Verrucarines

Verdazyls — see 1,2,4,5-Tetrazinyl, 3-hydro-Verrucarin E synthesis, 1, 432 Vertical stack conductors, 1, 351 Veterinary products... 

The naturally occurring mycotoxins, 125 and 126, produced mainly by fungi" and implicated in the variety of toxicoses in man and animals99 100, have been tritium labelled101 (equations 46 and 47) for use in toxicology metabolism and pharmacokinetic studies. Position 15 in verrucarol and position 16 in verrucarin A have been tritium-labelled, because they should not suffer from the loss of labelling protons during the... 

The power of Muchowski s method is seen by the fact that these bromopyrroles can be subjected to bromine-lithium exchange to afford the versatile 3-lithio species that can be quenched with a variety of electrophiles in good to excellent yields [18-21]. This is illustrated by a synthesis of verrucarin E (11) [19]. 

Baccharis cordifolia Certopicnidium baccharidicola rodicin A, D, E and H, verrucarin A and J 203, 246... 

Universitat-Gesamthochschule Paderbom Warburger StraBe 100 D-33098 Paderborn Telefon (05251) 60-2172 Isosclerone Mollisin Patulin Penicillic acid Mycorrhizin A Aurantiogliodadin (-)-3,4-Dihydro-6,8-dihydroxy-3-methylisocoumarin Epicorazine A Oosporein Verrucarin A Verrucarin B Mellein Methylmellein... 

Reaction of an -substituted pyrrole with an alkynic dienophile provides access to a 3,4-disubstituted pyrrole through a Diels-Alder/retro-Diels-Alder cycloaddition process (73CJC1089). The 3,4-pyrroledicarboxylic ester (206) prepared in this way has been converted to the antimitotic agent Verrucarin E (207 Scheme 44). 

Anderson and co-workers86 used the cycloaddition of acetylenic esters to 19a and 19 (R = COPh) in the synthesis of the antimitotic agent Verrucarin E (28). The pyrrole 19a and DMAD gave 35% of 21a, whereas 19 (R = COPh) gave 67% of 21 (R = COPh) and 23% of recovered starting material 1-benzoylpyrrole gave 54% of 29 with DEAD. Further transformations produced the natural product. 

Another regioselective addition to an epoxide was used as one step in a synthesis of the r-butyldiphenylsilyl ether (7) of verrucarinic acid from 5.3 The diol was converted into the optically active epoxy alcohol by the Sharpless method (10, 64-65) and then oxidized to the epoxy acid 6 by the new ruthenium-catalyzed oxidation of Sharpless et al. (this volume). This epoxy acid undergoes almost exclusive / -addition with trimethylaluminum to give the desired product 7. 

Oxidation of hemiacetals.1 Pyridinium dichromate in DMF effects a novel oxidative cyclization of the aldehyde 1 to the macrocyclic lactone verrucarin T (2a). The conversion is believed to involve cyclization to a hemiacetal (2b) followed by oxidation to 2a. Manganese dioxide does not oxidize 1, and a variety of other oxidants attack the dienic ester side chain. 

The successful synthesis of optically active 7 then led to the first synthesis of verrucarin A (8), a macrotrilactone with significant cytostatic activity. The synthesis involved esterification of the primary alcohol of verrucarol (the tricyclic fragment) with the acetate of 7 (DCC, 4-pyrrolinopyridine) and then with a protected derivative of (E, Z)-muconic acid. After deprotection (Bu4NF), lactonization was effected by the Mitsunobu procedure (7,405-406). 

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