Juan Castro

Synthesis of Ambrox® from labdanolic acid

Abstract A synthesis of the valuable amber-type odorant Ambrox® from labdanolic acid (main diterpenoid of the acid fraction of non-polar extracts of Cistus ladaniferus L.) is reported. The conversion is based on (a) the α,β-dehydrogenation of methyl labdanolate using an organoselenium reagent, (b) subsequent oxidative degradations of the side chain, and (c) final acid-promoted cyclization of the resulting tetranorlabdan-8α,12-diol. The influence of the temperature and solvent in the cyclization of the diol with p-toluenesulfonic acid is also described. Thus, Ambrox® has been obtained by a six-step procedure in 33% overall yield from methyl labdanolate.

3-Methyl-3-(6,6,6a-trimethyl-hexahydro-cyclopenta[b]furan-2-yl)-butan-2-one

A 40% aqueous solution of sulfuric acid (0.5 mL) was added to a stirred solution of 3,3-dimethyl- 4-hydroxy-5-(2,2,3-trimethyl-3-cyclopentenyl)-pentan-2-one (1) (630 mg, 2.65 mmol) in methanol (5 mL) and the mixture refluxed for 1.5 h.[...]

(Z)-2-Methyl-3-(1-phenyl-ethylamino)-but-2-enoic acid ethyl ester

p-Toluenesulfonic acid (48 mg, 0.25 mmol) was added to a stirred mixture of ethyl 2-methyl-acetoacetate (1) (346 mg, 2.40 mmol) and a-methylbenzylamine (2) (358 mg, 2.95 mmol) in toluene (13 mL) [1].[...]

5-Hydroxy-2-methyl-3-oxo-6-(2,2,3-trimethyl-cyclopent-3-enyl)-hexanoic acid ethyl ester

Sodium (241 mg, 10.48 mmol) was added to absolute ethanol (40 mL) and the mixture refluxed until sodium reacted completely.

endo-N-(5,5-Dimethyl-6-methylene-bicyclo[2.2.1]hept-2-yl)-4-methyl-benzenesulfonamide

p-Toluenesulfonic acid (35 mg, 0.20 mmol) was added to a stirred mixture of campholenic aldehyde (1) (725 mg, 3.81 mmol) and p-toluenesulfonamide (1.22 g, 6.96 mmol) in toluene (20 mL).[...]

(E)-6-(2,2,3-Trimethyl-cyclopent-3-enyl)-hex-4-en-3-one

Ethyl 2-methylacetoacetate (2) (727 mg, 4.53 mmol) was added to a stirred solution of NaH (184 mg, 4.60 mmol) in dioxane (25 mL).[...]

2-(1-Bromo-1-methyl-ethyl)-2-methyl-[1,3]dioxolane

A solution of bromine (0.3 mL, 5.90 mmol) in CCl4 (2 mL) was slowly added over a stirred mixture of 3-methyl-butan-2-one (1) (505 mg, 5.90 mmol) and AcOH (0.33 mL) at room temperature.[...]

8a-Formyloxy-14,15-dinorlabdan-13-one [(-)-4-((1R,2R,4aS,8aS)-2-Formyloxy-2,5,5,8a-tetramethyldecahydro-1-naphthalenyl)-2-butanone]

To a stirred solution of a mixture of E/Z isomers 1 (81 mg, 0.22 mmol, 45:55 ratio) in acetone (5 mL) was added a mixture of KMnO4 (122 mg, 0.77 mmol) and anhydrous MgSO4 (120 mg) at 10 oC [1].[...]

8a,13-Epoxy-14,15-dinorlabd-12-ene (Sclareol Oxide) [(+)-(4aR,6aS,10aS,10bR)-3,4a,7,7,10a-Pentamethyl-4a,5,6,6a,7,8,9,10,10a,10b-decahydro-1H-benzo[f]chromene]

To a stirred solution of a mixture of E/Z isomers 1 (174 mg, 0.52 mmol, 45:55 ratio) in acetone (8 mL) was added a mixture of KMnO4 (260 mg, 1.64 mmol) and anhydrous MgSO4 (230 mg) at 10 oC [1].[...]

Methyl 8-Acetyl-labdanolate (-)-(3S)-5-((1R,2R,4aS,8aS)-2-Acetoxy-2,5,5,8a-tetramethyldecahydro-1-naphthalenyl)-3- methylpentanoic Acid Methyl Ester

Acetic anhydride (0.53 mL, 5.61 mmol) and N,N-dimethylaminopyridine (17 mg, 0.14 mmol) were added to a stirred solution of the alcohol 1 (442 mg, 1.31 mmol) in freshly distilled triethylamine (1.3 mL) [1].[...]