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Optimization and synthesis of ( E )‐4‐[2‐(3,4‐dihydro‐4,4‐dimethyl‐2 H ‐1‐benzopyran‐6‐y1)‐1‐propenyl]benzoic acid‐11‐[ 14 C]
Author(s) -
Liu Shengquan,
Berlin K. Darrell,
SimmsKelley Melissa D.,
Nelson Eldon C.,
Benbrook Doris M.
Publication year - 1999
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/(sici)1099-1344(199908)42:8<789::aid-jlcr239>3.0.co;2-#
Subject(s) - chemistry , propenyl , benzopyran , benzoic acid , stereochemistry , organic chemistry
Heteroarotinoids may be useful in the treatment of skin disorders and a wide variety of cancers. A synthesis of the C‐14 labelled heteroarotinoid, ( E )‐4‐[2‐(3,4‐dihydro‐4,4‐dimethyl‐2 H ‐1‐benzopyran‐6‐y1)‐1‐propenyl]benzoic acid‐11‐[ 14 C] (* 1 ) is described via a multistep procedure similar to that used to obtain the unlabelled compound 2 . The latter has shown good activity in several assays compared to the standard trans ‐retinoic acid ( 3 ). Reduction of the carbonyl group in 4,4‐dimethylchroman‐6‐y1 methyl ketone‐(carbonyl‐ 14 C) (* 5 ) with LiA1H 4 gave alcohol * 6 . Phosphorylation with triphenyl‐phospine hydrobromide in methanol led to the corresponding phosphonium salt * 7 . Addition of n ‐butyllithium to * 7 in ether at −78°C generated the Wittig reagent in situ and to this was added ethyl 4‐formylbenzoate. Workup and chromatography afforded E ‐ester * 8 and Z ‐ester * 9 which were both hydrolyzed to labelled * 1 . Labelled * 1 was identical to unlabelled 2 in terms of spectral data and melting point. The specific activity of * 1 was determined to be 57.2 μCi/mg. Copyright © 1999 John Wiley & Sons, Ltd.