Allopumiliotoxins syntheses

Comins et al. <20010L469> achieved the synthesis of the same allopumiliotoxin 267A 215 by a stereoselective alkynylation of the appropriately substituted 4-MeO-pyridine 226. The C-6 side chain is introduced by an aldol condensation between an aldehyde and indolizidinone 227 (Equation 17). 

In some instances an allylic oxygen bond can undergo reductive cleavage. For example, in a synthesis of Allopumiliotoxin 339A, Overman and co-workers showed that the reductive cleavage product 1403 was the major product on attempted deprotection of the two benzyl ethers in 140.1 with lithium in liquid ammonia at -78 C for more than 5 minutes [Scheme 4.140]. However, by terminating the reaction after 2 minutes, the desired triol 1403 was obtained in 86% yield. 

A novel approach has been developed towards the total synthesis of (+ )-allopumiliotoxin 339A (112), a minor consituent of skin extracts from the family of Panamanian poison frogs Dendrobates auratus, based on an intramolecular chromium(II)-mediated cyclization. Ketone 107, after a Homer—Emmons condensation, DIBAL reduction, and conversion to the bromide 109, is homologated based on Evans alkylation procedure [45] and transformed through a series of efficient reactions into the iodoolefin 110. 

A new synthesis of the indolizidine alkaloid (+)-allopumiliotoxin 323B was achieved through intramolecular 13-DC of the (Z)-A -alkenylnitrone 84. The major cycloadduct 85,... 

Heterocycles can be formed through C-heteroatom bonding occuring via Pd-catalyzed cyclization (Scheme 18). This latter example, a 6-endo-trig cyclization, is the key step in the allopumiliotoxin 339B synthesis. ... 

Scheme 301 (TCC = rrans-2-(a-cumyl)cyclohexyl). Synthesis of (+)-allopumiliotoxin 267A (1718) by Comins et Reagents and conditions (a) CICOj—TCC (b) LiC= CC02Et, THF, -78 °C, then H3O+ (c) Hj, Pd/C, EtOH (d) LiOMe, MeOH, reflux, 18 h (e) Pb 0Ac)4, AcOH, m-C6H4(CF3)2, reflux (f) HCO2H, reflux, 2 h (g) K-Selectride (h) UAIH4 (i) Swern oxidation (j) PhjCLi (2 equiv.) (k) (/ )-2-methylhexanal (I) DBU, DMAP, TFAA (m) Me4NBH(OAc)3, Me2CO-AcOH.

Scheme 302 Key steps in the synthesis of (+)-allopumiliotoxin 267A (1718) by Wang et al. Reagents and conditions (a) Pr2NEt, MeCN, reflux, 24 h (b) n-BuLi (2 equiv.), THF, -78 °C, 30 min (c) Me4NBH(0Ac)3.

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