Clerodane Diterpenoids

Tokoroyama T. Synthesis of Clerodane Diterpenoids and Related Compounds -Stereoselective Construction of the DecaUn Skeleton With Multiple Contiguous Stereogenic Centers Synthesis 2000 611-633... 

Januario AH, Simone LS, Silvana M, et al. Neo-clerodane diterpenoid, a new metallo-protease snake venom inhibitor from Baccharis trimera (Asteraceae) anti-proteolytic and anti-hemorrhagic properties. Chem Biol Interact 2002 150 243-251. 

A SN reaction-based domino route to clerodane diterpenoid tanabalin (2-488) [258] has been described by Watanabe s group (Scheme 2.111) [259]. This natural product is interesting as it exhibits potent insect antifeedant activity against the pink bollworm, Pectinophora gossypiella, a severe pest of the cotton plant The domino sequence towards the substituted trans-decalin 2-487 as the key scaffold is induced by an intermolecular alkylation of the (5-ke toes ter 2-484 with the iodoalkane 2-483 followed by an intramolecular Michael addition/aldol condensation (Robin-... 

Bicyclic diterpenes-clerodanes. An important group of Insect antifeedants are the clerodane diterpenoids, which have been isolated from several different plant families (13)(Figure 1). Particularly well studied are the antifeedant activities of caryoptln and clerodin, and their derivatives, from Clerodendron and Caryopteris, Verbenaceae, against the tobacco cutworm Spodoptera litura L. (25-27). 

Belles al. have recently discussed the structure-activity relationships of several natural clerodane diterpenoids and their derivatives, and have compared their activity with that of some synthetic butenollde derivatives (34). 

Esquivel, G., Calderon, J.S., and Elores, E., A neo-clerodane diterpenoid from Scutellaria seleri-ana, Phytochemistry, 47, 135, 1998. 

METHODOLOGY VALIDATION AND STRUCTURE CORRECTION BY TOTAL SYNTHESIS THE CASE OF THE CLERODANE DITERPENOID, SACACARIN... 

Bruno M, Fazio C, Piozzi F, Savona G, Rodriguez B, de la Torre MC (1995) Aeo-Clerodane Diterpenoids from Teucrium racemosum. Phytochemistry 40 505... 

Beauchamp PS, Bottini AT, Caselles MC, Dev V, Hope H, Larter M, Lee G, Mathela CS, Melkani AB, Millar PD, Miyatake M, Pant AK, Raffel RJ, Sharma VK, Wyatt D (1996) Aeo-Clerodane Diterpenoids from Ajuga parviflora. Phytochemistry 43 827... 

E-isolinaridial and E-isolinaridial methylketone are two neo-clerodane diterpenoids isolated from the aerial parts of Linaria saxatilis var. glutinosa (Schrophulariaceae). Benrezzouk et al. evaluated these compounds on multiple inflammation pathways and found that they were not COX-1/COX-2 inhibitors [139]. However, E-isolinaridial and E-isolinaridial methylketone were dual inhibitors against purified phospholipase A2 and 5-lipoxygenase. E-isolinaridial and E-isolinaridial methylketone showed potent inhibition of cell-free 5-LOX enzyme with IC50 values of 0.42 pM and 1.41 pM,... 

Clerodanes.—The X-ray structure determination of the cis -clerodane (16) has been reported.24 This confirms the stereochemistry of a number of Solidago diterpenoids which have been correlated with this lactone. Linaridial (17), an unstable cis-clerodane dialdehyde, has been isolated25 from Linaria japonica (Scrophulariaceae). A number of clerodane diterpenoids have been isolated26 from Stachys annua (Labiatae), including annuanone (18) and the corresponding saturated ketone and... 

In the area of natural product characterization, Wall and colleagues utilized 3 mm NMR probe capabilities in the characterization of novel bioactive clerodane diterpenoids from the leaves and twigs of Casearia sylvestris.149 The general structure of the three new clerodanes is shown by 72, the molecules differing in the length and branching of the alkyl side-chain substituent. 

Casearia sylvestris Sw. - cha-de-frade Insomnia Leaf (decoction, ingested) Quilombolas Terpenes [333] essential oil [334,335] diterpene [336] clerodane diterpenoids [337,338] Antiuleer activity [354] abortive activity [338]... 

The naturally occurring clerodane diterpenoid ( )-sacacarin has been synthesized by R.B. Grossman and co-workers in only 10 steps using a double annulation of a tethered diacid and 3-butyn-2-one. " The second ring of sacacarin was prepared by an intramoiecuiar Dieckmann condensation of an ester and a methyl ketone in excellent yield. The resulting end was then immediately converted to the corresponding ethyl enol ether using ethanol and an acid catalyst. 

Grossman, R. B., Rasne, R. M. Short Total Syntheses of Both the Putative and Actual Structures of the Clerodane Diterpenoid ( )-Sacacarin by Double Annulation. Org. Lett. 2001, 3, 4027 030. 

Tokoroyama T (2000) Synthesis of clerodane diterpenoids and related compounds - stereoselective construction of the decalin skeleton with multiple contiguous stereogenic centers. Synthesis 611-633... 

Bruno M, Fazio C, Arnold NA (1996) Neo-clerodane diterpenoids from Scutellaria cypria. Phytochemistry 42 555-557... 

Efremov, L, and Paquette, L.A., First synthesis of a rearranged ec>-clerodane diterpenoid. Development of totally regioselective trisubstituted furan ring assembly and medium-ring alkylation tactics for efficient access to (—)-teubrevin G, J. Am. Chem. Soc., 122, 9324, 2000. 

For the synthesis of clerodane diterpenoids, Tokoroyama and co-workers examined another version of the intramolecular Hosomi-Sakurai reaction (108). Substrates 55.1 and 55.4 were cyclized to yield adducts 55.2-55.3 and 55.5-55.6, respectively (Scheme 55). 

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