Convergent and Biomimetic Enantioselective Total Synthesis of (−)-Communesin F

Abstract

The first biomimetic enantioselective total synthesis of (−)-communesin F based on a late-stage heterodimerization and aminal exchange is described. Our synthesis features the expedient diazene–directed assembly of two advanced fragments to secure the congested C3a–C3a′ linkage in three steps, followed by a highly efficient biogenetically inspired aminal reorganization to access the heptacyclic communesin core in only two additional steps. Enantioselective syntheses of the two fragments were developed, with highlights including the catalytic asymmetric halocyclization and diastereoselective oxyamination reactions of tryptamine derivatives, a stereoselective sulfinimine allylation, and an efficient cyclotryptamine–C3a-sulfamate synthesis by either a new silver–promoted nucleophilic amination or a rhodium–catalyzed C–H amination protocol. The versatile synthesis of the fragments, their stereocontrolled assembly, and the efficient aminal–exchange as supported by in situ monitoring experiments, in addition to the final stage N1′-acylation of the communesin core provide a highly convergent synthesis of (−)-communesin F.

Oxidative Cyclization in Natural Product Biosynthesis

“…Four contiguous stereocenters run through the junction of two fragments. While numerous total syntheses of communesin have been reported, 77–87 the biosynthetic pathway was only recently uncovered from P. expansum and was shown to be highly efficient (Scheme 15). 88,89 The two indole-containing building blocks are tryptamine ( 50 ) derived from decarboxylation of L-tryptophan, and (−)-aurantioclavine ( 53 ) derived from the decarboxylative cyclization of 4-dimethylallyltryptophan.…”

“…87 In their strategy, the two indole fragments were first synthesized as azepine 68 and cyclotryptamine 69 . Coupling of the two fragments can yield the sulfamide 70 on a gram scale.…”

Nickel‐Catalyzed Barton Decarboxylation and Giese Reactions: A Practical Take on Classic Transforms

“…[3] These thiohydroxamic anhydrides can be conveniently obtained when ubiquitous carboxylic acids are coupled with pyrithione (readily accessible from industrial feedstock). [6,7] The low stability of Barton esters stemming from their photo-and thermal sensitivity adds another layer of difficulty.A lthough alternative reductants such as tris(trimethylsilyl)silane [8] or chloroform have been introduced for the decarboxylation reaction, [9,10] the other problems have remained largely unmitigated. [4] Reductive decarboxylation with tin hydride or an alkyl thiol (1 to 2)a nd Giese reaction with Michael acceptors (1 to 3)a re two notable examples.T he thiocarbonyl group,i nB artonso wn words,a cts as a" disciplinary group", conferring the process chemoselectivity and functional group compatibility,l eading to numerous applications over four decades.A lthough photoinduced electron transfer processes with carboxylic acid derivatives have been surveyed as an alternative to Barton esters beginning with Okadasw ork in 1988, [5] these methods require specialized equipment, expensive catalysts,and prolonged reaction times.…”

Enzymkaskadenreaktionen in der Biosynthese

“…Bei der Bildung der neuen C-N-Bindung wird O 2 reduziert, aber nicht in das Produkt-Gerüst eingebaut. [89] 6.1.1. [87] Tr yptophan ist als Primärmetabolit die Vorstufe zur Bildung von Tr yptamin durch Decarboxylierung und danach von Aurantioclavin durch Prenylierung am C4-Atom und Cyclisierung des Allyl-Kations.…”