Botryodiplodin synthesis

Allenyl ethers are useful key building blocks for the synthesis of a-methylene-y-butyrolactones [129, 130], The synthesis of the antileukemic botryodiplodin was accomplished with the crucial steps briefly presented in Scheme 8.56. Bromoallenyl ethers 225 were easily prepared by base-induced isomerization from the corresponding /3-bromoalkyl alkynyl ether compounds and then subjected to electrophilic bro-mination with NBS. The resulting acetals 226 were converted into 2-alkoxy-3-methy-lenetetrahydrofurans 227 by dehydrohalogenation of the alkenyl bromide unit to an alkyne and subsequent radical cyclization employing tributyltin hydride [130],... 

Due to the increased reactivity of the aldehyde, alkyl-substituted nitroolefins can also be used as substrates. Nevertheless, these reactions are usually low-yielding and afford moderate selectivity. Alexakis has shown, however, that the bispyrrolidine 5-catalyzed additions may be used in multistep synthesis. The addition of propionaldehyde 34 to nitroolefin 33 resulted an approximate 2 3 mixture of anti/syn isomers in 92% yield and in high ee (93%), allowing the asymmetric synthesis of (—)-botryodiplodin (Scheme 2.46) [23b]. 

Stereoselective synthesis of (+ )-botryodiplodin was carried out by a radical cyclization of dibromoacetal (203) containing an allene group, with Bu3SnH initiated by Et3B, through the 5-exo-trig cyclization, and the subsequent debromination with bulky... 

Similar bromohydrin interconversions were demonstrated in sugar-based epoxide rearrangements. The unsaturated aldehydes formed in these reactions are useful for further elaboration, as shown in a recent synthesis of botryodiplodin. 

The reaction has been used in a convenient synthesis of the antibiotic and antileukemic agent botryodiplodin (97)."°... 

Regarding substrate scope, catalysts 22a, 30,37, and 40-44 (Fig. 2.4) are efficient promoters for the Michael addition of aldehydes to p-alkyl substituted nitrooleflns. Taken advantage of the good activity exhibited by catalyst 30 in this process, Alexakis et al. have achieved the total synthesis of the mycotoxin (-)-botryodiplodin [73], process which involves an attractive Michael addition between an aldehyde and an a-substituted nitroolefin (Scheme 2.21). 

Scheme 36 Asymmetric conjugate addition to nitroalkene 151 in the synthesis of (—)-botryodiplodin (155)...

Andrey O, Vidonne A, Alexakis A (2003) Organocatalytic Michael Addition, a Convenient Tool in Total Synthesis. First Asymmetric Synthesis of (-)-Botryodiplodin. Tetrahedron Lett 44 7901... 

SCHEME 11.19. Addition to trisubstituted nitroolefin and the synthesis of botryodiplodin. 

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