Vernolepin

Aqueous intermolecular Diels-Alder chemistry vernolepin revisited [16e]... 

Example Compound (27) was needed for synthesis of analogues of vernolepin, an anti-tumour compound. Robinson disconnection suggests unsymmetrical ketone (28)... 

Grieco utilized an aqueous intermolecular Diels-Alder reaction as the key step in forming the AB ring system of the potent cytotoxic sesquiterpene vernolepin. 87 Cycloaddition of sodium ( >3,5-hexa-dienoate with an a-substituted acrolein in water followed by direct reduction of the intermediate Diels-Alder adduct gave the desired product in 91% overall yield (Eq. 12.28). 

Complete details of the previously reported total synthesis of the antitumour elemanolides vernolepin (363) and vernomenin (364) (Vol. 7, p. 97) have been published.Other research groups have reported the synthesis of compounds (365)—(367) which could be of considerable value as intermediates in alternative synthetic routes to vernolepin and vernomenin.The antitumour activity of... 

Synthesis of a m-decalin system by the asymmetric cyclization[38] has been carried out with high enantioselectivity[142,143,147,148], Using BINAP as a chiral ligand, 91% ee was achieved in the asymmetric cyclization of 177 to give 178. In order to achieve an efficient asymmetric cyclization, selection of the reaction conditions is crucial, and sometimes added Ag salts play an important role[148], A catalytic asymmetric cyclization of 179 to prepare the key intermediate enone 180 for vernolepin synthesis has been carried out[149]. Highly efficient asymmetric cyclization of 181 to give the tetralin system 182 has been applied to the synthesis of (-)-eptazocine (183)[150], Hydrindans are synthesized in 86% ee[151]. 

In one of the last transformations in a multistep synthesis of 1,2-dihydro-8-ep/-vernolepin (43), nucleophilic intramolecular substitution at an iodomethyl group was promoted by heating an ester precursor with an equivalent of NaOAc in DMF (Equation (18)) <95TL3ii>. Molecular mechanics analysis of the precursor produced a minimum energy conformer that showed the hydroxyl substituent too distant from the iodomethyl group to have interfered with this high yield transformation. 

Drugs to combat cancer act on a range of biochemical pathways, but most commonly on processes that cancerous cells need to use to proliferate rapidly, one class attacks DNA polymerase, an enzyme needed to make the copy of DNA that has to be provided for each new cell. Helenalin and vernolepin are two such drugs, and if you look closely at their structure you should be able to spot two ot,p-unsaturated carbonyl groups in... 

Three research groups have developed synthetic routes which provide the basic A/B ring system of the plant-growth-inhibitory seco-eudesmanolides (elemanes) vernolepin (230), vernodalin (231),106 and vernomenin (232). In one approach107... 

In their search for suitable synthetic applications of their methodology, Shibasaki and coworkers spared no efforts and carried out an 18-step synthesis of lactone 35, which represents an early intermediate of Danichefsky s synthesis of (-i-)-vernolepin (Scheme 10) [14]. First, the ester 31 is transformed via 32 into the allylic alcohol 33, which is then cyclized with good enantioselectivities to yield the enone 34 (which is initially formed as an enol by /i-H-elimination). 

Scheme 10 Formal total synthesis of (+)-vernolepine according to M. Shibasaki.

This (formal) total synthesis of vernolepin deserves attention because of the elegance of the key step, which generates 34 in non-racemic form. However, the long and inefficient overall sequence impairs the competitiveness of the synthesis. 

Although the synthetic challenge of vernolepin (430) and vernomenin (431) has been met by a number of groups, several interesting papers in this area have... 

Ozonolysis results in cleavage of the double bond as in the case of 42 (equation 28) ". Other examples are the syntheses of the ambrosia bettle pheromone lineatin (43, equation 29) and vernolepin (44, equation 30). ... 

This chemistry is part of a synthesis of the antitumour agent vernolepin by S. Danishefsky and group, J. Am. Chem. Soc., 1976, 98, 3028,... 

The antitumour activity of the elemanolides vernolepin (393) and vernomenin (394) has stimulated several research groups to solve the problems associated with... 

Depending on the catalytic species, palladium-catalyzed mono- and dicarbonyl-ation of alkynes may be achieved. Monocarbonylation of acetylenic alcohols in the presence of thiourea is an elegant route to a-methylene-7-butyrolactone 202, the structure of which is widely distributed in certain natural products98,99). The synthesis of a vernolepine derivative (203) has been attempted by this method 100l Pro-... 

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