Anti-inflammatory activity total synthesis

Finally, Maikov and coworkers used terpene-derived IV,IV -dioxide 21.22 in a total synthesis of marine serrulatane diterpene (—)-elisabethadione 21.67 (Scheme 21.9) exhibiting potent anti-inflammatory activity. Asymmetric crotylation of cinnamaldehyde 21.65 on a 5 mmol scale afforded syn-homoallylic alcohol 21.66 in 82% yield, 94% enantiomeric excess and with complete distereoselectivity. Other key reactions to install the stereogenic centres of the target molecule included anionic ory-Cope rearrangement and cationic cyclisation. ... 

Hydroesterification of the C—C triple bond of a macrocycle has been used as the key step for the total synthesis of several members of the pseudopterane family possessing significant biological activity such as cytotoxicity or anti-inflammatory activity [45]. As any attempts to convert propargylic alcohol 31 directly into butenolide 34 by conventional methods failed, a new route was developed via atmospheric alkoxycarbonylation of mesylate 32 to allenic ester 33. 

The Julia-Lythgoe olefination and Kocienski modification have applied broadly in the synthesis of nature products. Isoprostane of A2 and h are isomeric of the cyclopentenone prostaglandins A2 and J2, respectively, which are reported to exert unique biological effects. Prostaglandins of A2 and J2 series have been reported to be active against a wide variety of DNA and RNA viruses, including HIV-1 and influenza virus. They also possess a potent anti-inflammatory activity due to the inhibition and modification of the subunit IKKP of the enzyme IA B kinase. Zanoni and co-workers reported the first total synthesis of A2 Isoprostane 101 employed a stereoselective Julia-Lythgoe olefination in the formation of C 13 14 double bond. The intermediate 99, obtained in 87% yield by addition of sulfone 97 to aldehyde 98, was reduced by Na(Hg) to alkene 100 in 81% yield. 

The biological activity displayed by the perhydroazulenes, ranging from diuretic and anti-inflammatory to antitumor, combined with the unique bicyclo [6-3-0] system make them very attractive synthetic targets. The approach of Trost and Higushi to this class of compounds, exemplified by the total synthesis of isoclavu-kerin 65 (Scheme 12.12) [34], has the distinctive feature that it allows the simultaneous formation of both the five- and seven-membered rings through a palladium-catalyzed formal [3+2] cyclization as its key step [35]. 

A number of dimeric carbazole alkaloids have been isolated from various natural sources in recent years, which have been found to exhibit various biological activities including antitumor, anti-inflammatory, and cytotoxic activities. In 1996, clausenamine A was isolated from the stem and root bark of Clausena excavata, which is used in Chinese herbal medicine for detoxification treatment following poisonous snakebites. The first total synthesis of clau-... 

Historical At the beginning of the 1930 s U. S. von Euler and M. W. Goldblatt independently detected a substance with activity in smooth musculature in seminal fluid, the structure of this compound was elucidated by Beigstrdm in 1958-1964. Further key data 1968 total synthesis by Corey, beginning of the 1970 s elucidation of the mechanism of action of nsaid (nonsteroidal anti-inflammatory drugs), 1975 thromboxane, 1976 prostacyclin, 1979 leukotrienes, 1982 Nobel Prize for Medicine awarded to Vane, Samuelsson, and Bergstrom. ... 

The same authors have reported another extension of this methodology applied to the development of the first total synthesis of the naturally occurring and biologically active product, (-l-)-frondosin A [41]. This product is known to inhibit the binding of interleukin-8, a chemokine that has been implicated in a wide range of acute and chronic inflammatory disorders, including psoriasis and rheumatoid arthritis. Moreover, it has been shown to exhibit anti-HIV activity. As shown in Scheme 20.22, the key step of this... 

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