A [3+3] cyclization strategy for asymmetric synthesis of alkyl substituted piperidine-2-ones using 1,2-cyclic sulfamidates: a formal synthesis of (S)-coniine from l-norvaline

Combined Enzyme- and Transition Metal-Catalyzed Strategy for the Enantioselective Syntheses of Nitrogen Heterocycles: (−)-Coniine, DAB-1, and Nectrisine

“…The crude residue was purified using SiO 2 flash chromatography (16% EtOAc/hexanes). This material was further purified by radial silica gel chromatography (gradient; 100% hexanes to 5% EtOAc to 10% EtOAc in hexanes) to remove the cis isomer and afford 950 mg (87% yield) of 6b as colorless oil: 93% ee (OD-H Chiralcel HPLC column, 5% IPA in hexane, R t = 6.8 min, 8.8 min), 1 H NMR (300 MHz, 313 K, CDCl 3 ): δ 7.36−7.30 (m, 5H), 6.11 (dtd, J = 15.6, 5.0, 1.1 Hz, 1H), 5.93−5.86 (ddt, J = 15.6, 6.3, 1.2 Hz, 1H), 5.41 (dd, J = 6.3, 0.9 Hz, 1H), 4.53 (s, 2H), 4.25 (q, J = 7.1 Hz, 4H), 4.08 (d, J = 5.1 Hz, 2H), 1.31−1.27 (m, 6H); 13 (17). To a flame-dried 20 mL scintillation vial was added allylic azide 16 (575 mg, 2.09 mmol, 1.0 equiv) and anhydrous EtOH (10 mL, 0.1 M).…”

“…Coniine has a storied past in toxicology circles as the active poison of spotted hemlock and is known most notably for its role in the death of Socrates . Furthermore, the de novo chemical synthesis of coniine remains a touchstone for the synthesis of substituted piperidines. − DAB-1 ( 2 ) and nectrisine ( 3 ) are polyhydroxylated pyrrolidine iminosugars isolated from terrestrial sources. , DAB-1 is a potent inhibitor (IC 50 = 9.3 μM) against a specific glycosidase, rabbit muscle glycogen phosphorylase, while being mostly ineffective toward glycogen synthesis enzymes . Structurally related nectrisine ( 3 ) is also a strong inhibitor of α-glucosidases .…”

Novel peptidomimetic peptide deformylase (PDF) inhibitors of Mycobacterium tuberculosis

“…The reaction mixture was refluxed for 4 hr. After cooling, equal quantity of toluene (150 ml) was added and all volatiles were removed using rotary evaporator to yield solid L-valine ethyl ester hydrochloride (Karanfil, Balta, & Eskici, 2012).…”

Synthesis of Acyclic and Cyclic Sulfamates: A Review

“…One of the most useful methods for the synthesis of five-and six-membered cyclic sulfamates is from β-amino alcohols and γ-amino alcohols. [71][72][73][74][75][76][77] Treatment of amino alcohols with thionyl chloride and subsequently oxidation of the prepared sulfamidite with sodium periodate in the presence of ruthenium trichloride as a catalyst in aqueous acetonitrile [78][79][80] or aqueous ethyl acetate, 81,82 resulted in the formation of the corresponding cyclic sulfamates 50 in high yield (Table 3). 81 It should be noted that the cyclic sulfamates can be used for the synthesis of amines.…”