briefly, the key 2-hydroxyphenyl ketones 3 were obtained by either the Hoesch method 27 or Claisen condensation, 35 employing phenols 1 or esters 6 and thiazole derivatives 2a and 2b as reactive precursors respectively. Treatment of ketones 3 with orthoesters (formate or acetate) enabled the efficient chromone core formation, 36 thus defining the substituent pattern at position 2 (H or Me). Finally, the required acetates were prepared by reaction of the corresponding phenols with acetyl chloride.…”