Retinoid chemistry

These established facts made that retinoid chemistry of today, more than ever, a challenge for chemists. 

This account, relative to retinoid chemistry, was in ad equation and corroborated the older methodologies of retinoid syntheses, which favored the C(H)-C(i2) way. Significantly, since 1990, more than forty references have linked p-iony 1 ideneacetaldehyde as an intermediate in the syntheses of retinoids (ref CAS, Sci. Finder). This choice could be... 

Al-Badri, H., About-Jaudet. E.. and Collignon, N., New and efficient synthesis of ( )-4-diethoxyphos-phonyl-2-methyl-2-butenal and of ethyl ( )-4-diethoxyphosphonyl-2-methyl-2-butenoate, important building blocks in retinoid chemistry. Tetrahedron Lett., 36, 393, 1995. 

A coupling reaction long used in acetylene chemistry is the Cadiot-Chodkiewicz coupling [112] its use in retinoid synthesis is demonstrated by the transformations depicted in Scheme 2-19 [113], The enyne precursor 169, on Cadiot-Chodkiewicz coupling with 3-bromo-2-propyn-l-ol (170) yields the diyne 171 which, by methodology long established in retinoid chemistry [114], may either be chain-elongated to dehydroretinal 172 or — via the diynal 173 — to the bis-acetylenic retinal 174. 

In the course of almost 50 years of synthetic retinoid chemistry up to the present time, a large number of processes for the synthesis of retinol (1) and its esters, such as retinyl acetate (9) and retinyl palmitate (113), have been developed. The most important large-scale industrial processes today are based on the work of Isler et al. at Hoffmann-La Roche, and of Pommer et al. at BASF. These two processes probably satisfy a large part of the world demand for retinol (1) (vitamin A), most of which is used for the production of animal feeds. 

The synthesis of retinoids by sulfonylalkylation has the advantage that the auxiliary substance in the (C15 + C5) linking, i.e., the sulfinic acid derivative, is obtained in the elimination step in a form such that it can be directly used for a further synthesis cycle. In contrast, the triphenylphosphine oxide formed in Wittig reactions first has to be reduced again to triphenylphosphine. However, the range of application of the sulfinate method in retinoid chemistry is still to be established, as has been done for the Wittig reaction in the past 30 years. 

The synthesis of retinoidal benzoic acid and naphthoic acid derivatives has opened the door to the development of an entirely new retinoid chemistry. Although classical chemical properties of retinoids, such as polyene structure, light sensitivity, and cis-trans isomerism of the side chain, are diminished or absent in these new compounds, they are clearly retinoids. X-ray crystallography has shown that the critical molecular dimensions of biologically active forms are almost identical to those of all-rra/2.y-retinoic acid (Strickland et al., 1983). 

The Retinoids Biology, Chemistry and Medicine, Raven Press,... 

N. Krause, in Chemistry and Biology of Synthetic Retinoids, M. I. Dawson,... 

The central cleavage of P-carotene 1 is most likely the major pathway by which mammals produce the required retinoids il), in particular, retinal 2, which is essential for vision and is subsequently oxidized to retinoic acid 3 and reduced to retinol 4. An alternative excentric cleavage of 1 has been reported involving scission of the double bond at C7-C8 producing P-8 -apocarotenal 5 (2a,2b) which is subsequently oxidized to 2 (Fig. 1) (2c). The significance of carotene metabolites such as 2, 3 and 4 to embryonic development and other vital processes such as skin and membrane protection is a major concern of medicinal chemistry. 

HongWK, ItriLM (1994) Retinoids and Human Cancer. In Sporn MB, Roberts AB, Goodman DS (eds). The Retinolds Blology, Chemistry, and Medicine, 2nd ed Raven Press, New York, p 597... 

Retinoid acid is a transcription factor. Retinoids play significant roles in dermatology, in the prevention of some cancers, and in the chemistry of vision. Consequently, many works have been dedicated to fluorinated analogues of retinoids. 

Further sulfoxide elimination led to the formation of dienoate esters, including a novel retinoid analogue (Eq. 93) [271]. More recent chemistry involved 1,2-Stevens rearrangement to gain access to aminoacid analogues (Eq. 94) [272]. The second strategic use involves the addition of alcohols to the... 

Freebern, W.J., Osman, A., Niles, E.G., Christen, L. and LoVerde, P.T. (1999a) Identification of a cDNA encoding a retinoid X receptor homologue from Schistosoma mansoni. Evidence for a role in female-specific gene expression, journal of Biological Chemistry 274, 4577 t585. 

Gale JB (1993) Recent advances in the chemistry and biology of retinoids. Prog Med Chem 30, 1-55. 

Retinoid-A term undergoing nearly continual modification in order to accurately describe the characteristics of a large family derived from the carotenes and xanthophylls. The family exhibits specific properties required in vision, metabolism and reproduction. Many of these properties are dependent on the stereo-chemistry of the materials. Only some of the stereo-chemical features may be required in a given application. The definition of Spom, et. al. in 1994 is the most widely used. However, it does not stress the visual properties required to form a chromophore in vision. 

Goodwin has provided a useful summary of the structural chemistry applicable to the retinoids of vision36. However, the book is not as comprehensive as needed to address all of the types of Vitamin A. He also refers to a separate essay on the structural notation he uses37. Taylor Ikawa have provided additional nomenclature, more semisystematic names and excellent information on laboratory evaluation techniques38. 

Stereo-chemistry has played a large role in attempting to understand the visual process. While its role in the actual chromophores of vision appears to be negligible, the stereochemistry of other retinoids is widely discussed. However, many different systems of notation have been used over the years. Goodwin provides a broad review of this terminology39. 

Dawson, M. Okamura, W. (1990) Chemistry and Biology of Synthetic Retinoids Boca Raton FI CRC Press fig. 2. 

Frickel225 has provided a comprehensive review of the chemistry of the retinoids which shows that most of the literature relates to molecular modifications aimed at pharmaceutical purposes. It has been rare to find a retinoid designed to include a polar element at a side chain location, although some work has been done on substituting fluorine into the side chain. Dawson Hobbs226 updated Frickel s review to 1994 and noted some additional work... 

Much of the new chemistry on the coupling of alkynyl halides has dealt mostly with applications of known methods. The Cadiot-Chodkiewicz-type coupling reactions (i.e. terminal acetylene coupling with alkynyl halides) have formed the cornerstone of synthesis of acetylenic retinoids (i.e. 9)58. 

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