Synthesis and Structural Revision of Glyphaeaside C

Byatt, Brendan J; Kato, Atsushi; Pyne, Stephen G.

doi:10.1021/acs.orglett.1c01248

Cited by 7 publications

(18 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Through total synthesis of its antipode we revised its structure to a derivative of 2,5-dideoxy-2,5imino-L-mannitol. [72] This revised L-DMDP-derived configuration is the first of its kind to be observed in Nature. The synthesis involved ring opening of the novel epoxide 113 with a Gilman-like diorganocopper reagent to give the alcohol 114 which upon a cross-metathesis reaction with 115 gave 116 as a 4.8:1 mixture of E and Z isomers, respectively.…”

Section: Synthesis and Structural Correction To Glyphaeaside Cmentioning

confidence: 78%

My 37 years of working with nitrogen heterocycles and alkaloids

Pyne

2022

Aust. J. Chem.

View full text Add to dashboard Cite

This account highlights work from my laboratory at the University of Wollongong (UOW), concerning nitrogen heterocycles and alkaloids, from my appointment as lecturer in Chemistry in February 1985 to the present time as an Emeritus Professor since 2022. I am thankful to the Royal Australian Chemical Institute for the recognition of my work through the recent award of a Distinguished Fellow at the national conference in Brisbane in July 2022.

show abstract

Section: Synthesis and Structural Correction To Glyphaeaside Cmentioning

confidence: 78%

My 37 years of working with nitrogen heterocycles and alkaloids

Pyne

2022

Aust. J. Chem.

View full text Add to dashboard Cite

show abstract

“…As electron-rich tertiary amines are known to suppress olefin metathesis reactions via coordination to ruthenium catalysts, the N -PMB group of 18 was oxidatively cleaved with CAN, and the resulting secondary amine was protected as N -Cbz carbamate 20 (Scheme ). Cross-metathesis of 20 with estragole derivative 21 using Grubbs’ first-generation catalyst afforded 1,2-disubstituted alkene 23 as an inseparable mixture of isomers ( E / Z ratio up to 4.6:1, combined yield up to 74%) . Hydrogenolysis/hydrogenation of E / Z - 23 over PdCl 2 afforded compound 24 as a trifluoroacetate salt after semipreparative RP-HPLC purification using a TFA-buffered solvent system in 16% yield.…”

Section: Resultsmentioning

confidence: 99%

“…Method A: Compounds 20 (50 mg, 0.0651 mmol) and 21 (43.8 mg, 0.195 mmol) were co-evaporated with DCE (3 × 1 mL) and dissolved in anhydrous CH 2 Cl 2 (1.0 mL). The solution was degassed by sonication under argon flow for 10 min, followed by the addition of Grubbs’ first-generation catalyst (13.4 mg, 0.0163 mmol).…”

Section: Methodsmentioning

confidence: 99%

“…In a previous publication, we corrected the structure of glyphaeaside C via the synthesis of the 6- C -alkylated DMDP derivative 11 , consequently rationalizing the inhibitory activity of the natural product against almond β-glucosidase and snail β-mannosidase as being consistent with that of several DMDP-based broussonetine alkaloids, − although the absolute configuration of the natural product could not be conclusively determined. In this work, we report the synthesis and glycosidase inhibitory activities of the originally purported structure of glyphaeaside C ( 10 ) and related α-1- C -alkylated DNJ derivatives to investigate their glycosidase inhibitory activities and to document their spectroscopic data, making future isolation studies, structure elucidations, and biological assays and SAR analysis more reliable .…”

mentioning

confidence: 99%

See 1 more Smart Citation

Synthesis of the Purported Structure of Glyphaeaside C and Proposed Revisions to the Structures of the Glyphaeaside Alkaloids

2023

Self Cite

View full text Add to dashboard Cite

The 10 glyphaeaside alkaloids isolated from the roots of Glyphaea brevis were originally purported as piperidine-based 1-C-alkylated iminosugars, with the A-, B-, and C-type glyphaeasides bearing l-DFJ, DGJ, and DNJ ring configurations, respectively. Subsequent investigations have revealed glyphaeaside C as being a pyrrolidine-based iminosugar with a DMDP ring configuration via total synthesis of the revised structure. In this work, side chain diastereomers of the originally purported structure of glyphaeaside C (10) and two related α-1-C-alkylated DNJ derivatives were synthesized from a common precursor, which was prepared in turn via stereoselective Grignard addition to a protected d-glycosylamine, followed by a reductive amination–cyclization sequence. Glycosidase inhibitory activity studies revealed general structure 10 as having potent inhibition against various α-glucosidases and weak inhibition against almond β-glucosidase in agreement with similar DNJ-based iminosugars and in contrast to natural glyphaeaside C, suggesting that the (1,2-dihydroxy-3-phenyl)propyl moiety does not play a particularly vital role in the inhibitory modes of action of either compound. Furthermore, the absolute configuration of natural glyphaeaside C was proposed as that of d-DMDP, and the structures of the A- and B-type glyphaeasides were revised as 1-deoxy-DALDP and DALDP derivatives, respectively, based on interpretation of their reported NMR spectroscopic data.

show abstract

“…Moreover, the total synthesis of glyphaeaside C revealed that its structure closely resembles that of 2,5-dideoxy-2,5-imino-D-mannitol (D-DMDP). In 2021, Byatt et al [ 38 ] reported the multi-step facile synthesis of glyphaeaside C. The total synthesis of our target molecule initiated with the synthesis of pyrrolidine fragments from readily available starting reagent, i.e., 2,3,5-tri-O-benzyl-β-D-arabinofuranose 26 . The fragments were then reacted to give oxazolidinone a and b.…”

Section: Review Of the Literaturementioning

confidence: 99%

Sharpless Asymmetric Dihydroxylation: An Impressive Gadget for the Synthesis of Natural Products: A Review

et al. 2023

View full text Add to dashboard Cite

Sharpless asymmetric dihydroxylation is an important reaction in the enantioselective synthesis of chiral vicinal diols that involves the treatment of alkene with osmium tetroxide along with optically active quinine ligand. Sharpless introduced this methodology after considering the importance of enantioselectivity in the total synthesis of medicinally important compounds. Vicinal diols, produced as a result of this reaction, act as intermediates in the synthesis of different naturally occurring compounds. Hence, Sharpless asymmetric dihydroxylation plays an important role in synthetic organic chemistry due to its undeniable contribution to the synthesis of biologically active organic compounds. This review emphasizes the significance of Sharpless asymmetric dihydroxylation in the total synthesis of various natural products, published since 2020.

show abstract

Synthesis and Structural Revision of Glyphaeaside C

Cited by 7 publications

References 26 publications

My 37 years of working with nitrogen heterocycles and alkaloids

My 37 years of working with nitrogen heterocycles and alkaloids

Synthesis of the Purported Structure of Glyphaeaside C and Proposed Revisions to the Structures of the Glyphaeaside Alkaloids

Sharpless Asymmetric Dihydroxylation: An Impressive Gadget for the Synthesis of Natural Products: A Review

Contact Info

Product

Resources

About