Ingenol derivatives

Ingenol derivatives Ingenol derivatives may inhibit virus absorption at least in part through downregulation of CD4 molecules on the host cells. 

Sulfated polysaccharides Ingenol derivatives Flavonoids Glycyrrhizin... 

Although ingenol derivatives are highly potent inhibitors of HIV-1 replication in acutely infected cells, it was recently shown that some ingenol derivatives enhance HIV-1 replication in chronically infected cells, whether or not through activation of the nuclear factor kB (NF-kB) and protein kinase C (PKC). 

Ingenol derivatives are restricted to several species of the genus Euphorbia. These compounds exhibit toxicological and cocarcinogenic properties similar to those of the phorbol compounds. 

Ingenol derivatives, including kansuiphorins A, B, C, and D are found (83, 84). Kansuiphorin A had in vitro IC50 values ranging from 0.03-0.33 pg/mL against various leukemia, melanoma, and non-small cell lung, colon, and renal cancer cell lines, and kansuiphorins A and B were potent against P-388 leukemia in mice with T/C values of >176 and 177% at 0.1 and 0.5 mg/kg, respectively (83). 

Cyclic carbonic esters were also prepared, for example, from the cardiac glycoside proscillaridine[257] (where besides CDI the benzyloxycarbonylimidazole was successfully used), ingenol, 2581 the macrolide antibiotic tylosine,[259] and an erythromycin A derivative.12601... 

Additions to Cyclohexenones and Related Systems. Irradiation of the diox-enone derivative (29) in acetonitrile-acetone at 0°C affords the adduct (30) in 60% yield. This compound was a key intermediate in the first total synthesis of racemic ingenol. A further study has shown that the enone (31) also undergoes cycloaddition on irradiation under the same conditions. This yields the adduct... 

The ingenol diterpenes are very important synthetic targets, due to their impressive structures and biological activities, reinforced by the recent drug approval of Picato (ingenolmebutate) gel for treatment of actinic keratoses. The synthesis shown in Scheme 23 requires the RCM to close the central seven-membered ring, on the way to an oxyingenol derivative [58]. 

Photocycloaddition of the allylic chloride 246 proceeds in 60% yield to give the desired photoadduct 247. Fragmentation of 247 with methanolic potassium carbonate generates ester 248. Reduction of the ester with lithium aluminium hydride, elimination of the chloride with DBU, and silylation of the primiary alcohol with tert-butyldimethylsilyl chloride (TBSCl), give 249 as a 7 1 mixture of the C-6 a [3 epimers in 35% yield from 247. Ingenol is derived from 247 in a 24-step sequence. 

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