Jochen Becker

Asymmetric total synthesis and X-ray crystal structure of the cytotoxic marine diterpene (+)-vigulariol.

belongs to the impressively large class of the cladiellin (eunicellin) diterpenes, of which many bear interesting biological activities. (+)-1 has shown to exhibit cyctotoxity against A 549 (human lung adenocarcinoma) cell culture at an IC50 of 18.33 mgmL . Two other soft-coral diterpenes sclerophytin A (2) and polyanthellin A (3) have shown high cytotoxicity and antimalarial activity, respectively. Their attractive molecular architectures and their diverse biological activities previously led to several ingenious total syntheses of some members of this natural product family by the research groups of Paquette, Overman, Crimmins, and Kim. (+)-1 was formed as a by-product during Paquette and coworkers3 synthesis of 2 before it was known to be natural product and was therefore not fully characterized. The total synthesis of rac-1 over 20 linear steps was quite recently published by Clark et al. Herein we present a short and efficient total synthesis and, in addition, the solid-state structure of enantiomerically pure (+)-vigulariol (1), by applying our previous synthetic and mechanistic investigations. As depicted in Scheme 1, (+)-vigulariol (1) could be elaborated by stereoselective epoxidation of the C=C double bond of tricycle 4. Deprotection of the hydroxy group was

Total Synthesis and Biological Evaluation of (+)- and (–)-Bisanthraquinone Antibiotic BE-43472B and Related Compounds

The bisanthraquinone antibiotic BE-43472B [(+)-1] was isolated by Rowley and co-workers from a streptomycete strain found in a blue-green algae associated with the ascidian Ecteinascidia turbinata and has shown promising antibacterial activity against clinically derived isolates of methicillin-susceptible, methicillin-resistant, and tetracyclin-resistant Staphylococcus aureus (MSSA, MRSA, and TRSA, respectively) and vancomycin-resistant Enterococcus faecalis (VRE). Described herein is the first total synthesis of both enantiomers of this bisanthraquinone antibiotic, the determination of its absolute configuration, and the biological evaluation of these and related compounds. The developed synthesis relies on a highly efficient cascade sequence involving an intermolecular Diels-Alder reaction between diene (R)-61 and dienophile 55, followed by an intramolecular nucleophilic aromatic ipso substitution. Late-stage transformations included a remarkable photochemical alpha,beta-epoxyketone rearrangement [80 --> (+)-1]. Interestingly, the unnatural enantiomer [(-)-1] of antibiotic BE-43472B exhibited antibacterial properties comparable to those of the natural enantiomer [(+)-1].

Total Synthesis and Absolute Configuration of the Bisanthraquinone Antibiotic BE-43472B†

An-T-biotic: The first total synthesis of the T-shaped bisanthraquinone natural product BE-43472B was accomplished and its absolute configuration assigned. Key transformations in the pivotal cascade sequence include a Diels-Alder reaction, a hemiketal formation, and a nucleophilic aromatic ipso substitution.

Origins of Regioselectivity of Diels–Alder Reactions for the Synthesis of Bisanthraquinone Antibiotic BE-43472B

The regioselectivities of several Diels-Alder reactions utilized en route to bisanthraquinone antibiotic BE-43472B are examined using density functional theory calculations. These reactions involve highly substituted dienes and juglone dienophiles, and there is an opposite regiochemical outcome for Diels-Alder reactions with beta-aryl substituted juglones when compared to reactions of unsubstituted juglone. In this article, the effect of an aromatic conjugating group bonded to juglone is explored.

Synthesis of the Carboline Disaccharide Domain of Shishijimicin A

A synthetic route to the carboline disaccharide domain (2) of shishijimicin A (1) has been developed. The convergent synthesis relies on a novel application of the Reetz-Müller-Starke reaction to form the central, sulfur-bearing quaternary carbon center and addition of the carboline structural motif as a dianion to a disaccharide aldehyde fragment.