A chemically contiguous hapten approach for a heroin–fentanyl vaccine
- Yoshihiro Natori,
- Candy S. Hwang,
- Lucy Lin,
- Lauren C. Smith,
- Bin Zhou and
- Kim D. Janda
Beilstein J. Org. Chem. 2019, 15, 1020–1031, doi:10.3762/bjoc.15.100
Graphical Abstract
Figure 1: Graphical summary of chemically contiguous opioid vaccine approach. A) Illustration of chemically c...
Figure 2: The chemically contiguous heroin–fentanyl haptens designed in this study. Grouping was based on the...
Figure 3: Heroin intermediates used to synthesize HF-1 through HF-9.
Scheme 1: General outline of HF-1, HF-2, HF-3, HF-7 synthesis from fentanyl intermediate 5 and heroin interme...
Scheme 2: Synthesis of fentanyl intermediate 5. Reaction conditions: a) phthalic anhydride, AcOH, reflux, 81%...
Scheme 3: General outline of HF-5, HF-8, HF-9 synthesis from fentanyl intermediates 28 and 46, and heroin int...
Scheme 4: Parallel synthesis of fentanyl domains 25 and 34, for HF-4 and HF-6, respectively.
Scheme 5: General strategy and coupling partners for the chemically contiguous series. aGeneral conditions fo...
Figure 4: Vaccination, titer assessment, and bleed schedule.
Figure 5: Summary of behavioral data for most promising chemically contiguous vaccine HF-7, compared to singu...
Figure 6: Summary of behavioral data for phenethyl-linked haptens HF-4 and HF-6. Bars represent mean ± SEM.
Figure 7: Correlation plots of dual hapten vaccines comparing week 5 and 8 ELISA midpoint titers to ED50 valu...
Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates
- Yuichi Yoshimura,
- Hideaki Wakamatsu,
- Yoshihiro Natori,
- Yukako Saito and
- Noriaki Minakawa
Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137
Graphical Abstract
Figure 1: Design of potential antineoplastic nucleosides.
Scheme 1: Synthesis of 4’-thioDMDC.
Scheme 2: Synthesis of 4’-thioribonucleosides by Minakawa and Matsuda.
Scheme 3: Synthesis of 4’-thioribonucleosides by Yoshimura.
Figure 2: Concept of the Pummerer-type glycosylation and hypervalent iodine-mediated glycosylation.
Scheme 4: Oxidative glycosylation of 4-thioribose mediated by hypervalent iodine.
Figure 3: Speculated mechanism of oxidative glycosylation mediated by hypervalent iodine.
Scheme 5: Synthesis of purine 4’-thioribonucleosides using hypervalent iodine-mediated glycosylation.
Scheme 6: Unexpected glycosylation of a thietanose derivative.
Scheme 7: Speculated mechanism of the ring expansion of a thietanose derivative.
Scheme 8: Synthesis of thietanonucleosides using the Pummerer-type glycosylation.
Scheme 9: First synthesis of 4’-selenonucleosides.
Scheme 10: The Pummerer-type glycosylation of 4-selenoxide 74.
Scheme 11: Synthesis of purine 4’-selenonucleosides using hypervalent iodine-mediated glycosylation.
Figure 4: Concept of the oxidative coupling reaction applicable to the synthesis of carbocyclic nucleosides.
Scheme 12: Oxidative coupling reaction mediated by hypervalent iodine.
Scheme 13: Synthesis of cyclohexenyl nucleosides using an oxidative coupling reaction.
Figure 5: Concept of the oxidative coupling reaction of glycal derivatives.
Scheme 14: Oxidative coupling reaction of silylated uracil and DHP using hypervalent iodine.
Scheme 15: Proposed mechanism of the oxidative coupling reaction mediated by hypervalent iodine.
Figure 6: Synthesis of 2’,3’-unsaturated nucleosides using hypervalent iodine and a co-catalyst.
Scheme 16: Synthesis of dihydropyranonucleoside.
Scheme 17: Synthesis of acetoxyacetals using hypervalent iodine and addition of silylated base.
Scheme 18: One-pot fragmentation-nucleophilic additions mediated by hypervalent iodine.
Figure 7: The reaction of thioglycoside with hypervalent iodine in the presence of Lewis acids.
Scheme 19: Synthesis of disaccharides employing thioglycosides under an oxidative coupling reaction mediated b...
Scheme 20: Synthesis of disaccharides using disarmed thioglycosides by hypervalent iodine-mediated glycosylati...
Scheme 21: Glycosylation using aryl(trifluoroethyl)iodium triflimide.
Figure 8: Expected mechanism of hypervalent iodine-mediated glycosylation with glycals.
Scheme 22: Synthesis of oligosaccharides by hypervalent iodine-mediated glycosylation with glycals.
Scheme 23: Synthesis of 2-deoxy amino acid glycosides.
Figure 9: Rationale for the intramolecular migration of the amino acid unit.
