Recent Advances in the Synthesis of Angucyclines

Abstract

The different strategies recently reported to construct the tetracyclic skeleton of angucyclines are presented: Diels-Alder and Friedel-Crafts reactions, nucleophilic additions, free radical annulations, rearrangements of cyclobutenones and cobalt-mediated [2+2+2] cycloadditions. Among the asymmetric approaches, the most efficient corresponds to Diels-Alder reactions including the use of chiral catalysts, enantiopure vinyl cyclohexenes as dienes, synthesized from quinic acid or (S,S)-[(p-tolylsulfinyl)methyl]-pquinol, and chiral dienophiles such as (S,S)-2-(p-tolylsulfinyl)-1,4-naphthoquinones.

Biomimetic synthesis of galantamine via laccase/TEMPO mediated oxidative coupling

“…30 Galantamine 3 was nally obtained from 5 by a two steps procedure (Scheme 2), including the synthesis of N-formyl-1-bromo-narwedine 6 by treatment with 1,8diazabicyclo[5.4.0]undec-7-ene DBU (91%), followed by conventional reduction with both L-selectride and lithium aluminum hydride (61%). 7,31,32…”

Synthesis of orthogonally protected d-olivoside, 1,3-di-O-acetyl-4-O-benzyl-2,6-dideoxy-d-arabinopyranose, as a C-glycosyl donor

“…3,4 These antibiotics have attracted much attention due to the wide range of biological activities that they exhibit, which include antibacterial, 5-7 antiviral, 8 antitumour [9][10][11] and enzyme inhibition properties. 12 2,6-Dideoxy-and 2,3,6-trideoxy-sugars such as D-olivose (1) and L-rhodinose (2) are present in many of these antibiotics and may be attached at different positions of the angucycline framework either by C-or O-glycosidic linkages. 1 Urdamycin B (3), a secondary metabolite of Streptomyces fradiae, shows glycosylation typical of the Cglycosyl angucycline subgroup.…”

Cascade assembly of the benz[a]anthraquinone ring system common to the angucycline antibiotics

“…These discoveries have stimulated interest in the total synthesis of this sub-class of aromatic polyketide natural products. 2 The Diels-Alder and Hauser type annulations have figured prominently among synthetic strategies leading to the chemical synthesis of a variety of angucyclinones. Moore 3a–c and others 3d–f have employed a cascade of pericyclic reactions starting from benzocyclobutenes to construct the central quinone (C ring) in order to complete benzoanthraquinone ring assembly ( 1, 2 , Scheme 1).…”