Brevianamide synthesis

Cox RJ, Williams RM, The paraherquamides, brevianamides and asperparaline Laboratory synthesis and biosynthesis. An interim report, Acc Chem Res 36 127-139,2003. 

The same strategy has been used by Williams (90JA808) in his synthesis of brevianamide B. The aldehyde (82), prepared enantioselectively from L-proline, was converted to the silyl ether. Acylation of this (BuLi, ClC02Me) gave the carbomethoxy derivative as a mixture of diastereo-mers, which was alkylated by gramine. As before, an enolate alkylation (Sn2 ) on an allyl chloride derived from the above gave the tricyclic compound, which could be transformed to brevianamide B (Scheme 24). 

As part of on going efforts of Williams and his coworkers [46] to elucidate the biosynthesis of the core bicyclo[2.2.2] ring system of the related alkaloids the brevianamides [51], they have applied methodology originally developed for the stereocontrolled total synthesis of (-)-brevianamide B [52] to complete the first stereocontrolled total synthesis of (+)-PHB. 

Mould Metabolites.—A second synthesis of deoxybrevianamide E has been reported 300 in essence, it is similar to the earlier synthesis,306 the major difference being simply the order in which the various stages are effected. Photochemical oxidation of deoxybrevianamide E (34a) provides the first satisfactory laboratory synthesis of brevianamide E (34b), which was obtained in 42% yield, together with its stereoisomer, the alternative cis-fused cyclization product. The stereochemistry depicted in (34b) rests on a comparison of the n.m.r. spectra of these two stereoisomers.300... 

Details of Kametani s synthesis of deoxybrevianamide E and brevianamide E have been published.23... 

The semipinacolic rearrangement of 2-hydroxyimines has also been applied to the synthesis of 2-amino ketones which are not easily available by other methods (equation 43). ° An impressive example is the biomemetic formation of the spiroindoxyl brevianamide A (32 equation 44). ... 

In connection with the synthesis of naturally occurring 3a-hydroxypyrroloindole derivatives, e.g. brevianamide E and sporidesmin A, it is of interest to note that the photosensitized oxidation of Nb-methyltryptamine with singlet oxygen affords the 4a-hydroxyoxazinoindole (8a) and the 3a-hydroxypyrroloindole (8b) via the 3a-hydroperoxy compound (8c) (Scheme 2). 

Synthesis and biosynthesis of paraherquamides, brevianamides, and asperpar-alines, bicyclo[2.2.2]diazaoctane derivatives 03ACR127. 

A variety of other intramolecular alkylation reactions have been utilized in the synthesis of indole alkaloids. The acid-catalyzed conversion of the alkene (78) to the cyclic product (79) is a key step in the synthesis of a brevianamide (Equation (19)) <9378471 >. Similar acid treatment of the benzylic carbinol (80) yields the )S-carboline derivative (81) (Scheme 20) <88CC623>. 

Schkayantz JM, Woo JCG, SUiphaivanh P, Depew KM, Danishefsky SJ (1999) Total synthesis of gypsetin, deoxybrevianamide E, brevianamide E, and tryprostatin B novel constmctions of 2, 3-disubstituted indoles. J Am Chem Soc 121 11964-11975... 

The synthesis of [8-methylene- H2]deoxybrevianamide E was carried out by Wilhams et al. [19] to probe the intermediacy of deoxybrevianamide E in the biosynthesis of brevianamides A, B, and E. It was found that this substance, when fed to cultures of PeniciUium brevicompactum, was very efficiently incorporated into brevianamide E, brevianamide A, and brevianamide B. The data is reproduced in Table 3. 

Frebault, F.C. and Simpkins, N.S. (2010) A cationic cyclisation route to prenylated indole alkaloids synthesis of malbrancheamide B and brevianamide B, and progress towards stephacidin A. Tetrahedron, 66, 6585-6596. 

Proline derivative 71 was prepared and examined by Seebach in related alkylations (dr >95 5, Scheme 3.11) [62]. As an example of the usefid application of the derived products in total synthesis [64], Williams utilized 72 as a key intermediate for the construction of the alkaloid brevianamide B (73) [65]. 

---