Aplysin

Provided that the silanolate elimination proceeds with anti selectivity, it must be concluded, that the intermediate homoallylic alcohol has an anti configuration, and thus the reagent has an ( -configuration. Acidic hydrolysis of the enol ether leads to enones the overall sequence consists of a nucleophilic acroylation. This has also been applied in the total synthesis of the marine diterpene ( )-aplysin-2067. 

Aplysin has marked effects in mammalian tissue and produces hypotension, bradycardia, neuromuscular paralysis, and contracture of intestinal smooth muscle (85). Aplysiatoxin causes an elevation in blood pressure resistant to adrenoceptor blockade (86). 

Hong and coworkers have investigated the cycloaddition chemistry of fulvenes with a wide variety of alkenes and alkynes in great detail [191]. As one example, the reaction of 6,6-dimethylfulvene with benzoquinone is shown in Scheme 6.92. Under microwave conditions in dimethyl sulfoxide (DMSO) at 120 °C, an unusual hetero-[2+3] adduct was formed in 60% yield, the structure of which was determined by X-ray crystallography. The adduct is a structural analogue of the natural products aplysin and pannellin and differs completely from the reported thermal (benzene, 80 °C) Diels-Alder cycloaddition product of the fulvene and benzoquinone (Scheme 6.92) [191]. 

Laronze and colleagues used a similar procedure to built the dihydrofuran ring of the marine sesquiterpene Aplysin (123). 

A study of Laurencia tristicha from the South China Sea has discovered the hydroxylated aplysins, 10-hydroxyepiaplysin (406) and 10-hydroxyaplysin (407) (602), and 4-bromo-l,l-epoxylaur-ll-ene (408), which was previously synthesized but not found naturally (603). Laurencia microcladia from the North Aegean Sea has yielded the new 409 and 410, which exhibit significant cytotoxicity against two lung cancer cell lines (604). This red alga also contains the dimeric cyclolaurane 411 (595). An East China Sea collection of Laurencia okamurai has led to the isolation of the novel laureperoxide (412) and 10-bromoisoaplysin (413)... 

Harrowven DC, Lucas MC, Howes PD (2001) The Synthesis of a Natural Product Family From Debromoisolaurinterol to the Aplysins. Tetrahedron 57 791... 

This three-carbon homologation was used in a synthesis of the diterpene (— )-aplysin-20 (4) from nerolidol (equation 1). ... 

A subsequent analysis of specimens of A. kurodai collected in 1985 from the Mei Prefecture in Japan yielded a new labdane-type diterpene, cpi-aplysin-20 [21], which is a diastereomer of aplysin-20 [2 2](36), together with the enantiomer of isoconcinndiol [2 3](37). 

Ethyl diazoacetate has been used extensively in the homologation of ketones to 3-keto esters. Lewis acid is required for the reaction (equation 23). ° There is a tendency for the least-substituted group to migrate, particularly if one group is fully substituted (equation 24). In a total synthesis of ( )-aplysin (20) this selective rearrangement was applied (Scheme 9), and a similar approach was used in a synthesis of (+)-hirsutic acid. Ethyl diazoacetate has also been used in the homologation of acyclic... 

Aplysin and ( ) debromo aplysin have been prepared from wemcresyl methoxy methyl ethers... 

Aplysin and (—) debromoaplysin were prepared analogously via lithiation (t-BuLi) of the following optically active ether. 

The complete chemical and. ST-ray studies of laurinterol (140) have been published. In addition to laurinterol, debromolaurinterol and isolaurinterol (141) are also found in Laurencia intermedia Yamada. Aplysin (142), isolated from Aplysia kurodai Baba, can be derived from laurinterol by acid-catalysed cyclisation. A synthesis of both aplysin and debromoaplysin, involving suitable elaboration of the alcohol (143) has been reported.The synthesis of the methyl... 

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