First and Highly Stereoselective Synthesis of Both Enantiomers of Octahydroindole‐2‐phosphonic Acid (Oic^P)

Abstract

We report the first stereoselective synthesis of (2R,3aR,7aR)‐ and (2S,3aS,7aS)‐octahydroindole‐2‐phosphonic acid 2 (OicP derivatives). The key points are the highly diastereoselective synthesis of cis‐fused bicyclic (3aR,7aR)‐ and (3aS,7aS)‐pyrrolidin‐2‐ones 4 through a dynamic kinetic resolution of racemic γ‐keto acid (±)‐5 with (R)‐ and (S)‐phenylglycinol via Meyers' bicyclic lactams, and the highly diastereoselective addition of trimethyl phosphite to the N‐acyliminium ions 3 obtained from 4.

Acyclic Twisted Amides

“…Similar to β-lactams, the amide bond geometry of structurally characterized amides embedded in a fused five-membered ring system (Figures –) − ,− can be characterized as N-pyramidalized (average χ N of 45.9°) with minimal twist (average τ of 11.7°). As expected, the average values of N-pyramidalization and twist are slightly lower as compared to β-lactams ...…”

Discovery of Octahydroisoindolone as a Scaffold for the Selective Inhibition of Chitinase B1 from Aspergillus fumigatus: In Silico Drug Design Studies

“…We found the molecular geometry of the oxazolinium ion in its minimum energy conformation with dihedral angles of φ1 = 8.75°, θ1 = 105.82° (O4-C3a-O3) and θ2 = 110.03° (C7-C7a-N1), which were similar to the allosamizoline conformation. On the other side, scaffold design was performed on the basis of reliable synthetic methods, like those described in Meyers's lactams synthesis for the preparation of cis-and trans-fused lactams [47][48][49]. As a result, from conformational analysis in comparison to oxazolinium ion and allosamizoline moiety, only in Figure 7, the cis-fused scaffolds and their enantiomers had similar angles (Table S26, see Supplementary Data).…”

“…Further, φ1, θ1, and θ2 angles indicate similar amide orientation in scaffolds, as oxazole shows in the structure references. On the other side, scaffold design was performed on the basis of reliable synthetic methods, like those described in Meyers's lactams synthesis for the preparation of cisand trans-fused lactams [47][48][49]. As a result, from conformational analysis in comparison to oxazolinium ion and allosamizoline moiety, only in Figure 7, the cis-fused scaffolds and their enantiomers had similar angles (Table S26, see Supplementary Data).…”

“…For this set analysis we employed a rigid docking approach; hence, Figure 10 shows the scaffold derivatives design that consisted of the substitution in the C-3 position, because the access to enantiomerically pure compounds was rationalized by a nucleophilic attack via the acyliminium ion as a reaction intermediate furnishing the substituted lactams [48,54]. The first design step explored the functional groups effect by placing hydrocarbon chains by one to three carbons, and bound to functional groups like amines, thiols, alcohols, or carboxylic acids (group I).…”

Convenient access to pyrrolidin-3-ylphosphonic acids and tetrahydro-2H-pyran-3-ylphosphonates with multiple contiguous stereocenters from nonracemic adducts of a Ni(II)-catalyzed Michael reaction

“…These circumstances create an interest in discovering synthetic routes for obtaining nonracemic phosphoryl-substituted hetero- cycles. Thus, in recent years, effective methods for the asymmetric synthesis of chiral phosphonates containing octahydroindole [10], tetrahydroquinoline [11], tetrahydroisoquinoline [11,12], β-carboline [13], morpholine [14], and isoindoline [15] moieties have been developed. Obtained in an enantiomerically pure form, phosphonoproline and its analogues [16][17][18][19] were among the first compounds in this series.…”