The synthesis of “vitamin A acid”, a biologically active substance

Abstract

By dehydration and subsequent saponification of the reaction product obtained from @onone and y-bromocrotonic ester we prepared p-ionylidene crotonic acid 111, which substance was transformed into the "cis ketone" IV by means of lithium methyl. From , this ketone we prepared "vitamin A add" VII, by means of a R e f o r m a t s k i reaction with methylbromoacetate. This substance proved to have a strong vitamin A activity.Since the establishment of the structure of vitamin A 4 ) . several attempts have been made to synthesize this important substance. A review of the literature up to 1943 has been given by H e i l b r o n , J o n e s and

75 Years of Vitamin A Production: A Historical and Scientific Overview of the Development of New Methodologies in Chemistry, Formulation, and Biotechnology

“…However, it took another seven years before other research groups could publish successful syntheses of vitamin A. Three groups published different approaches within a short period of time. ,− Arens and van Dorp from the company Organon described the synthesis of vitamin A acid 6 from β-ionone 7 via C 18 -ketone 16 and of retinal 5 following a similar route applying ethoxy acetylene as a key building block (Scheme ). Milas reported the synthesis of vitamin A methyl ether (and vitamin A esters) starting from β-ionone 7 , which was elongated to the C 14 -aldehydes 17 or 18 and subsequently to C 16 -propargylic alcohol 23 , which was coupled in a Grignard reaction with a C 4 -building block 24 to a C 20 -compound 27 (Scheme ).…”