A Concise Synthesis of (2R,3R)‐ and (2R,3S)‐3‐Hydroxypipecolic Acids, and Total Synthesis of (–)‐Deoxoprosopinine and (+)‐2‐epi‐Deoxoprosopinine from D‐Glycals

Abstract

Short and efficient formal syntheses of (2R,3R)‐ and (2R,3S)‐3‐hydroxypipecolic acids, and total syntheses of (–)‐deoxoprosopinine and (+)‐2‐epi‐deoxoprosopinine have been achieved starting from D‐glycals. The key steps involved in these syntheses were Ferrier rearrangement, azide reduction, intramolecular cyclization, and Grignard reaction.

Cutting-Edge and Time-Honored Strategies for Stereoselective Construction of C–N Bonds in Total Synthesis

“…At the same time, the pyrrolidine fragment was assembled from d -arabinose utilizing diastereoselective addition of Grignard reagent to nitrone 48 - 3 . Similarly, the heterocyclic cores of several relatively simple piperidine and pyrrolidine natural products, including fagomine derivatives, deoxoprosopine, and swainsonine, were assembled by the reaction between 1,4- or 1,5-disulfonates and primary amines. During the synthesis of the anticancer agent piperazimycin A, Ma and co-workers demonstrated that the nucleophilic substitution of sulfonate with hydrazine as a source of nitrogen can also be useful for the installation of the chiral center of the α-substituted hexahydropyridazine ring …”

Bisnucleophilic Substitution as a Synthetic Tool for Ready Access to the Piperidine Alkaloids (+)-Connine, (+)-β-Conhydrine, (+)-8-Ethylnorlobelol, and (–)-Halosaline

“…Having diols 7a-d in hand, these were converted into their corresponding dimesylates under conventional conditions (MsCl, Et 3 N, CH 2 Cl 2 , 0 °C, 2 h) to furnish the desired precursors 5a (91%), 5b (90%), 5c (92%), 5d (89%, Scheme 6). The dimesylates 5a-d were subjected to bisnucleophilic substitution 13 with benzlamine independently to afford the benzyl-protected piperidines 27a (92%), 27b (95%), 27c (94%), and 27d (91%).…”

Concise and Straightforward Asymmetric Synthesis of a Cyclic Natural Hydroxy-Amino Acid

“…These compounds are β-turn inducers in the synthesis of peptides [4] and good enzyme inhibitors by themselves [5] as are several of their derivatives, such as deoxy-galactono-jirimicin derivatives [6,7,8]. Indeed, stereoselective synthesis of hydroxy-amino acids is a field that has been growing during the last decades because of the potential biological activity of some representatives of this class of compounds, mainly as enzyme inhibitors [5,9,10,11,12]. Particularly, conformationally constrained hydroxy-amino acids such as the hydroxylated pipecolic acids are very interesting target molecules [12,13].…”

“…Indeed, stereoselective synthesis of hydroxy-amino acids is a field that has been growing during the last decades because of the potential biological activity of some representatives of this class of compounds, mainly as enzyme inhibitors [5,9,10,11,12]. Particularly, conformationally constrained hydroxy-amino acids such as the hydroxylated pipecolic acids are very interesting target molecules [12,13]. For instance, the compound (2 S ,4 R )-4-hydroxy-pipecolic acid is a natural product that has been isolated from Calliandra pittieri and Stophantus scandeus [14], and the cis -5-hydroxy-substituted pipecolic acid skeleton is frequently found in alkaloids from microorganisms and also in plants (febrifugine, pseudoconhidrine) [15,16].…”