Terpenes. XIX.¹ Synthesis of Patchouli Alcohol²

Abstract

protons, confirming its total reduction. Chromatography on alumina still did not permit crystallization, so the material was acetylated with pyridine and acetic anhydride. Prisms of racemic 0,N-diacetyldemethyldihydrogalanthamine were obtained which were recrystallized from ethyl acetate and sublimed at 150" (0.1 mm.), m.p. 208-209.5", [ o l I z 3~ 0.00,' [alZ3436 0.00' ( c 0.19, chloroform). The infrared spectrum in chloroform was identical with its optically active counterpart (m.p. 177-179'). Surprisingly, the compound does not appear t o depress the racemic 0,s-diacetyldemethylgalanthamine, m.p. 204-205', b u t fortunately its infrared spectrum ( K B r ) exhibits many points of difference.Conversion of Dihydronarcissamine to Racemic Dihydrogalanthamine.--4 solution of 150 mg. of the crude hydrogenation product of narcissamine in a mixture of 1 ml. of 9076 formic acid and 1 ml. of 3 i y G formalin was heated on the steam bath for 3 hr., basified, and extracted into chloroform. The product was then chromatographed over alumina with 1 YG ethanol in ethyl acetate and the resulting oil evaporatively distilled a t 150' (0.1 m m i . The infrared spectrum of the product is identical in chloroform solution with ( -)-dihydrogalanthamine and gas phase chromatography shows a retention time identical with the latter (see above). The material was purified by crystallizing its hydriodide salt from water, recovering the free base with alkali, and evaporatively distilling the product. Still an oil, the product showed [ a I z 3 D 0.0", [olIz3496 0.0" ( c 0.655, chloroform).Anal. Calcd. for C l i H~N 0 3 : C , 70.56; H , 8.01. Found: C, 70.32; H, 7.91.The compound formed a methiodide from acetone which was recrystallized from ethanol-water; m.p. 300' dec. The infrared spectrum ( K B r ) of the salt is very similar to, but not identical with, t h a t of ( -)-dihydrogalanthamine methiodide.(+)-Camphor was converted to (-))-homocamphor by known methods and in a short synthetic sequence the latter was transformed to the tricyclic cyclopentenone 10. Condensation with methylmagnesium iodide or with triphenylphosphinemethylene followed by hydrogenation yielded 8-patchoulene ( 12). Rearrangement of the corresponding epoxide 16 with boron fluoride furnished the desired unsaturated alcohol 18. This key intermediate was subsequently transformed to patchoulione ( 2 ) and to a-patchoulene (23). ' % previously accomplished b u t at t h a t time incorrectly interpreted reconversion of ol-patchoulene (23) to patchouli alcohol ( 2 8 ) completed the synthesis. Some transformations of the natural product 28 are reinterpreted in terms of a new structure determined by the X-ray method.

Characterisation of a Recombinant Patchoulol Synthase Variant for Biocatalytic Production of Terpenes

“…Assuming a standard Michaelis-Menten kinetic, the PTS var. 1 has K M = 8.0 ± 6.5 μM and v max = 6.93 ± 1.33 μM min 1 . Accordingly to that, enzyme activity was calculated to be k cat = 0.072 s 1 and K cat /K M = 9000.0 s 1 mol −1…”

“…Eluent A was the lysis buffer, eluent B was lysis buffer supplemented with 500 mM of imidazole and flow rate was 3 mL min 1 .…”

“…Two microlitres of sample were injected via autosampler (splitless mode, injector temperature 240°C). Temperature gradient was as follows: 40°C held for 20 s, raised to 210°C (10°C min 1 ), held for 1 min, raised to 230°C (40°C min 1 ) and held for 3 min. The FID was heated to 300°C.…”

“…Today, patchouli oil is mainly produced from the plant raw materials by steam distillation. Usually, it contains 30-50 % of the commercially relevant terpene alcohol patchoulol which embodies the main contributor to the typical patchouli scent [1].…”

Stereoselective synthesis of α-bulnesene, 4-epi-α-bulnesene, and 5-epi-α-bulnesene

“…Elution with 200 ml benzene afforded (doublet, 3H, -C13H3, J11,13 = 7 HZ). The chemical shifts assigned to C3H and -C14H3 were confirmed by frequency-swept decoupling experiments in which the proton at C-3 was strongly irradiated, thus eliminating the allylic coupling between C3H and -C14H3, and causing the signals at 7 (10.5 g) in 6~, secondary methyls, J = 6.9 Hz, 6.8 Hz, respectively). 400 ml of anhydrous methanol at 0" was added sodium ~h , instability of this c o m p o u n~ precluded the borohydride (6 g).…”