Biocatalytic Organic Synthesis of Optically Pure (<i>S</i>)-Scoulerine and Berbine and Benzylisoquinoline Alkaloids

Alkynylation reactions of N-protected tetrahydroisoquinolines have been performed using several different protocols of cross dehydrogenative coupling. Initially, a CuCl-catalyzed method was investigated, which worked well with three different N-protecting groups, namely phenyl, PMP, and benzyl and t-BuOOH as oxidant in acetonitrile as solvent. The peroxide could then be replaced by simple air and acetonitrile for water, leading to an overall very environmentally friendly protocol. Finally, a decarboxylative alkynylation protocol starting from alkynoic acids was also developed using again air as oxidant. This avoids the use of gaseous alkynes in the introduction of short-chained alkyne substituents.Graphical abstract

show abstract

“…M.p. : 27–35 °C; TLC: R f = 0.79 (PE:Et 2 O = 5:1); NMR data were in agreement with the literature [32]. …”

Section: Methodssupporting

confidence: 87%

Improved simplicity and practicability in copper-catalyzed alkynylation of tetrahydroisoquinoline

2016

View full text Add to dashboard Cite

show abstract

“…Hence, we investigated a modified four-step synthesis (Scheme 3), in which isovanillin (13) was benzyl-protected under standard conditions [20] and oxidized in a Baeyer-Villiger oxidation by using 3-chloroperbenzoic acid (mCPBA). Hence, we investigated a modified four-step synthesis (Scheme 3), in which isovanillin (13) was benzyl-protected under standard conditions [20] and oxidized in a Baeyer-Villiger oxidation by using 3-chloroperbenzoic acid (mCPBA).…”

Section: Resultsmentioning

confidence: 99%

“…Crude formate 17 was directly saponified with aqueous sodium hydroxide to give phenol 18. [20] ; (k) mCPBA (1.5 equiv. This compound again turned out to be not very stable, but it could be significantly stabilized by addition of a few drops of solvent.…”

Section: Resultsmentioning

confidence: 99%

Revision of the Structure and Total Synthesis of Altenuisol

2012

View full text Add to dashboard Cite

A total synthesis of the reported structure of altenuisol is described. Comparison of the 1H NMR spectra of the synthesized compound and of the natural product revealed that the originally proposed structure was not correct. Consequently, two constitutional isomers were synthesized. The spectra of one of these compounds – a structure originally proposed as the structure of altertenuol – matched perfectly with the spectra of the natural product. The total synthesis of altenuisol was thus achieved starting with phloroglucinic acid and protocatechuic aldehyde in 10 steps and in 23 % yield, where the longest linear sequence consisted of 6 steps. The key step was a Suzuki coupling with concomitant formation of the lactone ring. Whether altertenuol is identical with altenuisol could not be decided.

show abstract

“…This VAO-type oxidase enzyme catalyses the biotransformation of (S)-reticuline into (S)-scoulerine through the formation of an intramolecular C-C bond at the expense of molecular oxygen. Scoulerine and related compounds often exhibit interesting biological properties (Schrittwieser et al 2011b). Therefore, reticuline oxidase has been thoroughly studied for its use in the synthesis of such alkaloids.…”

Section: Flavoprotein Oxidases In Biotechnologymentioning

confidence: 99%

Flavoprotein oxidases: classification and applications

Dijkman

Gonzalo

Mattevi

et al. 2013

Appl Microbiol Biotechnol

132

106

View full text Add to dashboard Cite

This review provides an overview of oxidases that utilise a flavin cofactor for catalysis. This class of oxidative flavoenzymes has shown to harbour a large number of biotechnologically interesting enzymes. Applications range from their use as biocatalysts for the synthesis of pharmaceutical compounds to the integration in biosensors. Through the recent developments in genome sequencing, the number of newly discovered oxidases is steadily growing. Recent progress in the field of flavoprotein oxidase discovery and the obtained biochemical knowledge on these enzymes are reviewed. Except for a structure-based classification of known flavoprotein oxidases, also their potential in recent biotechnological applications is discussed.

show abstract

Biocatalytic Organic Synthesis of Optically Pure (S)-Scoulerine and Berbine and Benzylisoquinoline Alkaloids

Cited by 69 publications

References 97 publications

Improved simplicity and practicability in copper-catalyzed alkynylation of tetrahydroisoquinoline

Improved simplicity and practicability in copper-catalyzed alkynylation of tetrahydroisoquinoline

Revision of the Structure and Total Synthesis of Altenuisol

Flavoprotein oxidases: classification and applications

Contact Info

Product

Resources

About