Biologically Active 1-Aminodeoxy and 1-<i>O</i>-Alkyl Derivatives of The Powerful D-Glucosidase Inhibitor 2,5-Dideoxy-2,5-Imino-D-Mannitol

Wrodnigg, Tanja; Gaderbauer, Walter; Greimel, Peter; Häusler, Herwig; Sprenger, Friedrich; Stütz, Arnold; Virgona, Christopher T.; Withers, Stephen G.

doi:10.1080/07328300008544129

Cited by 22 publications

(11 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Azido alcohol 25 (Scheme 4) appeared to be a suitable choice,15 and after deprotonation with sodium hydride, the alkoxide reacted with mesylate 5 to give azido ether 26 in 89% yield 16. To install the C10 axial alcohol, the more electron-rich endocyclic double bond was first selectively dihydroxylated using Sharpless's asymmetric dihydroxylation conditions 7b,7e,17.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of (+)-Didemniserinolipid B: Application of a 2-Allyl-4-fluorophenyl Auxiliary for Relay Ring-Closing Metathesis

et al. 2008

View full text Add to dashboard Cite

The synthesis of didemniserinolipid B utilizing a ketalization/ring-closing metathesis (K/RCM) strategy is described. In the course of this work, a novel 2-allyl-4-fluorophenyl auxiliary for relay ring-closing metathesis (RRCM) was developed which increased the yield of the RCM. The resulting 6,8-dioxabicyclo[3.2.1]octene core was selectively functionalized by complimentary dihydroxylation and epoxidation routes to install the C10 axial alcohol. This bicyclic ketal core was further functionalized by etherification and an alkene cross metathesis with an unsaturated α-phenylselenyl ester en route to completing the total synthesis.

show abstract

Section: Resultsmentioning

confidence: 99%

Synthesis of (+)-Didemniserinolipid B: Application of a 2-Allyl-4-fluorophenyl Auxiliary for Relay Ring-Closing Metathesis

et al. 2008

View full text Add to dashboard Cite

show abstract

“…[10][11][12][13][14][15] They found that one-step N-derivatization of amine derivative 2 led to the generation of powerful β-glycosidase inhibitors, whereas aminoiminohexitol 2 itself was a moderate β-glucosidase inhibitor. [10,11,14] More recently, Ramesh and co-workers prepared several selective glycosidase inhibitors based on modifications to l-ido aza-sugar 3. [16] While the parent compound showed no glycosidase inhibitory activity, N-tosyl, N-methyl, and N-ethyl derivatives all exhibited good, and often selective, activity against the glycosidases tested.…”

Section: Introductionmentioning

confidence: 98%

Stereoselective Strecker and Carbamate Annulation Methodology for the Synthesis of 1‐Amino‐1,2,5‐trideoxy‐2,5‐imino‐L‐iditol

Win‐Mason

Dangerfield

Tyler³

et al. 2011

Eur J Org Chem

View full text Add to dashboard Cite

show abstract

“…Here, the Amadori rearrangement formed a key part of their synthetic strategy. [48][49][50][51][52][53] Stütz and Wrodnigg found that the one-step N-derivatisation of amine-derivative (12) led to the generation of powerful β-glycosidase inhibitors, while amino imino-hexitol 12 itself was a moderate β-glucosidase inhibitor. 48,49,52 More recently, Ramesh and co-workers prepared several selective glycosidase inhibitors based on modifications to the L-ido azasugar 13.…”

Section: Amino-imino-hexitols As Glycosidase Inhibitorsmentioning

confidence: 99%

“…[48][49][50][51][52][53] Stütz and Wrodnigg found that the one-step N-derivatisation of amine-derivative (12) led to the generation of powerful β-glycosidase inhibitors, while amino imino-hexitol 12 itself was a moderate β-glucosidase inhibitor. 48,49,52 More recently, Ramesh and co-workers prepared several selective glycosidase inhibitors based on modifications to the L-ido azasugar 13. 54 While the parent compound showed no glycosidase inhibitory activity, N-tosyl, N-methyl, and N-ethyl derivatives all exhibited good, and often selective, activity against the glycosidases tested.…”

Section: Amino-imino-hexitols As Glycosidase Inhibitorsmentioning

confidence: 99%

See 1 more Smart Citation

The Synthesis of Azasugars Using an I2-mediated Carbamate Annulation

Win‐Mason¹

View full text Add to dashboard Cite

<p>The biological activity of azasugars has largely been attributed to their ability to mimic the oxocarbenium ion-like transition state formed during reactions with carbohydrate-processing enzymes and, for this reason, functional and stereochemical modifications of the azasugar scaffold have led to the development of specific and potent glycosidase inhibitors. Given the potential of azasugars as glycosidase inhibitors, we were interested in developing efficient methodology for their synthesis. This thesis highlights synthetic methodology developed to produce amino-imino-hexitols as azasugar scaffolds. Key in the synthesis of the amino-imino-hexitols was the application of a stereoselective Strecker reaction, without the need for chiral Lewis acids or catalysts, and an extension of an I2-mediated carbamate annulation to cyclise functionalised and protected alkenylamines. Sixteen amino-imino-hexitols were synthesized, including ten previously undisclosed substrates with the D-galacto, D-talo, and L-altro configurations. The novel amino-imino-hexitols were then tested for their ability to act as glycosidase inhibitors and substrates of the D-talo configuration showed promising inhibitory effects. Mechanistic considerations of the I2-mediated carbamate annulation are discussed and although the exact annulation mechanism has yet to be determined, experimental studies have revealed that an aziridine is not an intermediate in the reaction. Factors influencing the diastereoselectivity of the carbamate annulation are also explored. Furthermore, an in depth analysis of the high cis-selectivity of the carbamate annulation is investigated using density functional theory to calculate the transition states of iodocyclisations en route to the formation of carbamates. Taken as a whole, the applicability of the carbamate annulation to a variety of alkenylamines and an understanding of the factors controlling the diastereoselectivity of the reaction should make this methodology a valuable addition to the synthetic chemist’s toolbox.</p>

show abstract

Biologically Active 1-Aminodeoxy and 1-O-Alkyl Derivatives of The Powerful D-Glucosidase Inhibitor 2,5-Dideoxy-2,5-Imino-D-Mannitol

Cited by 22 publications

References 14 publications

Synthesis of (+)-Didemniserinolipid B: Application of a 2-Allyl-4-fluorophenyl Auxiliary for Relay Ring-Closing Metathesis

Synthesis of (+)-Didemniserinolipid B: Application of a 2-Allyl-4-fluorophenyl Auxiliary for Relay Ring-Closing Metathesis

Stereoselective Strecker and Carbamate Annulation Methodology for the Synthesis of 1‐Amino‐1,2,5‐trideoxy‐2,5‐imino‐L‐iditol

The Synthesis of Azasugars Using an I2-mediated Carbamate Annulation

Contact Info

Product

Resources

About