Ethyl retinoate

These compounds were converted to the corresponding all E and 9Z-retinoic acids via P-ionylideneacetaldehydes. Thus, the reaction with the lithium salt of (Et0)2P(0)CH2C(Me)=CHC00Et in THF made possible the C20 ester-complex. The complex was removed by CuCh in EtOH (98%) and saponification of the ethyl retinoate, the retinoic acids could be obtained all E 89%, 13Z 8% and 9Z 59%, 9Z,13Z 12%, respectively). 

Babler and Schlidt [86] described a route to a versatile C15 phosphonate, used for a stereoselective synthesis of all E retinoic acid and p-carotene. Base-catalyzed isomerization of the vinyl-phosphonate afforded the corresponding allyl-phosphonate as the sole product. Homer-Emmons olefination with ethyl 3-methyl-4-oxo-2-butenoate concluded the facile synthesis of all E ethyl retinoate. The C15 phosphonate was synthesized starting from the epoxide of P-ionone. Subsequent isomerization with MgBr2, afforded the C14 aldehyde in 93%... 

Bernard, M., Ford, W.T., and Nelson, E.C., Syntheses of ethyl retinoate with polymer-supported Wittig reagents, J. Org. Chem., 48, 3164, 1983. 

This group of natural compounds is also structurally diverse ranging from the simple dienes like a sex pheromone (4E,7Z)-4,7-tridecadienyl acetate or ( )- , )-coriolic acid through typical polyenes like the all-trans-stereomer of ethyl retinoate to the more complex, optically active calyculins A and B. In the total syntheses of polyenes presented below, the structurally complex phosphonate or bisphosphonate reagents were used in the Horner-Wittig olefination reactions solely or in combination with the Suzuki coupling. 

A stereoselective synthesis of all-trans-stereomer of ethyl retinoate (111) was reported by Babler and Schlidt [56] starting from the easily available -ionone 112 (Scheme 30). The key step of the synthesis was a base-catalyzed isomerization of the vinylphosphonate 113, which was obtained in the Horner-Wittig reaction of the aldehyde 114 and tetraethyl bisphosphonate, to give the allylic phosphonate 115 as the sole product. The Horner-Wittig reaction of the latter with ethyl trans-3-methyl-4-oxo-2-butenoate concluded a facile synthesis of the all-trans-polyenic retinoate 111. 

Derivatives of retinoic acids are named as carboxylic acid derivatives, e.g., ethyl retinoate (24) and A -ethylretinamide (25). 

When the UV spectrum of (40) is compared with that of ethyl retinoate (24), the hypsochromic shift indicates that the conjugation between the tetraene side chain and the ring double bond in (40) is slightly better than in (24), a fact readily explainable by the lack of the methyl group in (40) (Dawson et al., 1980). 

In a novel alkylating method that has been published, the dianion of carboxylic acid (177) was subjected, in a first step, to a nucleophilic addition reaction with the Cjo aldehyde ester (169) to give the unstable hydroxy acid (178) (Trost and Fortunak, 1981). The acetylated acid (179) smoothly underwent decarboxylative elimination to give ethyl retinoate (24). 

An attempt was made to synthesize the bicyclic retinoids (247) directly by Simmons-Smith cyclopropanation of ethyl retinoate (24). Only isomerized starting material was obtained (Dawson et aL, 1981b). It was therefore necessary to develop a separate, multistage procedure for the synthesis of (247). Initially, cyclopropanated p-cyclocitral (243) was reacted with the weakly nucleophilic anion of the phosphonate (244), generated by means of sodium hydride in di-methylsulfoxide. This procedure, too, failed to give the desired molecule (247), and the product obtained was merely the derivative (245) containing an expanded ring. 

The carbon skeleton of the naphthalene compounds (563) and (564), which are structurally analogous to ethyl retinoate (24) and retinaldehyde (2), was obtained via the ketone (562) (Akhtar et al., 1982). The aldehyde (564), which binds, as the chromophore, to opsin, was obtained by reducing the ethyl ester (563) with lithium aluminum hydride/aluminum chloride and finally oxidizing the product with manganese(IV) oxide. The trans double bond of methyl (all- )-... 

A Claisen-type condensation of ethyl retinoate (24) with the a-hydroxymethyl ketone (641) in the presence of lithium amide in tetrahydrofuran led to the enolized diketone (642), which when treated with an acid, underwent cyclization to give the butenolide (643) (Ito et aL, 1979b). 

Kaegi and DeGraw (1981) condensed the labeled aldehyde (Ib) with the phosphonate (XXIV) in a Homer-Emmons reaction. The phosphonate ester (XXIV) was synthesized by Homer-Emmons condensation of chloroacetone with triethyl phosphonoacetate followed by heating of the resulting 3-methyl-4-chlorocrotonate with triethyl phosphite at 150 C (Fujiwara et aL, 1962). The phosphonocrotonate (XXIV) was obtained as a 50 50 cis-trans mixture, but after condensation with the tritio aldehyde (la) in a phase-transfer medium (Piechuki, 1974), the ethyl retinoate (XXVa) so obtained was shown to be 85% trans by HPLC. Hydrolysis of the ester in alcoholic potassium hydroxide afforded the retinoic-11- H acid (Vlld), which was isolated by crystallization. 

The BASF workers reportedly made all-tran -retinoic acid by hydrolysis of ethyl retinoate-ll- H (XXV), which was prepared from a p-ionylidene ethyl-11- H phosphonium salt (XIX) and ethyl p-formylcrotonate (XX), presumably in an inert solvent. 

Ethyl retinoate was made with almost complete retention of deuterium, using the dideutero phosphonium salt (XIX), w-butyllithium in THF, and ethyl formyl crotonate (XX). 

E8 Retinoic acid ethyl ester [3899-20-5] Ethyl retinoate... 

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