Biomimetic Total Synthesis of Santalin Y

Strych, Sebastian; Journot, Guillaume; Pemberton, Ryan P.; Wang, Selina C.; Tantillo, Dean J.; Trauner, Dirk

doi:10.1002/anie.201411350

Cited by 55 publications

(13 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the biomimetic synthesis of santalin Y, Trauner considered 2 possible biosynthetic pathways. The first involves reaction between the benzyl styrene and an isoflavylium ion through a series of ionic intermediates (Scheme ; Path A) . While a viable biosynthetic pathway, Path A does not satisfactorily account for the stereoselectivity generated in the product.…”

Section: Discussionmentioning

confidence: 99%

Biomimetic syntheses of racemic natural products

Zask

Ellestad

2017

Chirality

View full text Add to dashboard Cite

Racemic natural products are rarely produced in plants and microorganisms and are thought to be the result of nonenzymatic, spontaneous reactions. These compounds are often highly complex with multiple contiguous chiral centers that present a challenge to organic synthesis. Formation of these racemates often occurs by cyclization reactions that can generate multiple stereocenters from achiral precursors. Biomimetic synthesis of these racemic natural products provides support for their proposed nonenzymatic spontaneous biosynthesis. These elegant syntheses also provide scalable and efficient routes to these complex natural products. Although the number of reported racemic natural products is relatively low, an isolated natural product that has a very small optical rotation has been shown to be a true racemate. Thus, the occurrence of racemic natural products could be more common than thought.

show abstract

Section: Discussionmentioning

confidence: 99%

Biomimetic syntheses of racemic natural products

Zask

Ellestad

2017

Chirality

View full text Add to dashboard Cite

show abstract

“…The resulting TBDMS ether 1 was next reacted with an excess of para-nitrobenzyl bromide (5 equiv.) under mild "Kuhn methylation" conditions (i.e., the use of Ag 2 O as electrophilic catalyst and base), 33 to readily introduce the NTR-labile protecting group into the 2-OH position, without premature deprotection of the 4-OH group. The full-protected benzaldehyde derivative 2 was condensed with either benzothiazole-2-acetonitrile or malonitrile in EtOH and in the presence of a catalytic amount of piperidine, to give the Knoevenagel adducts which were desilylated by treatment with TBAF in THF.…”

Section: Synthesis Of Bis-o-protected 24-dihydroxycinnamonitrile Deri...mentioning

confidence: 99%

Dual enzyme-responsive “turn-on” fluorescence sensing systems based on in situ formation of 7-hydroxy-2-iminocoumarin scaffolds

Debieu

Romieu

2015

Org. Biomol. Chem.

View full text Add to dashboard Cite

A new strategy for the simultaneous fluorogenic detection of two distinct enzyme activities namely hydrolase (amidase or esterase) and reductase is described. This innovative biosensing method is based on the powerful "covalent-assembly" principle that involves in situ synthesis of a fluorophore from a non-fluorescent caged precursor and through domino reactions triggered by the two analytes of interest. To establish this approach, penicillin G acylase (PGA) (or pig liver esterase (PLE)) and nitroreductase (NTR) were chosen as model enzymes, and original bis-O-protected 2,4-dihydroxycinnamonitrile derivatives acting as dual-reactive probes readily convertible to highly fluorescent 7-hydroxy-2-iminocoumarin scaffolds upon reacting with the two selected enzymes were synthesised. The two phenolic groups available within the core structure of these probes play a pivotal role in generating iminocoumarin scaffold through an intramolecular cyclisation reaction (hydroxyl group in C-2 position) and in enhancing its push-pull character (hydroxyl group in C-4 position). Their orthogonal and temporary protection with two different enzyme-labile masking groups is the cornerstone in the design of this novel class of fluorogenic "turn-on" probes. Their evaluation using fluorescence-based in vitro assays and HPLC-fluorescence/-MS analyses have enabled us both to demonstrate the claimed activation mechanism (in particular the specific order in which the two enzymes react with the probe) and to highlight the potential utility of these advanced chemical tools in multi-analyte sensing applications.

show abstract

“…Yet the structures of various natural products are suggestive of an involvement of 1,3‐dipolar cycloadditions in the corresponding biosynthetic pathways (Scheme ) 2. Such intriguing models have been supported by the elegant biomimetic total syntheses of santalin Y, intricarene, and alsmaphorazine B, for example 2a–c. Nonetheless, the involvement of enzymes remained in question since density functional theory (DFT) calculations suggested that nitrone–alkene [3+2] cycloaddition reactions may occur during the biosynthesis of some alkaloid natural products without any enzymatic intervention 2d.…”

Section: Methodsmentioning

confidence: 99%