Retinoic acid epoxide

Tetraterpene derivatives Retinoic acid epoxide (D 6.5) Vertebrates (Unknown) Differentiation of epithelia... 

D 3.2.6 carotenoids and vitamin A, which are transformed to retinoic acid epoxide, D 6.5 and under certain conditions also the vitamins D, which are the precursors of hydroxylated vitamin D derivatives, D 6.4.9. 

Panzella, L, Manini, P, Napolitano, A, and d Ischia, M, 2004. Free radical oxidation of (E)-retinoic acid by the Fenton reagent Competing epoxidation and oxidative breakdown pathways and novel products of 5,6-epoxyretinoic acid transformation. ChemRes Toxicol 17, 1716-1724. 

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%... 

Some compounds normally in body are oxidized by P450 2C9, including linoleic acid (epoxidation) and vitamin A (all-tran.s-retinoic acid, 4-hydroxylation) , although the physiological significance is unknown. 

Several papers have described the synthesis of epoxyretinoids. The 5,6-epoxides of fmns-retinal (88) and its (9Z)-, (IIZ)-, and (13Z)-isomers were prepared by direct epoxidation of retinal with w-chloroperbenzoic acid. The 7,8-epoxides (89) of retinal, retinol, and retinoic acid and its methyl esters were synthesized from the jS-ionone epoxide (90). The exceedingly labile methyl 13,14-epoxy-13,14-dihydroretinoate (91) was made by addition of the epoxyaldehyde (92) to the phosphorane (93). Chromogen 574 , a product of the epoxidation of retinol first described in 1945, has now been identified as the... 

Retinoic acid 5,6-epoxidation was catalysed by human blood cells but not by human plasma, and purified human haemoglobin also catalysed the ep-oxidation of retinoic acid to 5,6-epoxyretinoic acid (Iwahashi et al. 1985). 

The compound (75) reacted with an excess of a peracid to give the epoxide (76), whereas oxidation with chromium(VI) oxide gave the carbonyl compound (77). The epoxidized esters of (all- )-retinoic acid (3), namely, the 11,12-epoxyretinoid (190) and the 13,14-epoxyretinoid (493), are very reactive intermediates and have hence been used in syntheses. 

Chien and Amin (1980) have reported the preparation of 5,6-epoxy-5,6-dihydroretinoic acid (LXIII) labeled with tritium in position 11. The compound was readily obtained from the tritiated retinoic acid by epoxidation with mono-perphthalic acid (Fig. 17). 

However, in retinoic acid-repleted animals the 5,6-epoxide could not be detected at 3 h after injection of [ Hjretinoic acid, possibly owing to the induction of retinoic acid metabolism that lowered the amount of available retinoic acid for subsequent epoxidation (Roberts et al., 1979b Napoli and McCormick, 1981) or to the repressed synthesis of the [ H]5,6-epoxide by endogenous 5,6-epoxide. 

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