A Chemoenzymatic Route to the (+)-Form of the Amaryllidaceae Alkaloid Narseronine

Abstract

The enzymatically derived and enantiopure cis-1,2-dihydrocatechol 1 has been converted, over 14 one-pot operations, into the (þ)-form of the alkaloid narseronine (2). The present study, which complements earlier work that established a route from metabolite 1 to enantiomer (À)-2, involves an N-bromosuccinimide/tri-n-butyltin hydride-mediated cyclisation reaction to construct the unsaturated B-ring lactone of the target compound.

The Exploitation of Enzymatically‐Derived cis‐1,2‐Dihydrocatechols and Related Compounds in the Synthesis of Biologically Active Natural Products

“…We have also employed related Suzuki‐Miyaura cross‐couplings in the synthesis of the enantiomers of other Amaryllidaceae alkaloids including ent ‐narciclasine ( 60 ), ent ‐clividine ( 61 ), the enantiomer, 62 , of the structure originally assigned to nobilisitine A, the enantiomer, 63 , of the true structure of the same alkaloid as well the configurationally related compounds 64 and 65 either of which could represent the structure of narseronine, a recently isolated alkaloid for which no optical rotation data have been reported. The fact that both enantiomers 64 and 65 were prepared from the same starting material, viz .…”

Amaryllidaceae Alkaloids from Clivia miniata (Lindl.) Bosse (Amaryllidaceae): Isolation, Structural Elucidation, and Biological Activity

“…NOESY correlation was observed for H-3 a and H-5 , suggesting a pseudoaxial orientation of allylic H-5 . Determination of H-5 orientation was supported by comparison with related structures described in the total synthesis of narseronine [34] that were analyzed, among other techniques, by X-ray crystallography. C5-epimers were perfect comparison targets (see Table S2).…”

The role of biocatalysis in the asymmetric synthesis of alkaloids – an update

“…In an interesting example of stereodivergent synthesis, Banwell and co-workers prepared (+)-narseronine ( ent -104) from the commercially available diol 95, 83 after having previously used the same building block to obtain the (−)-enantiomer of this Amaryllidaceae alkaloid. 84 The sequence followed to arrive at ent -104, however, resembles more closely the one developed in another synthetic endeavour of Banwell's group, the preparation of (+)-clividine: 85 Diol 95 was converted into the vinylic bromide 155 via a five-step sequence before being coupled with boronate 156 in a Suzuki reaction ( Scheme 19 ).…”