Total Synthesis of (−)-Tuberostemonine

Abstract

The first total synthesis of the complex pentacyclic Stemona alkaloid tuberostemonine was accomplished in 24 steps and in 1.4% overall yield from a hydroindole intermediate which is readily obtained in three steps from Cbz-l-tyrosine. An innovative synthetic strategy was applied that relays the single stereocenter of the amino acid precursor into nine of the ten stereogenic carbons of the target molecule. Among the highlights of the synthetic methodology are the 3-fold use of ruthenium catalysis, first in an azepine ring-closing metathesis and then in an alkene isomerization followed by a cross-metathesis propenyl-vinyl exchange, as well as the stereoselective attachment of the gamma-butyrolactone moiety to the core tetracycle by use of a lithiated ortho ester.

Synthesis and receptor profiling ofStemonaalkaloid analogues reveal a potent class of sigma ligands

“…Stemona alkaloids 1-3 have been the targets of successful synthetic campaigns by this (24)(25)(26) and other groups (27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37), although the synthesis of neotuberostemonine 4 has yet to be realized. Our own interest in this class of natural products was driven initially by the challenges presented by these alkaloids in such a total synthesis context.…”

Synthesis and Biological Properties of the Cytotoxic 14‐Membered Macrolides Aspergillide A and B

“…> 95:5 by NMR), which was subsequently protected as its triethylsilyl derivative 8. Isomerization of the terminal olefinic bond to the internal position was achieved by means of Wipf's adaptation of the catalytic method reported by Roy et al [22] With the aid of this procedure, compound 8 was converted into its isomer 7 in high yield.…”

Diene, Enyne, and Diyne Metathesis in Natural Product Synthesis

“…When alcohol 106 was treated with second-generation catalyst C, the ring closure proceeded smoothly leading to 103 in nearly quantitative yield. A further example of the rapid progress in Ru-catalyzed metathesis reactions is Wipf 's total synthesis of (-)-tuberostemonine (113) [71]. This complex polycycle belongs to the family of Stemona alkaloids, which cover a broad range of biological activities including applications in Eastern folk medicine against pulmonary tuberculosis and bronchitis.…”

“…Scheme 21 Threefold use of ruthenium catalysts in the first total synthesis of Stemona alkaloid tuberostemonine (113) [71] …”