Reductive Deamination by Benzyne for Deoxy Sugar Synthesis Through a Domino Reaction

Abstract

Benzyne was developed as a reducing agent in the key step of converting amino sugars and ketoses into deoxy sugars, which occur widely in natural products. Many deoxy sugars exhibit antibiotic and anticancer activities, and furthermore, they play essential biological roles. By treatment with CS2 and then Ac2O, amino sugars and ketoses were converted into the corresponding 1,3‐thiazolidine‐2‐thiones. In the key step, these intermediates were treated with 2‐trimethylsilylphenyl triflate (2.0 equiv.) and CsF (3.0 equiv.) in MeCN at 25 °C to produce acyclic enol acetates in 60–63 % yields. Saponification of the enol acetates with NaOMe/MeOH followed by intramolecular cyclization afforded the target 2‐deoxy sugars. The key step of the reductive deamination involved a domino 1,2‐elimination/[3+2]‐cycloaddition/retro [3+2]‐ring‐opening sequence. The generality of this new method was proven by the use of various substrates, including pentoses, hexoses, monosaccharides, disaccharides, aldoses, and ketoses.

The Quest for Novel Antimicrobial Compounds: Emerging Trends in Research, Development, and Technologies

“…BGC-like modularity may soon be commonplace in natural product synthesis. Recent advances in synthetic chemistry have widened the range of sugar nucleotides and deoxy sugars accessible [154,155]. Together, these developments have created opportunities to create synthetic antibiotics in known classes as also synthetic and semi-synthetic multi-hybrid antibiotics by assembling separate domains.…”

Domino Processes of Arynes Reacting with Three Classes of Nucleophiles for Organic Syntheses

“…Ghorai and Lee [3] publish a review article about aryne‐based multicomponent coupling reactions to produce arenes and heterocycles. Benzynes, the simplest members of arynes, are in an oxidized form from benzenes [4a,b,5] and generally function as oxidizing agents. In a few examples, benzynes can act as reducing agents [5] .…”

“…Benzynes, the simplest members of arynes, are in an oxidized form from benzenes [4a,b,5] and generally function as oxidizing agents. In a few examples, benzynes can act as reducing agents [5] . Application of arynes is still limited as harsh conditions are often required for their generation and thus complicate the sequential reactions to be carried out in situ [6] .…”

“…In a few examples, benzynes can act as reducing agents. [5] Application of arynes is still limited as harsh conditions are often required for their generation and thus complicate the sequential reactions to be carried out in situ. [6] Our laboratory plans to broaden the scope of arynes for their capability of reacting with neutral nucleophiles that contain an N-, S-, or O-atom under mild conditions.…”

Asymmetric Synthesis of 3‐Pyrrolines through an Aryne‐Induced Domino Process

“…[27,28] In addition to a review article of 2013 by Larock et al, [29] recent examples include a threecomponent coupling of benzyne in a carbopalladation reaction; [30] a three-component coupling reaction for the synthesis of benzofurans and coumarins; [31] sequential incorporation of CÀ S, CÀ N, and CÀ C bonds at three consecutive positions of arynes to form various 2,4-disubstituted benzothiazoles; [32] an aryne aza-Diels-Alder reaction and its application to synthesize isoquinolines; [33] conversion of sulfonamides to substituted 1,3-diaminobenzenes. [34] Arynes can also be used to induce the stereospecific olefination of βamino alcohols to alkenes, [35] deoxygenative olefination for the synthesis of deoxy and iminosugars, [36,37] silicon-controlled phenanthrene formation, [38] and a 1,2-addition/(3 + 2) dipolar cycloaddition between azomethine ylides and Schiff bases to yield imidazolidines. [39] The present study reports on the results of our development of a new domino reaction, which is described in Schemes 1 and 2.…”