Synthesis of 3-Aminomethyl-2-aryl- 8-bromo-6-chlorochromones

Abstract

[reaction: see text] An efficient synthetic route to Cbz-protected 3-aminomethyl-2-aryl-8-bromo-6-chlorochromones has been developed. 3-Aryl-1-(3-bromo-5-chloro-2-hydroxyphenyl)-2-propen-1-one or 2-aryl-8-bromo-6-chlorochroman-4-one could be reacted under Mannich conditions yielding 2-aryl-8-bromo-6-chloro-3-methylenechroman-4-one, which was further converted to the target compound via an aza-Michael reaction followed by an SeO(2) oxidation. This procedure represents a new method to introduce a primary aminomethyl group at the 3-position of a 2-arylchromone scaffold. The Cbz-protected 3-aminomethyl-2-aryl-8-bromo-6-chlorochromones can, e.g., be used in the synthesis of chromone-based beta-turn peptidomimetics.

Synthesis and Evaluation of Substituted Chroman-4-one and Chromone Derivatives as Sirtuin 2-Selective Inhibitors

“…32 Recently, we have also developed chromone/chroman-4-one-based β-turn peptidomimetics. 31,33 In the present study we report substituted chromone and chroman-4-one derivatives as potent and highly selective SIRT2 inhibitors.…”

“…27 We have put considerable effort into the development of synthetic strategies for this class of compounds resulting, for example, in an efficient synthetic route to 2-alkyl-substituted chroman-4-ones. 28 The incorporation of various functional groups to furnish highly substituted structures have successfully been conducted through different Pd-mediated cross-coupling reactions, 29,30 through Mannich reactions, 31 and via a SmI 2 –KHMDS-mediated Reformatsky type reaction. 32 Recently, we have also developed chromone/chroman-4-one-based β-turn peptidomimetics.…”

Acidic rearrangement of benzyl group in flavone benzyl ethers and its regioselectivity

“…Recently, this reaction was successfully used by the Seoane group and us to totally synthesize benzyl-substituted flavone compounds and benzyl-substituted flavanone compounds [9,12]. Compared to the methods used previously [13][14][15][16], the method using this rearrangement reaction offers simple protocols and high yields.…”

Synthetic strategies in the construction of chromones

“…In 2007, Luthman and coworkers [99] developed an efficient synthetic route to Cbz‐protected 3‐aminomethyl‐2‐aryl‐8‐bromo‐6‐chlorochromones 147 (Scheme ). In their synthetic route, 3‐Aryl‐1‐(3‐bromo‐5‐chloro‐2‐hydroxyphenyl)‐2‐propen‐1‐one 144 was reacted under Mannich conditions yielding 2‐aryl‐8‐bromo‐6‐chloro‐3‐methylenechroman‐4‐one 145 , which was further converted to the target compound 147 via an aza‐Michael reaction followed by an SeO 2 oxidation [100–103].…”