Synthesis 2005(6): 1019-1027  
DOI: 10.1055/s-2005-861863
FEATUREARTICLE
© Georg Thieme Verlag Stuttgart · New York

An Effective Method for the Synthesis of 13C-Labeled Polyprenylhydroxy­benzoic Acids

Martin Lang, Wolfgang Steglich*
Department Chemie, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13 (F), 81377 München, Germany
Fax: +49(89)218077756; e-Mail: [email protected];
Further Information

Publication History

Received 12 January 2005
Publication Date:
09 March 2005 (online)

Abstract

The synthesis of side-chain 13C-labeled geranylgeranyl-4-hydroxybenzoic acids and geranylgeranyl-3,4-dihydroxybenzoic acids is described. The synthesis starts from O-protected methyl hydroxyiodobenzoates, which are transformed into Grignard reagents by low-temperature iodine-magnesium exchange according to Knochel’s procedure. Copper catalyzed cross-coupling with labeled geranylgeranyl bromide followed by deprotection affords the products with good yields and full retention of stereochemistry.

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1

New address: M. Lang, 4SC AG, Am Klopferspitz 19a, 82152 Martinsried, Germany.

28

On addition of MeOH, work-up and flash chromatography, the corresponding dehalogenated compounds were isolated in nearly quantitative yields.

34

HCl was generated by alcoholysis of AcCl in i-PrOH.

40

Methyl 4-hydroxy-3,5-diiodobenzoate was separated from 1 by flash chromatography. Non-iodinated material could be removed neither from 1 nor from 2. Thus, a mixture of 2 and methyl 4-(methoxymethoxy)benzoate was employed in the cross coupling reactions.

42

Impurity: 2-iodo-4,5-bis(methoxymethoxy)benzaldehyde.

45

IR data of the corresponding unlabeled compound.