Lankacidin antibiotics

In their synthesis of lankacidin antibiotics, an insertion reaction of an azidoformate-derived acyinitrene on the electron-rich dihydrofuran 290 to introduce the sterically hindered C-3 amino appendage in the macrocyclic framework. The oxazoline formation is totally stereospecific with the... 

Sedecamycin is an example with a 17-membered ring that belongs to the lankacidin group of antibiotics. It is a neutral compound since, unlike other macro-lides containing amino sugars, sedecamycin does not contain amino sugar moieties (93). 

The implementation of this methodology for a synthesis of advanced macro-cyclic precursors of antitumor antibiotics lankacidins, which posses a carbocyclic structure, has been reported by Thomas [77]. In such a route, Scheme 13, one of the key steps is the ring opening of the (3-lactam nucleus in 30 by methanol, assisted by KCN, to give the corresponding (3-amino ester intermediate 31. The latter, upon cyclization and protecting group manipulation, renders 32, which on subsequent elaboration affords lankacidin C. 

In the final step of a synthesis of the antitumour antibiotic Lankacidin C, Kende and co-workers55 were faced with the difficult deprotection of a bis-TBS ether [Scheme 4.35] without cleavage of the delicate pyrandione ring. Desilylation failed with all variants of fluoride or HF, but it was finally achieved using aqueous formic acid at 20 °C for 3 h to produce Lankacidin C in 82% yield. 

Various examples of use of alkenyltin/vinyl iodide couplings in natural-product synthesis have been provided Evans and Black [33] have obtained the macrolide insecticide (+)-A83 453A [(+)-lepicidin A] (Scheme 4-7), Burke et al. the ionophore antibiotic X-14547A [34] (Scheme 4-8), Kende et al. [35] lankacidin C (Scheme 4-9), while Han and Wiemer [36] have used the combination alkenyltin/vinyl triflate in the total synthesis of (+)-jatrophone. 

Thomas et al. [90] prepared two 17-membered macrocyclic tetraenes that are possible precursors of the natural product lankacidin C in this case, a trisubstituted vinyl iodide was involved, and the amount of Pdjdbaj required was relatively high (30%). Toshima et al. [91] reported a highly stereoselective total synthesis of the macrolide antibiotic concanamycin F again, intermolecular and intramolecular vinyl-vinyl couphngs were used. WhUe liCl was used as an additive in the former, it was replaced by DIPEA in the latter. In a recent pubUcation [49], Toshima et al. 

The simple procedure and the high selectivity encouraged application in natural product synthesis [235], and an important intermediate en route to the antitumor antibiotic lankacidin [235a] is given as an example (see 625). 

D-Arabinose provides the backbone of the highly functionalized acyclic unit 74 (sugar carbons are numbered) which has been used by Kende in the first synthesis (34 steps) of (-)-lankacidin C 75, an anti-tumour macrolide antibiotic. ... 

A striking application of Seebach s and Prater s approach for the installation of a quaternary stereogenic center can be found in Williams total synthesis of the antitumor antibiotic lankacidin C (62, Scheme 3.9) [59]. Treatment of 60 with excess NaHMDS and prenyl bromide gave 61 in 80% yield... 

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