Metathesis access to monocyclic iminocyclitol-based therapeutic agents

Abstract

SummaryBy focusing on recent developments on natural and non-natural azasugars (iminocyclitols), this review bolsters the case for the role of olefin metathesis reactions (RCM, CM) as key transformations in the multistep syntheses of pyrrolidine-, piperidine- and azepane-based iminocyclitols, as important therapeutic agents against a range of common diseases and as tools for studying metabolic disorders. Considerable improvements brought about by introduction of one or more metathesis steps are outlined, with emphasis on the exquisite steric control and atom-economical outcome of the overall process. The comparative performance of several established metathesis catalysts is also highlighted.

Conformationally-Locked N-Glycosides with Selective β-Glucosidase Inhibitory Activity: Identification of a New Non-Iminosugar-Type Pharmacological Chaperone for Gaucher Disease

“…(q, 2H, J = 7.6 Hz), 1.53 (q, 2H, J = 6.8 Hz), 1.42−1.23 (m, 26H). 13 (24). The title compound was prepared following the general procedure for acetyl deprotection of cis-1,2-fused 1,3-oxazoline carbohydrate derivatives starting from 14 (100 mg, 0.23 mmol), MeONa (6.8 mg, 12 μmol), and MeOH (4.6 mL).…”

Substrate‐Regiocontrolled Synthesis of Enantioenriched Allylic Amines by Palladium‐Catalysed Asymmetric Allylic Amination: Formal Synthesis of Fagomine

“…Asymmetric syntheses employing these intermediates could lead to discovery of further biologically relevant piperidine/azepane alkaloids and imino sugars. [35] The key intermediate 24 was thus first obtained using the (R,R)-DACH naphthyl ligand under standard conditions in 91% yield and 94% ee. After assessing the high degree of regio-and stereoselectivity of this reaction, the crude compound 24 obtained by reaction of 2a with 23 was directly subjected to ring closing metathesis under Wrights conditions, [36] using 5 mol% of Grubbss second generation catalyst in the presence of one equivalent of p-toluenesulfonic acid …”

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

“…In 2010, Ramharter and Mulzer [83] prepared an intricate tricyclic intermediate useful for the total synthesis of the alkaloid (+)-lycoflexine (15). In this strategy, first a protected dienyne precursor was prepared that, by an enyne tandem ringclosing metathesis induced by the Grubbs second-generation Ru catalyst, produced a tricyclic diene in 52% yield.…”

“…Alkene and alkyne metathesis [1][2][3][4], constituting highly versatile and powerful catalytic processes for constructing complex organic molecules [5][6][7][8][9][10][11][12], have found broad application in the fields of pharmaceutical synthesis [13][14][15], materials science [16][17][18][19][20], or in advanced techniques and technologies [21][22][23][24][25][26][27][28][29][30]. Thus, numerous multistep total syntheses of organic compounds, including bioactive molecules [31][32][33][34][35] and natural products [36,37], have been performed in a highly chemo-and stereoselective manner through metathesis routes [38][39][40][41][42][43].…”