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Synthesis of deuterium labeled perillyl alcohol and dual C‐13 and deuterium labeled perillic acid, major metabolites of d‐limonene
Author(s) -
Chen Haitao,
Chan Kenneth K.
Publication year - 1997
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(199705)39:5<369::aid-jlcr983>3.0.co;2-f
Subject(s) - chemistry , cyclohexene , aldehyde , deuterium , wittig reaction , ethylene glycol , ethylene , alcohol , organic chemistry , ketone , double bond , yield (engineering) , medicinal chemistry , catalysis , quantum mechanics , metallurgy , physics , materials science
Dual C‐13 and deuterium labeled perillic acid, [(1,1‐dideuterio‐1‐ 13 C‐2‐methyl)ethenyl]‐1‐cyclohexene‐1‐carboxylic acid ( 6 ) and deuterated perillyl alcohol, [(2,2‐dideuterio‐1‐methyl)ethenyl]‐1‐deuteriohydroxymethyl‐1‐cyclo‐hexene ( 9 ) were synthesized from commercially available (4S)‐(‐)‐perillaldehyde ( 1 ). Compound 1 was first protected with ethylene glycol to yield the ethylene ketal followed by oxidation with OsO 4 /NalO 4 to cleave the terminal double bond to afford the key intermediate ketone, 4‐acetyl‐1‐cyclohexene‐1‐carboxaldehyde ethylene ketal ( 3 ). 3 was then converted to the labeled perillyl aldehyde by Wittig reaction with prepared Ph 3 P 13 CD 3 l or Ph 3 PCD 3 l followed by deprotection to give the labeled perillaldehydes, [(2,2‐dideuterio‐2‐ 13 C‐1‐methyl)ethenyl]‐1‐cyclohexene‐1‐carboxaldehyde ( 5 ) or [(2,2‐dideuterio‐1‐methyl)ethenyl]‐1‐cyclohexene‐1‐carboxaldehyde ( 8 ). 5 was further oxidized by freshly prepared Ag 2 O to give the desired compound 6 . 8 was reduced by LiAlD 4 to afford the desired compound 9 . The same synthetic procedure may be adopted to synthesize the radioactive isotope labeled perillic acid and perillyl alcohol. © 1997 John Wiley & Sons, Ltd.