Efficient ortho-formylation in vitamin E series, application to the semi-synthesis of natural 5- and 7-formyl-δ-tocotrienols revealing an unprecedented 5-bromo-7-formyl exchange

Semisynthetic Vitamin E Derivatives as Potent Antibacterial Agents against Resistant Gram‐Positive Pathogens

“…Subsequently, an aldehyde function was selected as a precursor of the carboxylic acid group. Formylation of 1 a to 5 a , following the previously reported procedure afforded 1 c to 5 c with yields ranging from 31 to 90 % [29] …”

“…In a first strategy, semisynthesis of 6-hydroxychroman-5-carboxylic acids required the C-5 bromination of the vitamin E derivatives 1 a to 5 a, to afford compounds 1 b to 5 b as previously reported (Scheme 1). [29] However, halogen-metal exchange and electrophilic substitution as described by Lambert et al [30] were unsuccessful. Subsequently, an aldehyde function was selected as a precursor of the carboxylic acid group.…”

“…Formylation of 1 a to 5 a, following the previously reported procedure afforded 1 c to 5 c with yields ranging from 31 to 90 %. [29] Prior embarking on the oxidation of the aldehyde function of 1 c and 2 c, phenolic group was protected as acetates 1 e and 2 e to prevent formation of quinonic derivatives. [31] Formyl oxidation under Pinnick conditions and hydrolysis of the protecting group led to final 6-hydroxychroman-5-carboxylic acids 1 g and 2 g with 52 and 24 % yield over four steps starting from natural δ-T and δ-T3.…”

Exploration of Long-Chain Vitamin E Metabolites for the Discovery of a Highly Potent, Orally Effective, and Metabolically Stable 5-LOX Inhibitor that Limits Inflammation

“…Formyl derivatives are key intermediates to access a wide variety of functionalized polyphenols ( e.g ., coumarins, chalcones). Therefore, a MgCl 2 -mediated formylation was applied to vitamin E derivatives from different series (tocopherol, tocotrienol, garcinoic acid, amplexichromanol), leading to 2 , 3 , 7 , 8 , 33 , 34 , and 47 ( 38 ) ( Scheme 2 ). Benzyl alcohol 46 was isolated due to an incomplete redox process ( Scheme 3 ).…”

“…To a solution of aldehyde 3 ( 38 ) (66 mg, 0,16 mmol, 1.0 equiv) in 3 mL of distilled THF at −5 °C under a nitrogen atmosphere was added dropwise n -BuLi 1.6 M in hexane (200 μL, 0.30 mmol, 1.95 equiv). The reaction mixture was stirred for 2 h at −5 °C.…”