A Chiron Approach to Diversity-Oriented Synthesis of Aminocyclitols, (−)-Conduramine F-4 and Polyhydroxyaminoazepanes from a Common Precursor

Abstract

The total syntheses of aminocyclitols, (-)-conduramine F-4, and polyhydroxyaminoazepanes have been achieved from a common precursor derived from tri-O-benzyl-d-glucal through a 'diversity-oriented' approach. Tri-O-benzyl-d-glucal was converted into a protected 1,6-diol through a sequence of steps that include transformation to a 2-tosylamidoglucose derivative, selective deprotection of primary C-6 benzyloxy group, LiAlH-mediated one-step reduction of acetate groups, and reductive ring opening of the resulting hemiacetal as the key steps. The 1,6-diol served as a common precursor in our diversity oriented approach toward the target molecules. Mesylation of the diol followed by double nucleophilic substitution reaction with primary amines led to the synthesis of amino-substituted polyhydroxyazepanes. On the other hand, dialdehyde obtained from the oxidation of 1,6-diol was found to be a convenient starting material for the synthesis of aminocyclitols and (-)-conduramine F-4. McMurry coupling of the dialdehyde was successfully employed, for the first time, to construct the carbocyclic framework of aminoyclitols, while bis-Wittig olefination of the dialdehyde followed by Grubb's(II)-catalyzed RCM delivered (-)-conduramine F-4. The stereochemistry of newly created chiral centers in aminocyclitols was established through single crystal X-ray crystallography and detailed NOE studies.

Asymmetric syntheses of four stereoisomers of 13‐hydroxy‐14‐methylhexadecanoic acid as potential antibacterial agents

“…The data that support the findings of this study are openly available in figshare at http://doi.org/10.1002/chir.23352, reference number [1–43].…”

“…The unsaturated C‐C bonds were hydrogenated completely with PtO 2 , 29 and the following hydrolysis with KOH and acid‐catalyzed lactonization afforded the mixtures of chiral lactones 4a and 4b (dr 1:1.27, determined by 1 H NMR) 30 . The two chiral lactones were isolated by preparative thin layer chromatography, and the absolute configuration of the newly formed chiral center of 4a was confirmed as ( S ) due to the NOE effects observed between the hydrogens of methyl at C‐3 and H‐4 31,32 . Therefore, the stereochemistry of 4a was (3 S , 4 R ), and that of its diastereomer 4b was (3 R , 4 R ), which was consistent with the analysis of vibrational circular dichroism (VCD) 33 …”

Enantioselective Synthesis of the Sex Pheromone of Lichen Moth, Miltochrista calamine, and Its Diastereomer

“…The stereochemistry of new chiral center of 12a at C-7 was assigned as S due to NOE effect observed between H-7 and the hydrogens of methyl at C-5. 24,25 Therefore, the configuration of its diastereomer 12b was 5R,7R. Furthermore, the comparison of the chemical shifts of the protons (Δ H =  S - R ) between the (S)-and (R)-MTPA of 12a also suggested its S configuration at C-7; meanwhile the stereochemistry of MTPA ester 12b at C-7 was also confirmed as R via analysis of the difference in 1 H chemical shifts (Δ H =  S - R ) between its (S)-and (R)-MTPA Mosher esters (Figure 2).…”

Design and synthesis of glycomimetics: Recent advances

“…Among recently reported carbasugars, a new protocol for the synthesis of aminocyclitols was proposed by Harit et al in 2016, based on a McMurry pinacol coupling reaction, as shown in the retrosynthetic scheme reported in Figure . The amino‐carbasugar structural motif of aminocyclitols is particularly important since it is found in a variety of biologically active compounds like aminoglycoside antibiotics and alkaloids .…”