Vitamin A Retinol
Tretinoin Synthesis

Tretinoin (all-trans retinoic acid) is industrially synthesized via stereospecific Wittig reactions combining a substituted triphenylphosphonium salt with β-formyl crotonic acid derivatives in the presence of an alkali, followed by catalytic isomerization using palladium or rhodium compounds to achieve the desired all-trans configuration.

Industrial Production Steps

Wittig Reaction: Reacting a C15-triphenylphosphonium salt with a C5 aldehyde component (like β-formyl crotonic acid) under basic conditions to build the carbon skeleton.

Isomerization: Adjusting the reaction pH and introducing a noble metal catalyst (palladium or rhodium) to convert intermediate cis-isomers directly into the bioactive all-trans form without isolating intermediate products.

Purification: Crystallization from solvents like absolute ethanol under strict protection from light and oxygen to yield high-purity tretinoin.