Artemisia alcohol

Except in the case of isobutyraldehyde, where the non-optimized poor yield may be due to the high volatility of the resulting product, the alcohols are formed in good yields. When the aldehyde is sterically hindered (entries 1-2), a-allylation is observed. Conversely, branched alcohols result from unhindered or aromatic aldehydes (entries 4 to 6). Starting from 3-methyl-2-butenal (entry 5), a fluorinated analog of Artemisia alcohol is formed in one step27. 

Artemisia vulgarts L. China Terpinenol-4, (3-caryophyllene, artemisia alcohol, linalool, cineol, camphore, borneol, eucalyptol.33 Reduce or stop menstrual bleeding. Antiasthmatic, antitussive. Treat chronic bronchitis, oral infection, and hypersensitivity. 

Dimethylallyldiisopinocampheylborane, obtained by hydroboration of 3-methylbuta-l, 2-diene with (-)-Ipc2BH, has been used to synthesize the irregular monterpene (+)-artemisia alcohol in 95% e.e. (Figure B5.5). 

Takemoto, T. Nakajima, T. Study on the essential oil of Artemisia annua L. II. Stmcture of /-P-artemisia alcohol, ibid 1310-1313. 

Karamenderes et al. [67] reported the composition and antimicrobial activity of the essential oils obtained from Achillea millefolium L. subsp. pannonica (Scheele) Hayek, Achillea millefolium subsp. millefolium, Achillea arithmifolia Waldst Kitt and Achillea kotschyi Boiss. subsp. kotschyi, four Achillea species from Turkey. 1,8-cineole, Fig. (2), artemisia alcohol and ascaridole were identified as major components. The essential oils showed antibacterial and antifungal effects even with low concentrations. The essential oil of the flowering tops of another Achillea species, Achillea fragantissimum (Forsk.) Sch. Bip growing in Sinai, was analyzed [68]. Santolina alcohol, a- and P-thujone, Fig. (5) and artemisia ketone account for approximately 80% of the oil. The oil showed marked antimicrobial activities against Escherichia coli. Bacillus subtilis and Staphylococcus aureus. 

The efficient addition of allylic bromides to carbonyl compounds in a heated zinc column has been used to synthesize ( )-artemisia alcohol (81 R = H, X = CH2) in 91% yield.Artemisia ketone was synthesized efficiently from 3-methyl-l-trimethylsilylbut-2-ene and 3-methylbut-2-enoyl chloride in the presence of AlCls. Racemic methyl santolinate (82) was synthesized (along with the C-3 epimer ratio 8 1) via Claisen rearrangement, according to Scheme 2 (cf. Vol. 6, p. 7). ... 

New naturally occurring monoterpenes having the artemisia skeleton include artemisia ketone epoxide (208), isolated from Artemisia vulgaris and synthesized from prenyl chloride (15, R = Cl), and senecioic acid (59) chloride under Grignard conditions.( + )-Artemisia alcohol (209) has been isolated from A. herba alba [the usually encountered form is the (- )-(S)-isomer (- )-209]. An incompletely characterized triacetate 210 is also reported from the Brazilian plant Calea oxylepis. ... 

The establishment of natural artemisia alcohol from sage as the (5)-isomer was announced by Zydowsky and Hill in 1982, and an elegant synthesis of both enantiomers by H.C. Brown utilizes the chiral borane 219, which contains a prenyl group. Reaction of the illustrated enantiomer with senecio aldehyde (84) gave the addition product from which (- )-(S)-artemisia alcohol [(- )-209] was obtained after alkaline peroxide oxidation in 96% ee. ... 

Non-Isoprenoid Monoterpenoids.—There has been activity in the field of monoterpenoids formally related to chrysanthemic acid (43) and belonging to the odd artemesyl (44), santolenyl (45), and lavandulyl (46) groups where the customary head-to-tail linkage of isoprene units is not followed. Yomogi alcohol (47), the allylically rearranged artemisia alcohol (51), has been isolated from Artemisia feddei. The santolinyl class now includes two alcohols. 

Grignard-like additions of alkyl halides to carbonyl groups involve exclusive 1,2-addition in the case of a/S-unsaturated aldehydes. The technique is illustrated by an easy synthesis of artemisia alcohol (Scheme 29). ° In two papers, Julia now gives more experimental details of two routes to the artemisia ketone (113). ... 

In cell-free extracts of Artemisia annua and Santolina chamaecyparissus, chrysanthemyl alcohol and its pyrophosphate are incorporated into artemisia ketone and alcohol. Artemisia alcohol (95) is converted into artemisia ketone (94) and tranj-chrysanthemic acid in the preparation from S. chamaecyparissus (Banthorpe et al., 1977a). IPP and DMAPP are incorporated into irregular monoterpenes whereas geranyl and neryl-OPP are not. An enzymatic sulf-hydryl group is involved. 

In a similar trial in Bulgaria, analyzing samples from seven habitats, besides camphorous and 1,8-cineole type individuals, an artemisia alcohol chemotype (with 24%-46% artemisia alcohol in the oil) has been described (Konakchiev and Vitkova, 2004). However, in this examination, the populations could not be characterized, and the abundance of the three chemotypes has not been described either, as only a single individual has been sampled from each habitat Therefore, the... 

WiLLHALM, B., and A. F. Thomas Synthesis and Structure of Yomogi Alcohol, and Alcohol Related to Artemisia Alcohol. Chem. Commun. 1969, 1380. 

It is of interest to note that artemisia alcohol (18) produced in the hydrolysis of 16-OPy I" is essentially completely racemic (>98%) (57). Apparently (18) is formed by nucleophilic capture of the acyclic allylic carbonium ion (29) rather than direct attack in the 3 position of the chrysanthemyl carbonium ion (28). Nucleophilic substitution upon cyclopropylcarbinyl cations to give homoallyl products occurs with inversion of configuration 74—75). In the case of (28), however, position 3 is highly hindered by the adjacent gem dimethyl groups thus collapse to the allylicly stabilized (29) is faster than direct substitution. The formation of a small amount of cw-chrysanthemol (27, 0.25%) is taken to indicate that allylic ion (29) recyclizes, at least in part, back to (28) and its cis isomer (30). 

If the S configuration tentatively assigned to the carbinol carbon in natural artemisia alcohol (18) (55) is sustained, it would indicate that in the actual biosynthesis the nucleophilic substitution occurs with net retention of configuration. Since a direct substitution upon a cyclopropylcarbinyl ion should occur with inversion rather than retention 74—75), ring opening to the free allylic cation followed by stereospecific capture is proposed (55). 

---