An expedient route to a versatile intermediate for the stereoselective synthesis of all-trans-retinoic Acid and beta-carotene

Babler, James H.; Schlidt, Scott A.

doi:10.1016/0040-4039(93)88020-j

Cited by 12 publications

(5 citation statements)

References 9 publications

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“…The HWE reaction was adapted at BASF for the preparation of all -trans -retinoic acid ( 3 ) by the C 15 + C 5 condensation scheme using 17 and 236 followed by the saponification of ethyl all- trans -retinoate ( 237 ) (Scheme ) . Allylphosphonate 239 , obtained by the isomerization of vinylphosphonate 238 induced by t -BuOK in DMSO, can be alternatively condensed with aldehyde 149 to stereoselectively yield 237 …”

Section: Synthesis Of Retinoidsmentioning

confidence: 99%

Functions, Therapeutic Applications, and Synthesis of Retinoids and Carotenoids

et al. 2013

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Section: Synthesis Of Retinoidsmentioning

confidence: 99%

Functions, Therapeutic Applications, and Synthesis of Retinoids and Carotenoids

et al. 2013

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“…A gram-scale cross-metathesis reaction between 10 and (2E,4E/Z)-3-methylhexa-2,4-dienoate (11) afforded retinoate in 68% yield with excellent stereoselectivity (Scheme 5B-2), and retinoate (1.12 g) could be easily reduced to vitamin A (Scheme 5B-3) or hydrolyzed to afford retinoic acid (Scheme 5B-4) in 87% and 90% yields, respectively. In contrast, the known method for vitamin A and its derivatives required 5 linear steps in 43% yield 14 or 9 linear steps in 40% yield 15 from β-lonone using equivalent hardly available zirconium reagent, respectively. Subsequently, we used the vinylzincation method to synthesize the natural product nakienone A, a conjugated polyene that displays cytotoxicity and antibacterial activity (Scheme 5C).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Iron-Catalyzed Vinylzincation of Terminal Alkynes

Huang

Sun

et al. 2021

J. Am. Chem. Soc.

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Organozinc reagents are among the most commonly used organometallic reagents in modern synthetic chemistry, and multifunctionalized organozinc reagents can be synthesized from structurally simple, readily available ones by means of alkyne carbozincation. However, this method suffers from poor tolerance for terminal alkynes, and transformation of the newly introduced organic groups is difficult, which limits its applications. Herein, we report a method for vinylzincation of terminal alkynes catalyzed by newly developed iron catalysts bearing 1,10-phenanthroline-imine ligands. This method provides efficient access to novel organozinc reagents with a diverse array of structures and functional groups from readily available vinylzinc reagents and terminal alkynes. The method features excellent functional group tolerance (tolerated functional groups include amino, amide, cyano, ester, hydroxyl, sulfonyl, acetal, phosphono, pyridyl), a good substrate scope (suitable terminal alkynes include aryl, alkenyl, and alkyl acetylenes bearing various functional groups), and high chemoselectivity, regioselectivity, and stereoselectivity. The method could significantly improve the synthetic efficiency of various important bioactive molecules, including vitamin A. Mechanistic studies indicate that the new iron-1,10-phenanthroline-imine catalysts developed in this study have an extremely crowded reaction pocket, which promotes efficient transfer of the vinyl group to the alkynes, disfavors substitution reactions between the zinc reagent and the terminal C−H bond of the alkynes, and prevents the further reactions of the products. Our findings show that iron catalysts can be superior to other metal catalysts in terms of activity, chemoselectivity, regioselectivity, and stereoselectivity when suitable ligands are used.

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“…This approach was not a new idea; the key C 15 -phosphonate intermediate 84 had been already described in the 1960s . In the early 1990s, James Babler started to develop this strategy mainly to avoid some difficulties existing in the C 15 + C 5 Wittig strategy such as the separation of triphenylphosphine oxide from the retinoid product . The idea was to start from C 14 -aldehyde 18 , which was later optimized by Takeda Chemical Industries Ltd. to the C 14 -aldehyde 17 as in the DSM-Firmenich/Roche route since it was more easily industrially accessible.…”

Section: Recent Entrants Into Vitamin a Productionmentioning

confidence: 99%

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

Bonrath,

Gao,

Houston

et al. 2023

Org. Process Res. Dev.

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In 1948, the first kilograms of synthetic vitamin A (acetate) were produced by F. Hoffmann-La Roche, eliminating the need to extract this vital compound from natural sources; this year marks 75 years of successful production. Since then, a number of chemical routes have been commercialized. Of these, three processes have stood the test of time and are still in use today, with only minor modifications. This review covers both the historical and scientific developments in the production of vitamin A derivatives from their beginnings up until recent developments including a fully catalytic process and the successful pilot-scale production via fermentation. In addition, the development of formulation technologies, which have gone hand-in-hand with chemical process development, is described; correct formulation is essential for stabilizing vitamin A derivatives which are sensitive to light and oxidation.

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An expedient route to a versatile intermediate for the stereoselective synthesis of all-trans-retinoic Acid and beta-carotene

Cited by 12 publications

References 9 publications

Functions, Therapeutic Applications, and Synthesis of Retinoids and Carotenoids

Functions, Therapeutic Applications, and Synthesis of Retinoids and Carotenoids

Iron-Catalyzed Vinylzincation of Terminal Alkynes

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

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