Establishing Consensus Stereostructures for the Naphthoquinonopyrano‐γ‐lactone Natural Products (–)‐Arizonin B1 and (–)‐Arizonin C1 by Total Syntheses. Diastereocontrol of Oxa‐Pictet–Spengler Cyclizations by Protective‐Group Optimization

Abstract

Previous total syntheses of arizonin C1 (4) led to opposite assignments of its absolute configuration. Here, we report the fourth total synthesis thereof. In addition, we disclose the first total synthesis of arizonin B1 (3) proceeding differently than via arizonin C1. The stereocenters of the two targets stemmed from an asymmetric dihydroxylation and an ensuing oxa‐Pictet–Spengler cyclization. Their configurations were in line with Fernandes' assignments. Protective‐group variation in the substrate modulated the diastereoselectivity of the Pictet–Spengler cyclization between 77:23 in favor of a trans disubstitution at C‐3a vs. C‐5 – used for preparing the natural (–)‐arizonins C1 and B1 – and 100:0 in favor of a cis disubstitution – exploited for synthesizing the unnatural (+)‐5‐epi‐arizonins C1 and B1. All naphthalenes of the present study were derived from the (benzyloxy)methoxynaphthalenediol 19. It resulted from a Diels–Alder reaction of the aryne 17a with the siloxyfuran 18a.

Synthesis of Indofulvin Pseudo‐Natural Products Yields a New Autophagy Inhibitor Chemotype

“…Substrates containing basic moieties such as pyridines or tertiary amines were not suitable ( 3k and 3o ); however, amide‐ and N ‐Boc‐containing compounds were tolerated ( 3l – 3n ). The tolerance of an N ‐Boc functionality highlights the mild nature of the developed conditions relative to other oxa‐PS reactions in which Boc‐protected substrates either fail, [ 17 ] decompose, [ 24 ] or are not reported. Employing a challenging tropanone derivative successfully afforded 3p albeit in a low yield.…”

Design, synthesis, and evaluation of cytotoxic activities of arylnaphthalene lignans and aza‐analogs

“…Here too, the most significant obstacle in this scheme was the regioselective aromatic bromination as it has been strongly affected by the solvents and brominating agents used together with the substituents on the naphthalene core. [48][49][50][51][52][53][54][55][56][57][58][59][60][61] So, several parameters were examined and trials have been carried out to control the regioselectivity. The best conditions found were, on the one hand, reaction of 1 with pyridinium tribromide at 0°C in tetrahydrofuran (THF), [50] which gave the 3-bromo compound 15 in excellent yield without producing the 1-regioisomer (Scheme 6).…”

Total Synthesis of Actinorhodin

“…The third issue is rigorous stereocontrol in both enantio‐ and diastereomeric senses in the preparation of the monomer. However, seemingly simple stereocontrol of the 1,3‐ trans relationship has not been established: The often‐used strategy is acid‐mediated equilibration (Figure b),,,–,,– which only gives imperfect cis / trans ratios, inevitably requiring isomer separation.…”